Chapter 1: Nutrition and You

Adapted from: Zimmerman and Snow. “An Introduction to Nutrition” v. 1.0. Accessed on December 4, 2017. https://2012books.lardbucket.org/books/an-introduction-to-nutrition/

Also includes selected sections from: Lindshield, B. L. Kansas State University Human Nutrition (FNDH 400) Flexbook. Accessed on December 4, 2017. goo.gl/vOAnR

As we get started on our journey into the world of health and nutrition, our first focus will be to demonstrate that nutritional science is an evolving field of study, continually being updated and supported by research, studies, and trials.

Sections:

Let’s begin with a story: the story of peptic ulcers and H. pylori.

Peptic ulcers are painful sores in the gastrointestinal tract. Symptoms of peptic ulcers include abdominal pain, nausea, loss of appetite, and weight loss. The cure for this ailment took some time for scientists to figure out. If your grandfather complained to his doctor of symptoms of peptic ulcer, he was probably told to avoid spicy foods, alcohol, and coffee, and to manage his stress. In the early twentieth century, the medical community thought peptic ulcers were caused by what you ate and drank, and by stress.

Image source: https://www.gicare.com/diseases/peptic-ulcer/

In 1915, Dr. Bertram W. Sippy devised the “Sippy diet” for treating peptic ulcers. Dr. Sippy advised patients to drink small amounts of cream and milk every hour in order to neutralize stomach acid. Ultimately, the Sippy diet did not cure peptic ulcers and in the latter 1960s, scientists discovered the diet was associated with a significant increase in heart disease due to its high saturated fat content.

In the 1980s, Australian physicians Barry Marshall and Robin Warren proposed a radical hypothesis — that the cause of ulcers was bacteria that could survive in the acidic environment of the stomach and small intestine¹. They met with significant opposition to their hypothesis but they persisted with their research. Their research led to an understanding that the spiral shape of the bacterium Helicobacter pylori (H. pylori) allows it to penetrate the stomach’s mucous lining, where it secretes an enzyme that generates substances to neutralize the stomach’s acidity. This weakens the stomach’s protective mucous, making the tissue more susceptible to the damaging effects of acid, leading to the development of sores and ulcers. H. pylori also prompt the stomach to produce even more acid, further damaging the stomach lining

In 1994, the National Institutes of Health held a conference on the cause of peptic ulcers. There was scientific consensus that H. pylori cause most peptic ulcers and that patients should be treated with antibiotics.

In 1996, the Food and Drug Administration (FDA) approved the first antibiotic that could be used to treat patients with peptic ulcers. Nevertheless, the link between H. pylori and peptic ulcers was not sufficiently communicated to health-care providers. In fact, 75 percent of patients with peptic ulcers in the late 1990s were still being prescribed antacid medications and advised to change their diet and reduce their stress.

In 1997, the Centers for Disease Control and Prevention (CDC), alongside other public health organizations, began an intensive educational campaign to convince the public and health-care providers that peptic ulcers are a curable condition requiring treatment with antibiotics. Today, if you go to your primary physician you will be given the option of taking an antibiotic to eradicate H. pylori from your gut.

The H. pylori discovery was made recently, overturning a theory applied in our own time. The demystification of disease requires the continuous forward march of science, overturning old, traditional theories and discovering new, more effective ways to treat disease and promote health. In 2005, Marshall and Warren were awarded the prestigious Nobel Prize in medicine for their discovery that many stomach ulcers are caused by H. pylori.

A primary goal of this text is to provide you with information backed by nutritional science, and with a variety of resources that use scientific evidence to optimize health and prevent disease. In this chapter, you will see that there are many conditions and deadly diseases that can be prevented by good nutrition. You will also discover the many other determinants of health and disease, how the powerful tool of scientific investigation is used to design dietary guidelines, and recommendations that will promote health and prevent disease.

“The most exciting phrase to hear in science, the one that heralds new discoveries, is not ‘Eureka!’ but ‘That’s funny...’”

- Isaac Asimov (January 2, 1920–April 6, 1992)

References & Links

1Marshall and Warren. “Ulcers — The Culprit Is H. Pylori!” National Institutes of Health, Office of Science Education. Accessed on November 10, 2011. http://science.education.nih.gov/home2.nsf/Educational+ResourcesResource+FormatsOnline+Resources+High+Sc hool/928BAB9A176A71B585256CCD00634489

Your View of Food

Americans are bombarded with television programs that show where to find the best dinners, pizzas, and cakes, and the restaurants that serve the biggest and juiciest burgers. Other programs feature chefs battling to prepare meals, and the top places to burst your belly from consuming atomic chicken wings and deli sandwiches longer than a foot. There are also shows that feature bizarre foods from cultures around the world. How do you use the information from popular network food shows to build a nutritious meal? You don’t — these shows are for entertainment. The construction of a nutritious meal requires learning about which foods are healthy and which foods are not, how foods and nutrients function in your body, and how to use scientific resources. This text is designed to provide you with the information necessary to make sound nutritional choices that will optimize health and help prevent disease.

How do you fill your plate? © Shutterstcock

The word nutrition first appeared in 1551 and comes from the Latin word nutrire, which means, “to nourish.” Today, we define nutrition as the sum of all processes involved in how organisms obtain nutrients, metabolize them, and use them to support all of life’s processes. Nutritional science is the investigation of how an organism is nourished, and incorporates the study of how nourishment affects personal health, population health, and planetary health. Nutritional science covers a wide spectrum of disciplines. As a result, nutritional scientists can specialize in

particular aspects of nutrition such as biology, physiology, immunology, biochemistry, education, psychology, sustainability, and sociology.

Without adequate nutrition, the human body does not function optimally, and severe nutritional inadequacy can lead to disease and even death. The typical American diet is lacking in many ways, from not containing the proper amounts of essential nutrients, to being too speedily consumed, to being only meagerly satisfying. Dietitians are nutrition professionals who integrate their knowledge of nutritional science into helping people achieve a healthy diet and develop good dietary habits. The Academy of Nutrition and Dietetics (AND) is the largest organization of nutrition professionals worldwide and dietitians registered with the AND are committed to helping Americans eat well and live healthier lives. To learn more from the AND’s nutritional advice, visit http://www.eatright.org.

Nutrition, Health, and Disease

Your ability to wake up, to think clearly, to communicate, to hope, to dream, to go to school, to gain knowledge, to go to work, to earn a living, and to do all of the things that you like to do are dependent upon one factor—your health. Good health means you are able to function normally and work hard to achieve your goals in life. In 1946, the World Health Organization (WHO) defined health as “a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity.”¹

This definition was adopted into the WHO constitution in 1948 and has not been amended since. A triangle is often used to depict the equal influences of physical, mental, and social well- being on health (Figure 1.1).

Figure 1.1 The Health Triangle.

Disease is defined as any abnormal condition affecting the health of an organism, and is characterized by specific signs and symptoms. Signs refer to identifying characteristics of a disease such as swelling, weight loss, or fever. Symptoms are the features of a disease recognized by a patient and/or their doctor. Symptoms can include nausea, fatigue, irritability, and pain. Diseases are broadly categorized as resulting from pathogens (i.e., bacteria, viruses, fungi, and parasites), deficiencies, genetics, and physiological dysfunction. Diseases that primarily affect physical health are those that impair body structure (as is the case with osteoporosis), or functioning (as is the case with cardiovascular disease). The most effective and affordable method of preventing chronic disease starts with optimal nutrition.

Required Web Link

Mission Critical Health - Chronic Disease Nutrition

The foods we eat affect all three aspects of our health. For example, a teen with Type 2 diabetes (a disease brought on by poor diet) is first diagnosed by physical signs and symptoms such as increased urination, thirstiness, and unexplained weight loss. However, research has also found that teens with Type 2 diabetes have impaired thinking and do not interact well with others in school, thereby affecting mental and social wellbeing. Type 2 diabetes is just one example of a physiological disease that affects all aspects of health—physical, mental, and social.

Public Health and Disease Prevention

In 1894, the first congressional funds were appropriated to the US Department of Agriculture (USDA) for the study of the relationship between nutrition and human health. Dr. Wilbur Olin Atwater was appointed as the Chief of Nutrition Investigations and is recognized as the “Father of Nutrition Science” in America.²

Under his guidance, the USDA released the first bulletin to the American public that contained information on the amounts of fat, carbohydrates, proteins, and food energy in various foods. Nutritional science advanced considerably in these early years, but it took until 1980 for the USDA and the US Department of Health and Human Services (HHS) to jointly release the first edition of Nutrition and Your Health: Dietary Guidelines for Americans.

Although wide distribution of dietary guidelines did not come about until the 1980s, many historical events that demonstrated the importance of diet to health preceded their release. Assessments of the American diet in the 1930s led President Franklin D. Roosevelt to declare in his inaugural address on January 20, 1937, “I see one-third of our nation is ill-housed, ill-clad, and ill-nourished.” From the time of Atwater until the onset of the Great Depression nutritional scientists had discovered many of the vitamins and minerals essential for the functioning of the human body. Their work and the acknowledgement by President FDR of the nutritional inadequacy of the American diet evoked a united response between scientists and government leading to the enrichment of flour, the development of school lunch programs, and advancements of nutritional education in this country.

In the latter part of the twentieth century nutritional scientists, public health organizations, and the American public increasingly recognized that eating too much of certain foods is linked to chronic diseases. We now know that diet-related conditions and diseases include hypertension (high blood pressure), obesity, Type 2 diabetes, cardiovascular disease, some cancers, and osteoporosis. These diet-related conditions and diseases are some of the biggest killers of Americans. The HHS reports that unhealthy diets and inactivity cause between 310,000 and 580,000 deaths every single year.³

According to the USDA, eating healthier could save Americans over $70 billion per year and this does not include the cost of obesity, which is estimated to cost a further $117 billion per year. Unfortunately, despite the fact that the prevalence of these diseases can be decreased by healthier diets and increased physical activity, the CDC reports that the federal government spends one thousand times more to treat disease than to prevent it ($1,390 versus $1.21 per person each year).⁴

In 2010, the new edition of the dietary guidelines identified obesity as the number one nutritional-related health problem in the United States and established strategies to combat its incidence and health consequences in the American population. A 2008 study in the journal Obesity reported that if current trends are not changed, 100 percent of Americans will be overweight or obese in 2048!⁵

In 2011, the US federal government released a new multimedia tool that aims to help Americans choose healthier foods from the five food groups (grains, vegetables, fruits, dairy, and proteins). The tool, called “Choose MyPlate,” (Figure 1.2) is available at choosemyplate.gov. Whether at home or on-the-go, MyPlate can help you find a healthy eating style that works for you. (Watch Video 1.1).

Figure 1.2 The Federal Government’s New and Improved Tool of Nutritional Communication

Required Video 1.1

The U.S. Department of Agriculture’s Center for Nutrition Policy and Promotion introduces the “MyPlate, MyWins” video series that shows how small changes to what you eat and drink add up.

https://youtu.be/j7CcaUZrUoE

Rate My Plate Game

References & Links

1World Health Organization. Preamble to the Constitution of the World Health Organization as adopted by the International Health Conference, New York, June 19–July 22, 1946. http://www.who.int/suggestions/faq/en/

2Combs, G.F. “Celebration of the Past: Nutrition at USDA.” J Nutr 124, no. 9 supplement (1994): 1728S–32S. http://jn.nutrition.org/content/124/9_Suppl/1728S.long

3Center for Science in the Public Interest. “Nutrition Policy.” Accessed March 1, 2012. http://www.cspinet.org/nutritionpolicy/nutrition_policy.html#disease

4Combs, G.F. “Celebration of the Past: Nutrition at USDA.” J Nutr 124, no. 9 supplement (1994): 1728S–32S. http://jn.nutrition.org/content/124/9_Suppl/1728S.long

5Wang Y, et al. “Will All Americans Become Overweight or Obese? Estimating the Progression and Cost of the US

Obesity Epidemic.” Obesity 10, no. 16 (October 2008): 2323–30. http://www.nature.com/oby/journal/v16/n10/full/oby2008351a.html

What’s in Food?

The foods we eat contain nutrients. Nutrients are substances required by the body to perform its basic functions. Nutrients must be obtained from diet, since the human body does not synthesize them. Nutrients are used to produce energy, detect and respond to environmental surroundings, move, excrete wastes, respire, (breathe), grow, and reproduce. There are six classes of nutrients required for the body to function and maintain overall health (Figure 1.3). These are carbohydrates, lipids, proteins, water, vitamins, and minerals. Foods also contain non-nutrients that may be harmful (such as cholesterol, dyes, and preservatives) or beneficial (such as antioxidants). Non-nutrient substances in food will be further explored in later chapters.

Image Source: https://i0.wp.com/asc-spacebook.weebly.com/uploads/2/3/0/7/23071160/8313087.jpg.

Figure 1.3 The Six Essential Nutrients.

MACRONUTRIENTS

Nutrients that are needed in large amounts are called macronutrients. There are three classes of macronutrients: carbohydrates, lipids, and proteins (Figure 1.4). These can be metabolically processed into cellular energy. The energy from macronutrients comes from their chemical bonds. This chemical energy is converted into cellular energy that is then utilized to perform work, allowing our bodies to conduct their basic functions. A unit of measurement of food energy is the calorie. On nutrition food labels, the amount given for “calories” is actually

equivalent to each calorie multiplied by one thousand. A kilocalorie (one thousand calories, denoted with a small “c”) is synonymous with the “Calorie” (with a capital “C”) on nutrition food labels. Water is also a macronutrient in the sense that you require a large amount of it, but unlike the other macronutrients it does not yield calories.

Figure 1.4 The Macronutrients: Carbohydrates, Lipids, Protein, and Water.

Carbohydrates

Carbohydrates are molecules composed of carbon, hydrogen, and oxygen in a 1:2:1 ratio. The major food sources of carbohydrates are grains, milk, fruits, and starchy vegetables like potatoes. Non-starchy vegetables also contain carbohydrates, but in lesser quantities.

Carbohydrates are broadly classified into two forms based on their chemical structure: fast- releasing carbohydrates, often called simple sugars, and slow-releasing carbohydrates.

Fast-releasing carbohydrates consist of one or two basic units. Examples of simple sugars include sucrose, the type of sugar you would have in a bowl on the breakfast table, and glucose, the type of sugar that circulates in your blood.

Slow-releasing carbohydrates are long chains of simple sugars that can be branched or unbranched. During digestion, the body breaks down all slow-releasing carbohydrates to simple sugars, mostly glucose. Glucose is then transported to all our cells where it is stored, used to make energy, or used to build macromolecules. Fiber is also a slow-releasing carbohydrate, but it cannot be broken down in the human body and passes through the digestive tract undigested unless the bacteria that inhabit the gut break it down.

In addition to providing energy and serving as building blocks for bigger macromolecules, carbohydrates are essential for proper functioning of the nervous system, heart, and kidneys. As mentioned, glucose can be stored in the body for future use. In humans, the storage molecule of carbohydrates is called glycogen and in plants, it is known as starches. Glycogen and starches are slow-releasing carbohydrates.

Lipids

Lipids are also a family of molecules composed of carbon, hydrogen, and oxygen, but unlike carbohydrates, they are insoluble in water. Lipids are found predominately in butter, oils, meats, dairy products, nuts, and seeds, and in many processed foods. The three main types of lipids are triglycerides (triacylglycerol), phospholipids, and sterols. The main job of lipids is to store energy. Lipids provide more energy per gram than carbohydrates (nine kilocalories per gram of lipids versus four kilocalories per gram of carbohydrates). In addition to energy storage, lipids serve as cell membranes, surround and protect organs, aid in temperature regulation, and regulate many other functions in the body.

Proteins

Molecules composed of chains of amino acid subunits are called proteins. Amino acids in turn, are simple subunits composed of carbon, oxygen, hydrogen, and nitrogen. The food sources of proteins are meats, dairy products, seafood, and a variety of different plant-based foods, most notably soy. The word protein comes from a Greek word meaning “of primary importance,” which is an apt description of these macronutrients. Proteins provide four kilocalories of energy per gram; however, providing energy is not protein’s most important function. Proteins provide structure to bones, muscles and skin, and play a role in conducting most of the chemical reactions that take place in the body. Scientists estimate that greater than one-hundred thousand different proteins exist within the human body.

WATER

There is one other nutrient that we must have in large quantities: water. Water does not contain carbon, but is composed of two hydrogens and one oxygen per molecule of water. More than 60 percent of your total body weight is water. Without it, nothing could be transported in or out of the body, chemical reactions would not occur, organs would not be cushioned, and body temperature would fluctuate widely. According to the “rule of threes,” a generalization supported by survival experts, a person can survive three minutes without oxygen, three days without water, and three weeks without food. Since water is so critical for life’s basic processes, the amount of water input and output is supremely important.

MICRONUTRIENTS

Micronutrients are nutrients required by the body in lesser amounts, but are still essential for carrying out bodily functions. Micronutrients include all the essential minerals and vitamins. There are sixteen essential minerals and thirteen vitamins (See Table 1.1 "Minerals and Their Major Functions" and Table 1.2 "Vitamins and Their Major Functions" for a complete list and their major functions). In contrast to the macronutrients, the micronutrients are not directly used for making energy, but they assist in the process as being part of enzymes (i.e., coenzymes). Enzymes are proteins that catalyze chemical reactions in the body and are involved in all aspects of body functions from producing energy, to digesting nutrients, to building macromolecules. Micronutrients play many roles in the body.

Minerals

Minerals are solid inorganic substances that form crystals and are classified depending on how much of them we need. Trace minerals such as zinc, iron, or iodine are only required in a few milligrams or less per day. While major minerals such as calcium, sodium, and potassium are required in hundreds of milligrams per day. Many minerals are critical for enzyme function, others are used to maintain fluid balance, build bone tissue, synthesize hormones, transmit nerve impulses, contract and relax muscles, and protect against harmful free radicals.

Table 1.1 Minerals and Their Major Functions

Vitamins

Unlike minerals, vitamins are all organic compounds. The thirteen vitamins are categorized as either water-soluble or fat-soluble. The water-soluble vitamins are vitamin C and all the B vitamins. The fat-soluble vitamins are A, D, E, and K. Vitamins are required to perform many functions in the body such as making red blood cells, synthesizing bone tissue, and playing a role in normal vision, nervous system function, and immune system function. Vitamin deficiencies can cause severe health problems. For example, a deficiency in niacin causes pellagra. Until scientists found out that better diets relieved the signs and symptoms of pellagra, many people with the disease ended up in insane asylums awaiting death (Watch Video 1.2). Other vitamins were also found to prevent certain disorders and diseases such as scurvy (vitamin C), night blindness (vitamin A), and rickets (vitamin D).

Required Video 1.2

Pellagra: This video provides a brief history of Dr. Joseph Goldberger’s discovery that pellagra was a diet-related disease.

https://youtu.be/ZB_Yg9rrnSE

Table 1.2 Vitamins and Their Major Functions

Food Energy

Food energy is measured in kilocalories (kcals), commonly referred to as Calories. This terminology is technically incorrect, but is used so commonly that we will refer to them as calories throughout the course. A kilocalorie is the amount of energy needed to raise 1 kilogram of water 1 degree Celsius. A food’s kilocalories are determined by putting the food into a bomb calorimeter and determining the energy output (energy = heat produced). The link below is to a video of a bomb calorimeter showing how one is used (Watch Video 1.3).

Required Video 1.3

This video shows how a bomb calorimeter can be set up and operated.

https://youtu.be/ohyA9amFfsc

© Science Media Group

Among the nutrients, the amount of kilocalories per gram that each provide are shown below.

Energy (kcal/g) No Energy

Carbohydrates (4) Vitamins

Proteins (4) Minerals

Lipids (9) Water

As can be seen, only carbohydrates, proteins, and lipids provide energy. However, there is another energy source in the diet that is not a nutrient: alcohol. Just to re-emphasize, alcohol is NOT a nutrient! However, it does provide energy. In fact, alcohol provides seven kilocalories per gram.

Image source: https://img.aws.livestrongcdn.com/ls-article-image-673/ds- photo/getty/article/176/192/517043773.jpg

Phytochemicals, Zoochemicals, and Functional Foods

Beyond macronutrients and micronutrients, there is a lot of interest in non-nutritive compounds found in foods that may be either beneficial or detrimental to health.

Phytochemicals

Phytochemicals are compounds in plants (phyto) that are believed to provide health benefits beyond the traditional nutrients. One example is lycopene in tomatoes, which is thought to potentially decrease the risk of some cancers (in particular prostate cancer). Diets rich in fruits and vegetables have been associated with decreased risk of chronic diseases. Many fruits and vegetables are rich in phytochemicals, leading some to hypothesize that phytochemicals are responsible for the decreased risk of chronic diseases. The role that phytochemicals play in health is still in the early stages of research, relative to other areas of nutrition such as micronutrients. The Linus Paulding Institute has a website containing good information on phytochemicals if you are interested in learning more about them (Interactive web link 1.2).

Image source: https://jbenjaminblog.wordpress.com/tag/tomato/

Interactive web link 1.2

Linus Paulding Institute: Phytochemicals http://lpi.oregonstate.edu/infocenter/phytochemicals.html

Zoochemicals

Zoochemicals are the animal equivalent of phytochemicals in plants. They are compounds in animals that are believed to provide health benefits beyond the traditional nutrients that food contains. Hopefully the name is pretty easy to remember because you can find animals at a zoo. Some compounds can be both phytochemicals and zoochemicals. An example of compounds that can be classified as both are the yellow carotenoids lutein and zeaxanthin. Kale, spinach, and corn contain phytochemicals and are good sources of lutein and zeaxanthin. Whereas egg yolks contain zoochemicals and are also a good source of these carotenoids.

Functional Foods

There are a number of definitions of functional foods. Functional foods are generally understood to be a food, or a food ingredient, that may provide a health benefit beyond the traditional nutrients (macro and micronutrients) it contains. Functional foods are often a rich source of a phytochemical or zoochemical, or contain more of a certain nutrient than a normal food.

Food Quality

One measurement of food quality is the amount of nutrients it contains relative to the amount of energy it provides. High-quality foods are nutrient dense, meaning they contain many of the nutrients relative to the amount of calories they provide. Nutrient-dense foods are the opposite of “empty-calorie” foods such as carbonated sugary soft drinks, which provide many calories

and very little, if any, other nutrients. Food quality is additionally associated with its taste, texture, appearance, microbial content, and how much consumers like it.

Food: A Better Source of Nutrients

It is better to get all your micronutrients from the foods you eat as opposed to from supplements. Supplements contain only what is listed on the label, but foods contain many more macronutrients, micronutrients, and other chemicals, like antioxidants that benefit health. While vitamins, multivitamins, and supplements are a $20 billion industry in this country and more than 50 percent of Americans purchase and use them daily, there is no consistent evidence that they are better than food in promoting health and preventing disease. Dr. Marian Neuhouser, associate of the Fred Hutchinson Cancer Research Center in Seattle, says that “…scientific data are lacking on the long-term health benefits of supplements. To our surprise, we found that multivitamins did not lower the risk of the most common cancers and also had no impact on heart disease.”¹

References & Links

1Woodward, K. “Multivitamins Each Day Will Not Keep Common Cancers Away; Largest Study of Its Kind Provides Definitive Evidence that Multivitamins Will Not Reduce Risk of Cancer or Heart Disease in Postmenopausal Women.” Fred Hutchinson Cancer Research Center. Center News 16 (February 2009). http://www.fhcrc.org/about/pubs/center_news/online/2009/02/multivitamin_study.html

How to Determine the Health Effects of Food and Nutrients

Similar to the method by which a police detective finally charges a criminal with a crime, nutritional scientists discover the health effects of food and its nutrients by first making an observation. Once observations are made, they come up with a hypothesis, test their hypothesis, and then interpret the results. After this, they gather additional evidence from multiple sources and finally come up with a conclusion on whether the food suspect fits the claim. This organized process of inquiry used in forensic science, nutritional science, and every other science is called the scientific method (Figure 1.5).

Image Source: https://s3-us-west-2.amazonaws.com/courses-images/wp- content/uploads/sites/1931/2017/05/30180407/figure-01-01-05.png

Figure 1.5 The basic steps of the scientific method.

In 1811, French chemist Bernard Courtois was isolating saltpeter for producing gunpowder to be used by Napoleon’s army. To carry out this isolation he burned some seaweed and in the process observed an intense violet vapor that crystallized when he exposed it to a cold surface. He sent the violet crystals to an expert on gases, Joseph Gay-Lussac, who identified the crystal as a new element. It was named iodine, the Greek word for violet. The following scientific record is some of what took place in order to conclude that iodine is a nutrient.¹

Image source: http://medicscientist.com/wp-content/uploads/2012/07/GOITERandTHYROIDITIS.jpg

Evidence-Based Approach to Nutrition

It took more than one hundred years from iodine’s discovery as an effective treatment for goiter until public health programs recognized it as such. Although a lengthy process, the scientific method is a productive way to define essential nutrients and determine their ability to promote health and prevent disease. The scientific method is part of the overall evidence- based approach to designing nutritional guidelines.

The Food and Nutrition Board of the Institute of Medicine, a nonprofit, nongovernmental organization, constructs its nutrient recommendations (i.e., Dietary Reference Intakes, or DRI) using an evidence-based approach to nutrition. The same approach is used by the USDA and HHS, which are departments of the US federal government. The USDA and HHS websites are great tools for discovering ways to optimize health; however, it is important to gather nutrition information from multiple resources, as there are often differences in opinion among various scientists and public health organizations. While the new Dietary Guidelines, published in 2010, have been well-received by some, there are nongovernmental public health organizations that are convinced that some pieces of the guidelines may be influenced by lobbying groups and/or the food industry. For example, the Harvard School of Public Health (HSPH) feels the government falls short by being “too lax on refined grains”.²

The guidelines recommend getting at least half of grains from whole grains but according to the HSPH this still leaves too much consumption of refined grains. For a list of reliable sources that advocate good nutrition to promote health and prevent disease using evidence-based science (see Table 1.3 "Web Resources for Nutrition and Health"). In later chapters, we will further discuss distinguishing criteria that will enable you to wade through misleading nutrition information and instead gather your information from reputable, credible websites and organizations. Throughout the course, you are also required to cite credible websites and organizations in your discussion posts.

Table 1.3 Web Resources for Nutrition and Health

Types of Scientific Studies

There are many types of scientific studies that can be used to provide supporting evidence for a particular hypothesis. The various types of studies include epidemiological studies, interventional clinical trials, and randomized clinical interventional trials.

Epidemiological studies are observational studies and are often the front-line studies for public health. The CDC defines epidemiological studies as scientific investigations that define frequency, distribution, and patterns of health events in a population. Thus, these studies describe the occurrence and patterns of health events over time. The goal of an epidemiological study is to find factors associated with an increased risk for a health event, though these sometimes remain elusive. An example of an epidemiological study is the Framingham Heart Study, a project of the National Heart, Lung and Blood Institute and Boston University that has been ongoing since 1948. This study first examined the physical health and lifestyles of 5,209 men and women from the city of Framingham, Massachusetts and has now incorporated data from the children and grandchildren of the original participants. One of the seminal findings of this ambitious study was that higher cholesterol levels in the blood are a risk factor for heart disease.³

Epidemiological studies are a cornerstone for examining and evaluating public health and some of their advantages are that they can lead to the discovery of disease patterns and risk factors for diseases, and they can be used to predict future healthcare needs and provide information for the design of disease prevention strategies for entire populations. Some shortcomings of epidemiological studies are that investigators cannot control environments and lifestyles, a specific group of people studied may not be an accurate depiction of an entire population, and these types of scientific studies cannot directly determine if one variable causes another.

Interventional clinical trial studies are scientific investigations in which a variable is changed between groups of people. When well done, this type of study allows one to determine causal relationships. An example of an interventional clinical trial study is the Dietary Approaches to Stop Hypertension (DASH) trial published in the April 1997 issue of The New England Journal of Medicine. In this study, 459 people were randomly assigned to three different groups; one was put on an average American control diet, a second was put on a diet rich in fruits and vegetables, and the third was put on a combination diet rich in fruits, vegetables, and low-fat dairy products with reduced saturated and total fat intake. The groups remained on the diets for eight weeks. Blood pressures were measured before starting the diets and after eight weeks. Results of the study showed that the group on the combination diet had significantly lower blood pressure at the end of eight weeks than those who consumed the control diet. The

authors concluded that the combination diet is an effective nutritional approach to treat high blood pressure.⁴ The attributes of high-quality clinical interventional trial studies are:

Randomized clinical interventional trial studies are powerful tools to provide supporting evidence for a particular relationship and are considered the “gold standard” of scientific studies. A randomized clinical interventional trial is a study in which participants are assigned by chance to separate groups that compare different treatments. Neither the researchers nor the participants can choose which group a participant is assigned. However, from their limitations it is clear that epidemiological studies complement interventional clinical trial studies and both are necessary to construct strong foundations of scientific evidence for health promotion and disease prevention.

Other scientific studies used to provide supporting evidence for a hypothesis include laboratory studies conducted on animals or cells. An advantage of this type of study is that they typically do not cost as much as human studies and they require less time to conduct. Other advantages are that researchers have more control over the environment and the number of confounding variables can be significantly reduced. Moreover, animal and cell studies provide a way to study relationships at the molecular level and are also helpful in determining the exact mechanism by which a specific nutrient causes a change in health. The disadvantage of these types of studies are that researchers are not working with whole humans and thus the results may not be relevant. Nevertheless, well-conducted animal and cell studies that can be repeated by multiple researchers and obtain the same conclusion are definitely helpful in building the evidence to support a scientific hypothesis.

Evolving Science

Science is always moving forward, albeit sometimes slowly. One study is not enough to make a guideline or a recommendation or cure a disease. Science is a stepwise process that builds on past evidence and finally culminates into a well-accepted conclusion. Unfortunately, not all scientific conclusions are developed in the interest of human health and it is important to know where a scientific study was conducted and who provided the money. Indeed, just as an air

quality study paid for by a tobacco company diminishes its value in the minds of readers, so does one on red meat performed at a laboratory funded by a national beef association. Science can also be contentious even amongst experts that don’t have any conflicting financial interests. Contentious science is actually a good thing as it forces researchers to be of high integrity, well-educated, well-trained, and dedicated (Watch Video 1.4). It also instigates public health policy makers to seek out multiple sources of evidence in order to support a new policy. Agreement involving many experts across multiple scientific disciplines is necessary for recommending dietary changes to improve health and prevent disease. Although a somewhat slow process, it is better for our health to allow the evidence to accumulate before incorporating some change in our diet.

Required Video 1.4

The Experts Debate: This webcast from March 29, 2011 demonstrates how science is always evolving and how debate among nutrition science experts influences policy decisions. https://youtu.be/KBryEJXSaLk

Nutritional Science Evolution

One of the newest areas in the realm of nutritional science is the scientific discipline of nutritional genetics, also called nutrigenomics. Genes are part of DNA and contain the genetic information that make up all our traits. Genes are codes for proteins and when they are turned “on” or “off,” they change how the body works. While we know that health is defined as more than just the absence of disease, there are currently very few accurate genetic markers of good health. Rather, there are many more genetic markers for disease. However, science is evolving and nutritional genetics aims to identify what nutrients to eat to “turn on” healthy genes and “turn off” genes that cause disease. Eventually this field will progress so that a person’s diet can be tailored to their genetics. Thus, your DNA will determine your optimal diet.

Using Science and Technology to Change the Future

As science evolves, so does technology. Both can be used to create a healthy diet, optimize health, and prevent disease. Picture yourself not too far into the future: you are wearing a small “dietary watch” that painlessly samples your blood, and downloads the information to your cell phone, which has an app that evaluates the nutrient profile of your blood and then recommends a snack or dinner menu to assure you maintain adequate nutrient levels. What else is not far off? How about another app that provides a shopping list that adheres to all dietary guidelines and is emailed to the central server at your local grocer who then delivers the food to your home? The food is then stored in your smart fridge which documents your daily diet at home and delivers your weekly dietary assessment to your home computer. At your

computer, you can compare your diet with other diets aimed at weight loss, optimal strength training, reduction in risk for specific diseases or any other health goals you may have. You may also delve into the field of nutritional genetics and download your gene expression profiles to a database that analyzes yours against millions of others.

References & Links

1Zimmerman, M.B. “Research on Iodine Deficiency and Goiter in the 19th and Early 20th Centuries.” J Nutr 138, no. 11 (November 2008): 2060–63. http://jn.nutrition.org/content/138/11/2060.full

2The Harvard School of Public Health. “New US Dietary Guidelines: Progress, Not Perfection.” 2012. The President and Fellows of Harvard College. http://www.hsph.harvard.edu/nutritionsource/whatshould-you-eat/dietary-

guidelines -2010/index.html

3The Framingham Heart Study, a project of the National Heart, Lung, and Blood Institute and Boston University. “History of the Framingham Heart Study.” c 2012 Framingham Heart Study. http://www.framinghamheartstudy.org/about/history.html

4Appel, L. J., et al. “A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure.,” N Engl J Med 336 (April 1997): 1117–24. http://www.nejm.org/doi/full/10.1056/NEJM199704173361601

In addition to nutrition, health is affected by genetics, the environment, life cycle, and lifestyle. These factors are referred to as “determinants” of health and they all interact with each other. For example, family income influences the food choices available and the quantity and quality of food that can be purchased, which of course affects nutrition. Except for nutrition and lifestyle, these factors can be difficult or impossible to change.

Genetics

Everyone starts out in life with the genes handed down to them from the families of their mother and father. Genes are responsible for your many traits as an individual and are defined as the sequences of DNA that code for all the proteins in your body. The expression of different genes can determine the color of your hair, skin, and eyes, and even if you are more likely to be fat or thin and if you have an increased risk for a certain disease. The sequence of DNA that makes up your genes determines your genetic makeup, also called your genome, which is inherited from your mother and father. In 2003, the Human Genome Project was completed and now the entire sequence of DNA in humans is known. It consists of about three billion individual units and contains between twenty-five and thirty thousand genes. The human genome that was sequenced was taken from a small population of donors and is used as a reference DNA sequence for the entire population. Each of us has a similar but unique DNA sequence. Only identical twins and cloned animals have the exact same DNA sequence.

Now that we understand the map of the human genome, let us enter the fields of nutrigenomics and epigenetics. Recall that nutrigenomics is an emerging scientific discipline aimed at defining healthy genes and not-so healthy genes and how nutrients affect them.

Currently, scientists cannot change a person’s DNA sequence. However, they have discovered that chemical reactions in the body can turn genes “on” and “off,” causing changes in the amounts and types of proteins expressed. Epigenetics is another rapidly advancing scientific field in which researchers study how chemical reactions turn genes “on” and “off” and the factors that influence the chemical reactions. Some of these factors are now known to be nutrients. Researchers at the Genetic Science Learning Center at the University of Utah conducted an experiment in which some pregnant mice were fed a diet containing folate, choline, vitamin B12, and betaine, and other pregnant mice were fed a diet that did not contain these nutrients and chemicals. Both groups of pregnant mice were also fed bisphenol A, a chemical in plastic, which alters DNA by inhibiting a specific chemical reaction. The mice born from the mother fed the supplemented diet were brown, thin, and healthy. The mice born from the mother fed the unsupplemented diet were yellow, fat, and unhealthy. This is a dramatic example of how nutrients change not the sequence of DNA, but which genes are expressed.

These two mice look different, but have identical DNA sequences. Thus, not only do the things you eat determine your health but so do the things your mother ate during pregnancy.

Moreover, other studies have demonstrated what your dad ate—and what your grandmother ate while she was pregnant with your mother!—also can affect your gene expression and, consequently, your health. Does this make it OK for you to blame your mother and father for all of your shortcomings? No. Genetics are important in determining your health, but they are certainly not the only determinant.

The Life Cycle

The life cycle of human beings originates from a fertilized egg, which develops into a fetus that is eventually born as a baby. A baby develops into a child, transitions through the wonderful phase of adolescence, becomes an adult, and then advances into old age and eventually death (Figure 1.6 "The Life Cycle: The Forward March to Old Age and Ultimately Death"). The current average life expectancy in America is approaching eighty. To see how this compares with other countries, see Note 1.39 "Interactive 1.3".

© Shutterstock

Figure 1.6 The Life Cycle: The Forward March to Old Age and Ultimately Death.

A person’s stage of life influences their health and nutritional requirements. For example, when you are an adolescent, your bones grow quickly. More calcium, a bone-building nutrient, is required in the diet during this life stage than at other ages. As you get older, the aging process affects how your body functions. One effect of aging, apparently earlier in women than in men, is the deterioration of bone tissue. As a result, women over age fifty-one need more calcium in their diet than younger adult women. Another life-cycle stage, pregnancy, requires several adjustments to nutrition compared to non-pregnant women. It is recommended that a pregnant woman consume more protein than a non-pregnant woman to support growth and

development, and to consume more of some vitamins, such as folate, to prevent certain birth defects. The USDA provides information on healthy diets for many different stages of the life cycle on their website. Healthy aging requires eating a diet that matches one’s life stages to support the body’s specific physiological requirements. What else is known to help a person age slowly and gracefully? Diets high in vegetables and fruits are associated with increased longevity and a decreased risk of many diseases.

Environment

Your environment has a large influence on your health, genetics, life cycle, and lifestyle. Scientists say that the majority of your expressed traits are a product of your genes and environment, of which nutrition is a component. An example of this interaction can be observed in people who have the rare genetic disorder, phenylketonuria (PKU) (Figure 1.7).

Figure 1.7 The interplay of genetics and environment.

Sources: http://topnews.co.uk/214471-rare-disorder-known-phenylketonuria and http://www.georgiapku.org/AboutUs.html. © Shutterstock

The clinical signs of PKU are mental retardation, brain damage, and seizures and are caused by the build-up of the amino acid phenylalanine and its metabolites (breakdown products produced during metabolism) in the body. The high level of phenylalanine in a person who has PKU is the result of a change in the gene that encodes for an enzyme that converts phenylalanine into the amino acid tyrosine. This genetic change, called a mutation, causes the enzyme to not function properly. In this country and many others, all newborn babies are screened for PKU in order to diagnose and treat the disease before the development of mental retardation and brain damage. Once diagnosed, PKU is treated by strict adherence to a diet low

in phenylalanine, consisting mostly of fruits, vegetables, and grains. Adhering to this diet for life allows an individual with PKU to lead a normal life without suffering the consequences of brain damage, mental retardation, or seizures. In the example of PKU, the consequences of a genetic mutation are modified by diet. Thus, a person’s genes can make them more susceptible to a particular disease, or cause a disease, and their environment can decrease or increase the progression and severity of the condition.

Socioeconomic Status

Multiple aspects of a person’s environment can affect nutrition, which in turn affects health. One of the best environmental predictors of a population’s health is socioeconomic status. Socioeconomic status is a measurement made up of three variables: income, occupation, and education. Socioeconomic status affects nutrition by influencing what foods you can afford and consequently, food choice and food quality. Nutrition and health are generally better in populations that have higher incomes, better jobs, and more education. On the other hand, the burden of disease is highest in the most disadvantaged populations. A commentary in the Journal of the American Medical Association reports that the lower life expectancy of populations of lower socioeconomic status is largely attributable to increased death from heart disease. The American Heart Association states that having a healthy diet is one of the best weapons to fight heart disease and it is therefore essential that all socioeconomic status groups have access to high-quality, nutrient-dense foods. The disparities in nutrition and health in America are directly related to the disparity in socioeconomic status.¹

Other dimensions that affect health disparity are race, ethnic group, sex, sexual identity, age, disability, and geographic location. The federal government recognizes the issue of inequitable health among Americans and one of the overarching goals of Healthy People 2020, a large program managed by the HHS, is to “Achieve health equity, eliminate disparities, and improve the health of all groups.” To work toward this monumental goal, the HHS is actively tracking disease patterns, chronic conditions, and death rates among the many different types of people that live in the United States.

Lifestyle

One facet of lifestyle is your dietary habits. Recall that we discussed briefly how nutrition affects health. A greater discussion of this will follow in subsequent chapters of this book as there is an enormous amount of information regarding this aspect of lifestyle. Dietary habits include what a person eats, how much a person eats during a meal, how frequently meals are consumed, and how often a person eats out at restaurants. Other aspects of lifestyle include physical activity level, recreational drug use, and sleeping patterns, all of which play a role in health and impact nutrition. Following a healthy lifestyle improves your overall health.

Physical Activity Level

In 2008, the HHS released the Physical Activity Guidelines for Americans (Interactive web link 1.3). The HHS states, “Being physically active is one of the most important steps that Americans of all ages can take to improve their health. The 2008 Physical Activity Guidelines for Americans provides science-based guidance to help Americans aged six and older improve their health through appropriate physical activity.” The guidelines recommend exercise programs for people in many different stages of their lifecycle including for pregnant women and for adults and children who have disabilities. The HHS reports that there is strong evidence that increased physical activity decreases the risk of early death, heart disease, stroke, Type 2 diabetes, high blood pressure, and certain cancers; prevents weight gain and falls; and improves cognitive function in the elderly. New guidelines are expected to be released in 2018.

Interactive web links 1.3:

2008 Physical Activity Guidelines for Americans

https://health.gov/PAGuidelines/default.aspx

Recreational Drug Use

Recreational drug use, which includes tobacco smoking and alcohol consumption along with narcotic and other illegal drug use, has a large impact on health. Smoking cigarettes causes lung cancer, eleven other types of cancer, heart disease, and several other disorders or diseases that markedly decrease quality of life and increase mortality. In the United States, smoking causes more than four hundred thousand deaths every single year, which is far more than deaths associated with any other lifestyle component.² Also according to the CDC, excessive alcohol intake causes an estimated seventy-five thousand deaths per year.³

Staying away from excessive alcohol intake lowers blood pressure, the risk from injury, heart disease, stroke, liver problems, and some types of cancer. Abstaining from alcohol also aids in weight loss and increases the money in your wallet. While heavy drinking of alcoholic beverages is associated with several bad health effects, consuming alcohol in moderation has been found to promote health such as reducing the risk for heart disease and Type 2 diabetes in some people. The HHS defines drinking in moderation as no more than one drink a day for women and two drinks a day for men. Illicit and prescription drug abuse are associated with decreased health and is a prominent problem in the United States. The health effects of drug abuse can be far-reaching including increased risk for stroke, heart disease, cancer, lung disease, and liver disease.

Sleeping Patterns

Inadequate amounts of sleep, or not sleeping well, can also have remarkable effects on a person’s health. In fact, sleeping can affect your health just as much as diet or exercise. At least 10 percent of Americans have chronic insomnia. Scientific studies have shown that insufficient sleep increases the risk for heart disease, Type 2 diabetes, obesity, and depression. Abnormal breathing during sleep, a condition called sleep apnea, is also linked to an increased risk for chronic disease.⁴ (Watch Video 1.5)

Required Video 1.5

Brief promotional video with easy to follow tips to improve your sleep and hence overall well- being. https://youtu.be/DMX1P8fDrlc

Nutrition, Genetics, Environment, and Lifestyle Interact to Affect Health

The Pima Indians who inhabit parts of southern Arizona and the Pima Indians that live across the border in Mexico are genetically and culturally similar, but there are vast differences in the health of these two populations. In America, the Pima Indians have the highest rate of obesity and Type 2 diabetes compared to any other ethnic group. However, the Pima Indians who live in Mexico do not share these same health problems because of a complex interplay between nutrition, genetics, environment, and lifestyle. Over one hundred years ago, the Pima Indians were farmers, hunters, and gatherers and their diets consisted of about 70 percent carbohydrate, 15 percent protein, and 10 to 15 percent fat. Typical of the lives of farmers, hunters, and gatherers a century ago, they lived through times of feast and times of famine.

The geneticist James Neel proposed in 1962 that the Pima Indians carried a “thrifty gene” that makes them very efficient at storing fat during times of plenty so they do not starve when food is scarce. After World War II, the Pima Indians in America either went back to reservations in southern Arizona or moved to the cities for work. They rapidly adopted the American diet and lifestyle and consumed high-fat, processed foods, and refined grains and were more sedentary than their counterparts in Mexico, who retained their more traditional diet and lifestyle. Today, the typical American Pima Indian diet obtains more than 40 percent of calories from fat. The “thrifty gene” in the American Pima Indian population increased their susceptibility to the consequences of the high-fat American diet and sedentary lifestyle because they were genetically better at storing fat than others. The story of the Pima Indians and the difference between the health of their populations in America and Mexico demonstrates the interactions between nutrition, genetics, environment, and lifestyle. Indeed, preliminary studies suggest that when American Pima Indians switch back to the diets of their ancestors and consume

beans, corn, grains, and greens and other low-fat, high-fiber plant foods, the benefits are weight loss and reduced risk of chronic disease. The health status of American Pima Indians is considered “a canary in the coal mine,” meaning they provide a warning to the American people (Figure 1.8).

Although the health consequences of the American diet and lifestyle in Pima Indians appeared rapidly in their population, all Americans that partake in the current trends of American diet and lifestyle are at risk. On the lighter side (literally!), the new studies that show changing back to more traditional diets markedly improved the health of the American Pima Indians suggest that all Americans can reduce their risk for diet-related diseases even when their genetic susceptibility for these diseases is high.

Pima Indians living in America are genetically similar to those who live in Mexico, but differences in their nutrition, environment, and lifestyle changes their health.

Source: http://paleobioticslab.com/general-interest-articles/so-go-the-pimas-so-go-the-rest-of-us/.

Figure 1.8 The Interplay of Nutrition, Genetics, Environment, and Lifestyle Affects Health.

Personal Choice: The Challenge of Choosing Foods

From visiting websites about traditional foods of different cultures and ethnic groups, you may have noticed that a few more things besides environment and lifestyle that influence the foods you choose to eat. Different foods affect energy level, mood, how much is eaten, how long before you eat again, and if cravings are satisfied. We have talked about some of the physical effects of food on your body, but there are other effects too. Food regulates your appetite and

how you feel. Multiple studies have demonstrated that some high-fiber foods and high-protein foods decrease appetite by slowing the digestive process and prolonging the feeling of being full. The effects of individual foods and nutrients on mood are not backed by consistent scientific evidence but in general, most studies support that healthier diets are associated with a decrease in depression and improved well-being. To date, science has not been able to track the exact path in the brain that occurs in response to eating a particular food, but it is quite clear that foods, in general, stimulate emotional responses in people.

Food also has psychological, cultural, and religious significance, so your personal choices of food affect your body, mind, and soul. The social implications of food have a great deal to do with what people eat, as well as how and when. Special events in individual lives—from birthdays to funerals—are commemorated with equally special foods. Being aware of these forces can help people make healthier food choices—and still honor the traditions and ties they hold dear. Typically, eating kosher food means a person is Jewish; eating fish on Fridays during Lent means a person is Catholic; fasting during the ninth month of the Islamic calendar means a person is Muslim. On New Year’s Day, people from New England like to combine pork and sauerkraut as a way to eat their way to luck. Several hundred miles away in the southern United States, people eat Hoppin’ John, a favorite local dish made with black-eyed peas and pork, while fish is the “lucky” food of choice for Japanese Americans. National food traditions are carried to other countries when people immigrate. American cuisine would not be what it is today without the contributions of Italian, Chinese, Mexican, and other immigrants.

Factors that Drive Food Choices

Along with these influences, a number of other factors affect the dietary choices individuals make, including:

convenient, but might not offer substantial nutrition. Yet getting in the habit of drinking an ample amount of water each day can yield multiple benefits.

References & Links

1Fiscella, K. and D. Tancredi. “Socioeconomic Status and Coronary Heart Disease Risk Prediction.” JAMA 300, no. 22 (2008): 2666–68.

2Centers for Disease Control and Prevention. “Smoking and Tobacco Use.” Last updated March 21, 2011. http://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/tobacco_related_mortality/index.htm 3Centers for Disease Control and Prevention. “Alcohol and Drug Use.” Last updated June 7, 2012. http://www.cdc.gov/healthyyouth/alcoholdrug/

4National Sleep Foundation. “Can’t Sleep? What to Know about Insomnia.” Accessed February 12, 2012. http://www.sleepfoundation.org/article/sleep-related-problems/insomniaand-sleep

You may remember that when you were younger your mother or grandmother made you swallow that teaspoonful of cod liver oil because she said it was good for you. You don’t have to have a PhD to know some of the basic ways you can adapt your life to be healthier. However, the mainstream media inundates the American population with health cures and tips, making it confusing to develop the best plan for your health. This section will equip you with tools to assess and improve your health.

Personal Health Assessment

One of the easiest places to begin a personal health assessment is by examining the results from your last physical. Often a person will leave the doctor’s office without these results. Remember that the results belong to you and having this information on hand provides you with much of what you need to keep track of your health. During a physical, after obtaining weight and height measurements, a nurse will typically examine blood pressure. Blood pressure is a measurement of the forces in the arteries that occur during each heartbeat. It is a principle vital sign and an indicator of cardiovascular health.

In most circumstances, a physical includes blood tests, which measure many health indicators, and you have to request the results. Once you have the results-in-hand, it is good practice to file them in a binder so you can compare them from year to year. This way you can track your blood-cholesterol levels and other blood-lipid levels and blood-glucose levels. These are some of the more general measurements taken but in many instances, blood tests also examine liver and kidney function, vitamin and mineral levels, hormone levels, and disease markers. Your doctor uses all of these numbers to assess your health and you can use them to play a more active role in keeping track of your health.

Hearing and vision are additionally part of a general health assessment. If you wear glasses, contacts, or a hearing aid you already are aware of how important it is to know the results of these exams. If you have not experienced vision or hearing problems yet your likelihood of experiencing them markedly increases over the age of forty. Another component of overall health is oral health. The health of your teeth, gums, and everything else in your mouth are an integral component of your overall health. This becomes apparent when a person experiences a tooth infection, which if left untreated significantly impairs physical, mental, and social well- being.

Other indicators of health that you can measure yourself are body mass index (BMI) and fitness. BMI is a standardized measurement that indicates if a person is underweight, of normal weight,

overweight, or obese and is based on data from the average population. You can calculate this yourself or use one of the many BMI calculators on the web (Interactive web links 1.4). It has some limitations. One limitation is that it does not take into account how much of your weight is made up of muscle mass, which weighs more than fat tissue. BMI and other measurements of body composition and fitness are more fully discussed in later chapters. This discussion of a personal health assessment has focused primarily on physical health, but remember that mental and social well-being also affect health. During a physical, a doctor will ask how you are feeling, if you are depressed, and if you are experiencing behavioral problems. Be prepared to answer these questions truthfully, so that your doctor can develop a proper treatment plan to manage these aspects of health.

Interactive web links 1.4:

BMI Calculator for Adults: https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/english_bmi_calculator/bmi_calcula tor.html

BMI Calculator for Teens and Children: https://nccd.cdc.gov/dnpabmi/calculator.aspx

Taking charge of your health will pay off and equip you with the knowledge to better take advantage of your doctor’s advice during your next physical. Health calculators, such as those that calculate BMI, ideal weight, target heart rate among many others, and personal health assessments will help you to take charge of your health, but they should not take the place of visiting your doctor.

Dietary Assessment

The first step in assessing your diet is to find out if the foods you eat are good for your health and provide you with all the nutrients you need. Begin by recording in a journal what you eat every day, including snacks and beverages. You can track calories over time, diet quality, and find many other tools to evaluate your daily food consumption at www.choosemyplate.org. The questions these tools can help answer include: How much food do you have to eat to match your level of activity? How many calories should you eat? What are the best types of food to get the most nutrients? What nutrients are contained in different foods? How do you plan a menu that contains all the nutrients you need? Make the first step and assess your diet. This book will provide you with interactive resources, videos, and audio files to empower you to create a diet that improves your health.

Family Medical History

Because genetics play a large role in defining your health, it is a good idea to take the time to learn some of the diseases and conditions that may affect you. To do this, you need to record your family’s medical history. Start by simply drawing a chart that details your immediate family and relatives. Many families have this and you may have a good start already. The next time you attend a family event start filling in the blanks. What did people die from? What country did Grandpa come from? While this may be a more interesting project historically, it can also provide you with a practical tool to determine what diseases you might be more susceptible.

This will allow you to make better dietary and lifestyle changes early on to help prevent a disease from being handed down from your family to you. It is good to compile your information from multiple relatives.

Lifestyle Assessment

A lifestyle assessment includes evaluating your personal habits, level of fitness, emotional health, sleep patterns, and work-life balance. Many diseases are preventable by simply staying away from certain lifestyles. Don’t smoke, don’t drink excessively, and don’t do recreational drugs. Instead, make sure you exercise. Find out how much to exercise by reading the 2008 Physical Activity Guidelines for Americans. There is a wealth of scientific evidence that increased physical activity promotes health, prevents disease, and is a mood enhancer. Emotional health is often hard to talk about; however, a person’s quality of life is highly affected by emotional stability. Harvard’s Women’s Health Watch notes six reasons to get enough sleep: Sleep promotes healthy brain function, while lack of sleep can cause weight gain and increase appetite, decrease safety (falling asleep while driving), make a person moody and irritable, decrease health of the cardiovascular system and prevent the immune system from functioning well.¹

Finding balance between work and life is a difficult and continuous process involving keeping track of your time, taking advantage of job flexibility options, saying no, and finding support when you need it. Work-life balance can influence what you eat too.

References & Links

1Harvard Health Publications. “Importance of Sleep: Six Reasons Not to Scrimp on Sleep.” Harvard’s Women’s Health Watch (January 2006). c 2000–2012 Harvard University.

http://www.health.harvard.edu/press_releases/importance_of_sleep_and _health

The science of nutrition includes the study of how organisms obtain food from their environment. An ecosystem is defined as the biological and physical environments and their interactions with the community of organisms that inhabit those environments as well as the interactions among the organisms. Human nutrition and the health of the world’s ecosystem are interdependent, meaning that what we eat and where we get it from affects the world. In turn, the health of the earth influences our health. The term sustainability is used to indicate the variety of approaches aimed at improving our way of life. Sustainability promotes the development of conditions under which people and nature can interact harmoniously. It is based upon the principle that everything needed for human survival depends upon the natural environment.

A major theme of sustainability is to ensure that the resources needed for human and environmental health will continue to exist. A healthy ecosystem, one that is maintained over time, is harmonious and allows for social and economic fulfillment for present and future generations. Nutritious foods come from our ecosystem and to ensure its availability for generations to come, it must be produced and distributed in a sustainable way. The American Public Health Association (APHA) defines a sustainable food system as “one that provides healthy food to meet current food needs while maintaining healthy ecosystems that can also provide food for generations to come with minimal negative impact to the environment.”¹

It also states the attributes of a sustainable food system are:

Available Accessible Affordable to all Humane

jJst

A sustainable food system does not just include the food and those who consume the food, but also those that produce the food, like farmers and fishermen, and those who process, package, distribute, and regulate food. Unfortunately, we have a long way to go to build a sustainable food system.

The Challenges

The most prominent challenge to building a sustainable food system is to make food available and accessible to all. The Food and Agricultural Organization of the United Nations (FAO) states the right to food is a fundamental human right and its mission is to assist in building a food- secure world. Food security in America (Figure 1.9) is defined as the “access by all people at all times to enough food for an active, healthy life.”²

Image Source: Calculated by ERS using data from the December 2009 Current Population Survey Food Security Supplement.

Figure 1.9 Food Security Status in the United States.

As of 2009, 14.9 percent of households, or 17.4 million people in the United States, had very low or low food security and these numbers have risen in recent years.³

Food security is defined by the FAO as existing “when all people, at all times, have physical, social, and economic access to sufficient, safe, and nutritious food which meets their dietary needs and food preferences for an active and healthy life.” (Figure 1.10) The FAO estimates that 925 million worldwide were undernourished in 2010. Although there was a recent decline in overall food insecurity (attributable mostly to a decline in undernourished people in Asia), the number of undernourished people world-wide is still higher than it was in 1970, despite many national and international goals to reduce it.⁴

Source: Calculated by ERS based on Current Population Survey Food Security Supplement data.

Figure 1.10 Food Insecurity: A Global Perspective.

Another challenge to building a sustainable food system is to supply high-quality nutritious food. The typical American diet does not adhere to dietary guidelines and recommendations, is unhealthy, and thus costs this country billions of dollars in healthcare. The average American diet contains too many processed foods with added sugars and saturated fats and not enough fruits, vegetables, and whole grains. Moreover, the average American takes in more kilocalories each day than ever before. This shift of the population toward unhealthy, high-calorie diets has fueled the obesity and diet-related disease crisis in this nation. Overall the cost of food for the average American household has declined since the 1970s; however, there has been a growth of “food deserts.” A food desert is a location that does not provide access to affordable, high- quality, nutritious food. One of the best examples of a “food desert” is in Detroit, Michigan. The lower socioeconomic status of the people who live in this city does not foster the building of grocery stores in the community. Therefore, the most accessible foods are the cheap, high- caloric ones sold in convenience stores. As a result, people who live in Detroit have some of the highest incidences of obesity, Type 2 diabetes, and cardiovascular disease in the country.

A fourth challenge to building a sustainable food system is to change how we produce, process, and distribute food. Large agribusiness, complex industrial processing, and massive retail conglomerations distort the connection we have between the food on our plate and where it came from. More food is being produced in this nation than ever before, which might sound

good at first. However, some factors that have contributed to higher food production include using genetically engineered plants, excessive use of herbicides and pesticides, and the selective promotion of only a few crops by the policy of crop-specific subsidies (money given to farmers by the federal government). The subsidies are given toward the support of only about eight crops, most notably corn and soybeans. This policy diminishes the variety of crops, decreases biodiversity among crops, and supports large agribusiness while disadvantaging small- and medium-sized farms. Additionally, the whole system of food production, processing, and distribution is lengthy, requiring a great deal of energy and fossil fuels, and promotes excessive use of chemicals to preserve foods during transportation and distribution. In fact, the current US food system uses approximately 22 percent of the energy in this country and is responsible for at least 20 percent of greenhouse gas emissions.⁵

Solutions to the Challenges

While these challenges are daunting there are many potential solutions that are gaining momentum in the United States. The APHA advocates expanding the infrastructure for locally grown food, improving access to healthy and local food for low-income Americans, providing education on food origin and production, building up the livelihoods of local farmers, and using sustainable farming methods. Detroit is currently a “food desert,” but there is a fantastic example of how to positively impact the growth of a sustainable food system within the city. It is called the Eastern Market and it is a six-block inner city market with over 250 vendors marketing local produce, meat, seafood, plants, fresh-cut flowers and much, much more. Unlike many urban farmers’ markets it sells foods that are of better quality and lower prices than grocery stores. Its forty-thousand visitors every Saturday demonstrate its success as a community-based way to foster good nutrition, good health, and social interaction.

References & Links

1American Public Health Association. “Towards a Healthy, Sustainable Food System.” Policy Statement Database. Policy no. 200712 (November 6, 2007). http://www.apha.org/advocacy/policy/policysearch/default.htm?id=1361 2US Department of Agriculture, Economic Research Service. “Food Security in the United States: Key Statistics and Graphics.” Last updated June 4, 2012. http://www.ers.usda.gov/Briefing/FoodSecurity/stats_graphs.htm#food_secure

3Food and Agricultural Organization of the United Nations. “Food Security: Concepts and Measurement.” In

Corporate Document Repository, ID: 144369. 2003. http://www.fao.org/docrep/005/y4671e/y4671e06.htm

4Food and Agriculture Organization of the United Nations. “How Does International Price Volatility Affect Domestic Economies and Food Security? In The State of Food Insecurity in the World. 2011. http://www.fao.org/publications/sofi/en/

5Canning, P. et al. “Energy Use in the US Food System.” US Department of Agriculture, Economic Research Report, no. ERR-94 (March 2010). http://www.ers.usda.gov/Publications/ERR94/ERR94_ReportSummary.pdf

Chapter 2: Energy-Yielding Macronutrients

As you have learned, there are three energy-yielding macronutrients: carbohydrates, proteins, and lipids. The energy contained in these molecules is found in the electrons that are shared in the covalent bonds that link the atoms. Our individual cells (in a process called Cellular Respiration, documented in a later chapter) deconstruct these molecules, and use the energized electrons to generate the ATP needed to keep our cells alive. This chapter goes more in depth about these major dietary components that are so critical to life.

Sections:

Carbohydrates

Carbohydrates have become surprisingly divisive. Some people swear by them, others swear against them. But it is important to understand that carbohydrates are a diverse group of compounds that have a multitude of effects in the body. Thus, trying to make blanket statements about carbohydrates is probably not a good idea.

Carbohydrates are named because they are hydrated (as in water, H₂O) carbon. Below is the formula showing how carbon dioxide (CO₂) and water (H₂O) are used to make carbohydrates (CH₂O)_n and oxygen (O₂). The “n” after the carbohydrate in the formula indicates that the chemical formula is repeated an unknown number of times, but that for every carbon and oxygen, there will always be two hydrogens. Putting it another way: a carbohydrate always contains carbon, hydrogen, and oxygen atoms in a ratio of 1:2:1.

CO₂ + H₂O --> (CH₂O)_n + O₂

Carbohydrates are produced by plants through a process known as photosynthesis. In this process, plants use the energy from photons of light to synthesize carbohydrates. The formula for this reaction looks like this:

Carbon Dioxide + water  Carbohydrate (Glucose) and Oxygen

6CO₂ + 6H₂O + Light --> C₆H₁₂O₆ + 6O₂

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Light (sunlight) in the reaction above is the energy that will ultimately be stored in the glucose molecule (C₆H₁₂O₆). This will be the energy available for use when a human being consumes a glucose molecule! There are many different types of carbohydrates as shown in the figure below. One way that carbohydrates can be classified is into simple carbohydrates, complex carbohydrates, and sugar alcohols. As the names imply, complex carbohydrates contain more sugar units, while simple carbohydrates contain either 1 or 2 sugars. In the next sections, you will learn more about the different forms of carbohydrates.

Figure 2.11 The different forms of carbohydrates Subsections:

No References

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Simple Carbohydrates

As shown in the figure below, simple carbohydrates can be further divided into monosaccharides and disaccharides. Mono- means one, thus monosaccharides contain one sugar. Di- means two, thus disaccharides contain 2 sugar units.

Figure 2.111 Overview of Carbohydrates

Monosaccharides

While there are many organic compounds that qualify as monosaccharides, there are only three that are found in the foods we eat. These three monosaccharides are: glucose, fructose and galactose. Notice that all are 6-carbon sugars (hexoses). However, fructose has a five member ring, while glucose and galactose have 6 member rings. Also notice that the only structural difference between glucose and galactose is the position of the alcohol (OH) group that is shown in red.

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Figure 2.112 The 3 monosaccharides

Despite these differences in structure, glucose, galactose, and fructose have the same chemical formula (C₆H₁₂O₆). Molecules with a common chemical formula, yet different chemical structures, are called isomers. These three monosaccharides are additionally characterized by the following:

Glucose - Product of photosynthesis, major source of energy in our bodies Fructose - Commonly found in fruits and used commercially in many beverages

Galactose - Not normally found in nature alone, normally found in the disaccharide lactose (also known as milk sugar)

Required Web Link

Not familiar with ring structures? See how glucose forms a ring.

Disaccharides

Disaccharides are produced from 2 monosaccharides. The commonly occurring disaccharides are:

Maltose (glucose + glucose, aka malt sugar) - seldom found in foods, present in alcoholic beverages and barley

Sucrose (glucose + fructose, aka table sugar) - only made by plants.

Lactose (galactose + glucose, aka milk sugar) - primary milk sugar

The different disaccharides and the monosaccharides components are illustrated in Figure 2.113.

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Figure 2.113 The 3 disaccharides

Each of these disaccharides contains glucose and all the reactions are dehydration reactions (a reaction that creates a link between two molecules through the loss of a molecule of water).

You might hear the term glycosidic bond used to identify the bonds between monosaccharides. A glycoside is a sugar, so glycosidic is referring to a sugar bond. Interestingly, lactose has a unique glycosidic bond. People require special enzyme, lactase, to break this bond, and the absence of lactase activity leads to lactose intolerance.

High-Fructose Corn Syrup

Food manufacturers are always searching for cheaper ways to produce their food. One method that has been popular is the use of high-fructose corn syrup as an alternative to sucrose. High- fructose corn syrup contains either 42 or 55% fructose, which is similar to sucrose1.

Nevertheless, because an increase in high-fructose corn syrup consumption (see figure below) has coincided with the increase in obesity in the U.S., there is a lot of controversy surrounding its use.

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Figure 2.114 U.S. per capita sugar and sweetener consumption2

Opponents claim that high-fructose corn syrup is contributing to the rise in obesity rates. As a result, some manufactures have started releasing products made with natural sugar. You can read about this trend in the following New York Times article in the link below. Also, manufacturers tried to rebrand high-fructose corn syrup as corn sugar to get around the negative perception of the name. But the FDA rejected the Corn Refiners Association request to change the name officially to corn sugar as described in the second link. The last link is a video made by the American Chemical Society that gives some background on how HFCS is produced and how it compares to sucrose.

Required Web Links

Sugar is back on labels, this time as a selling point No new name for high-fructose corn syrup

(Video): Sugar vs. High Fructose Corn Syrup - What's the Difference? (2:41)

References & Links

Links

Not familiar with Ring structures? See how glucose forms a ring - http://en.wikipedia.org/wiki/File:Glucose_Fisher_to_Haworth.gif

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Sugar is back on labels, this time as a selling point - http://www.nytimes.com/2009/03/21/dining/21sugar.html?_r=1&ref=nutrition

No new name for high-fructose corn syrup - http://well.blogs.nytimes.com/2012/05/31/no-new-name-for-high- fructose-corn-syrup/?_r=0

Video

Sugar vs. High Fructose Corn Syrup – What's the Difference? - https://www.youtube.com/watch?v=fXMvregmU1g

Sugar Alcohols (Polyols, Sugar Replacers)

Sugar(s) can provide a lot of calories and contribute to tooth decay. Thus there are many other compounds that are used as alternatives to sugar that have been developed or discovered. We will first consider sugar alcohols and then the alternative sweeteners in subsequent sections.

Below you can see the structure of three common sugar alcohols: xylitol, sorbitol, and

mannitol.

Figure 2.121 Structure of three commonly used sugar alcohols: xylitol, sorbitol, and mannitol1-3 Remember that alcohol subgroups are (OH), and you can see many of them in these structures.

Sugar alcohols are also known as "sugar replacers", because some in the public might get confused by the name sugar alcohol. Some might think a sugar alcohol is a sweet alcoholic beverage. Another name for them is nutritive sweeteners, which indicates that they do provide calories. Sugar alcohols are nearly as sweet as sucrose but only provide approximately half the calories as shown below. The name polyols also seems to be increasingly used to describe these compounds.

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Table 2.121 Relative sweetness of monosaccharides, disaccharides, and sugar alcohols4,5

*Differs based on a person’s lactase activity

Sugars are fermented by bacteria on the surfaces of teeth. This results in a decreased pH (higher acidity) that leads to tooth decay and, potentially, cavity formation (a process officially known as dental caries). The major advantage of sugar alcohols over sugars is that sugar alcohols are not fermented by bacteria on the tooth surface. There is a nice picture of this process in the link below as well as a video explaining the process of tooth decay.

Required Web Links Sugar and Dental Caries Video: Tooth Decay (1:06)

References & Links

Link

Sugar and Dental Caries - http://www.asu.edu/courses/css335/caries.htm

Video

Tooth Decay - http://www.youtube.com/watch?v=_oIlv59bTL4

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Alternative Sweeteners

Alternative sweeteners are simply alternatives to sucrose and other mono- and disaccharides that provide sweetness. Many have been developed to provide zero-calorie or low calorie sweetening for foods and drinks.

Because many of these provide little to no calories, these sweeteners are also referred to as non-nutritive sweeteners (FDA is using high-intensity sweeteners to describe these products3). Aspartame does provide calories, but because it is far sweeter than sugar, the small amount used does not contribute meaningful calories to a person's diet. Until the FDA allowed the use of the term stevia, this collection of sweeteners was commonly referred to as artificial sweeteners, because they were synthetically or artificially produced. However, with stevia, the descriptor artificial can no longer be used to describe these sweeteners. More recently, Luo Han Guo (monk fruit) extracts have also been allowed to be used as another high-intensity sweetener that is not synthesized or artificially produced. The table in the link below summarizes the characteristics of the FDA approved high-intensity sweeteners.

Required Web Link

FDA High-Intensity Sweeteners

Saccharin

Saccharin is the oldest of the artificial sweeteners. Saccharin was linked to bladder cancer in rats in the late 70’s, but subsequent research did not establish the link in humans. While saccharin might not present as a significant health hazard, you do not want to use it in cooking or baking because it develops a bitter taste4.

Figure 2.131 Structure of saccharin5

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Cyclamate

Cyclamate (sodium cyclamate) is a artificial sweetener that was discovered in 1937. It was banned by the FDA in 1969, primarily due to its questionable safety. Cyclamate is about 30 times sweeter than sucrose, and is often used in combination with other artificial sweeteners. Cyclamate is approved for use in over 80 countries, including those in the European Union and Canada.

Aspartame

Aspartame is made up of 2 amino acids (phenylalanine and aspartate) and a methyl (CH₃) group. Aspartame is marketed under the product name NutraSweet ®. The compound is broken down during digestion into the individual amino acids. This is why it provides 4 kcal/g, just like protein4. Because it can be broken down to phenylalanine, products that contain aspartame contain the following message: "Phenylketonurics: Contains phenylalanine." Phenylketonuria (PKU) will be covered in greater detail in section 2.25. When heated, aspartame breaks down and loses its sweet flavor1.

Figure 2.132 Structure of aspartame6

Neotame

Neotame is like aspartame version 2.0. Neotame is structurally identical to aspartame except that it contains an additional side group (bottom of figure below, which is flipped backwards to make it easier to compare their structures). While this looks like a minor difference, it has profound effects on the properties of neotame. Neotame is much sweeter than aspartame and is heat-stable. It can still be broken down to phenylalanine, but such small amounts are used that it is not a concern for those with PKU1,4.

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Figure 2.133 Structure of neotame7

Advantame

The newest, sweetest alternative sweetener approved by the FDA in 2014 is advantame. It is heat-stable and does not have a trade name yet3. Notice it also has a similar structure to aspartame and neotame. Like Neotame, it can be broken down to phenylalanine, but such small amounts are used that it is not a concern for those with PKU. However, it has a much higher acceptable daily intake than Neotame4, meaning there is less concern about adverse effects from consuming too much.

Figure 2.134 Structure of advantame8

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Acesulfame-Potassium (K)

Acesulfame-potassium (K) is not digested or absorbed, therefore it provides no energy or potassium to the body1. It is a heat-stable alternative sweetener.

Figure 2.135 Structure of acesulfame-potassium (K)9

Sucralose

Sucralose is structurally identical to sucrose except that 3 of the alcohol groups (OH) are replaced by chlorine molecules (Cl). This small change causes sucralose to not be digested and as such is excreted in feces1,4. It is a heat-stable alternative sweetener.

Figure 2.136 Structure of sucralose10

Stevia

Stevia is a heat-stable alternative sweetener derived from a South American shrub, with the leaves being the sweet part. The components responsible for this sweet taste are a group of compounds known as steviol glycosides. The structure of steviol is shown in Figure 2.137.

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Figure 2.137 Structure of steviol12

The term glycoside means that there are sugar molecules bonded to steviol. The two predominant steviol glycosides are stevioside and rebaudioside A. The structure of these two steviol glycosides are very similar13. The structure of stevioside is shown below as an example.

Figure 2.138 Structure of stevioside14

The common name for a sweetener containing primarily rebaudioside A is rebiana13. Stevia sweeteners have been marketed as natural alternative sweeteners, something that has been stopped by lawsuits as described in the following link.

Required Web Link

What is natural and who decides?

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Luo Han Guo Extracts

Luo Han Guo (aka Siraitia grosvenrii Swingle, monk fruit) extracts are a newer, natural heat- stable alternative sweetener option derived from a native Chinese fruit. These extracts are sweet because of the mogrosides that they contain3. The structure of a mogroside is shown below.

Figure 2.139 Structure of a mogroside15

References & Links

Links

FDA High-Intensity sweeteners - http://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm397725.htm

What is natural and who decides? - http://www.nutraingredients-usa.com/Markets/Pure-Via-to-settle-class- action-suit-over-natural-claims

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Oligosaccharides

Within the category of complex carbohydrates, there are oligosaccharides and polysaccharides. Oligosaccharides (oligo means few) are composed of 3-10 sugar units and polysaccharides contain greater than 10 sugar units.

Figure 2.141 Overview of carbohydrates

Raffinose and stachyose are the most common oligosaccharides. They are found in legumes, onions, broccoli, cabbage, and whole wheat1. The link below shows the raffinose and stachyose content of some plant foods.

Required Web Link

Raffinose and stachyose content of selected plant foods

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The structures of the two oligosaccharides are shown below.

Figure 2.142 Structure of raffinose2

Figure 2.143 Structure of stachyose3

Our digestive system lacks the enzymes necessary to digest the unique glycosidic bonds found in oligosaccharides. As a result, the oligosaccharides are not digested in the small intestine and reach the colon where they are fermented by the bacteria there. Gas (methane, CH₄) is produced as a byproduct of this bacteria fermentation that can lead to flatulence. To combat this problem, Beano® is a popular product that contains an enzyme (alpha-galactosidase) to break down oligosaccharides, thereby preventing them from being used to produce gas. The video link below describes how Beano® works.

Required Web Link

(Video) Beano's University of Gas: Lesson 2

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References & Links

Videos

Raffinose and stachyose content of foods - http://books.google.com/books?id=LTGFV2NOySYC&pg=PA374&lpg=PA374&dq=raffinose+and+stachyose+conten t+of+vegetables&source=bl&ots=X4Dr7jWmwL&sig=CJFvhAIysSZCP2SOy_MqhfoVYQQ&hl=en&ei=TSRITdTfLNH0gA fB2MX_BQ&sa=X&oi=book_result&ct=result&resnum=6&ved=0CD0Q6AEwBQ#v=onepage&q=raffinose%20and%2 0stachyose%20content%20of%20vegetables&f=false

Beano's University of Gas - http://beano.com.cn/university-of-gas#

Polysaccharides

Poly means "many" and thus polysaccharides are made up of many monosaccharides (>10). There are 3 main classes of polysaccharides: starch, glycogen, and most fibers. The following sections will describe the structural similarities and differences between the 3 classes of polysaccharides that are divided in the figure below.

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Subsections:

Starch

Starch is the storage form of glucose in plants. There are two forms of starch (shown in the figures below): amylose and amylopectin. Structurally they differ in that amylose is a linear polysaccharide (Figure 2.1511), whereas amylopectin is branched (Figure 2.1512).

Figure 2.1511 Structure of amylose

Figure 2.1512 Structure of amylopectin

Amylopectin is more common than amylose (4:1 ratio on average) in starch1,2. Some starchy foods include grains, root crops, tubers, and legumes.

References & Links

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Glycogen

Glycogen is similar to starch in that it is a storage form of glucose. Glycogen, however, is the carbohydrate storage form in animals, rather than plants. It is even more highly branched than amylopectin, as shown below.

Figure 2.1521 Structure of glycogen

The advantage of glycogen's highly branched structure is that the multiple ends (shown in red above) are where enzymes start to cleave off glucose molecules. As a result, with many ends available, it can provide glucose much more quickly to the body than it could if it was a linear molecule like amylose with only two ends. Although glycogen is characteristically found in muscle tissue (meats), we consume almost no glycogen, because it is rapidly broken down by enzymes in animals after slaughter1.

References & Links

1. Whitney E, Rolfes SR. (2008) Understanding Nutrition. Belmont, CA: Thomson Wadsworth.

Fiber

The simplest definition of fiber is indigestible matter. Indigestible means that it survives digestion in the small intestine and reaches the large intestine.

There are 3 major fiber classifications1:

Dietary Fiber - non-digestible carbohydrates and lignin that are intrinsic and intact in plants

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Functional Fiber - isolated, non-digestible carbohydrates that have beneficial physiological effects in humans

Total Fiber - dietary fiber + functional fiber

The differences between dietary and functional fiber are compared in the table below: Table 2.1531 Differences between dietary fiber and functional fiber

Dietary fiber is always intact in plants, whereas functional fiber can be isolated, extracted or synthesized. Functional fiber is only carbohydrates, while dietary fiber also includes lignins. Functional fiber can be from plants or animals, while dietary fiber is only from plants.

Functional fiber must be proven to have a physiological benefit, while dietary fiber does not. The reason behind the non-digestibility of fiber is the unique glycosidic bonds that link the individual monosaccharide units; the glycosidic bonds in fiber cannot be broken by our digestive enzymes.

Fiber can be classified by its physical properties. In the past, fibers were commonly referred to as soluble and insoluble. This classification distinguished whether the fiber was soluble in water. However, this classification is being phased out in the nutrition community. Instead, most fibers that would have been classified as insoluble fiber are now referred to as non- fermentable and/or non-viscous and soluble fiber as fermentable, and/or viscous because these better describe the fiber's characteristics2. Fermentable refers to whether the bacteria in the colon can ferment or degrade the fiber into short chain fatty acids and gas. Viscous refers to the capacity of certain fibers to form a thick gel-like consistency.

The following table lists some of the common types of fiber and provides a brief description about each.

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Table 2.1532 Common types of non-fermentable, non-viscous (insoluble) fiber

Table 2.1533 Common types of fermentable, viscous (soluble) fiber

The following table gives the percentage of total dietary fiber in 5 foods. Table 2.1534 Total dietary fiber (as percent of sample weight)3

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The table below shows the amount of non-fermentable, non-viscous fiber in these same five foods.

Table 2.1535 Non-viscous fiber (as percent of sample weight)3

The table below shows the amount of fermentable, viscous fiber in these same five foods.

Table 2.1536 Viscous Fiber (as percent of sample weight)3

tr = trace amounts

Foods that are good sources of non-fermentable, non-viscous fiber include whole wheat, whole grain cereals, broccoli, and other vegetables. This type of fiber is believed to decrease the risk of constipation and colon cancer, because it increases stool bulk and reduces transit time4. This reduced transit time theoretically means shorter exposure to consumed carcinogens in the intestine, and thus lower cancer risk.

Fermentable, viscous fiber can be found in oats, rice, psyllium seeds, soy, and some fruits. This type of fiber is believed to decrease blood cholesterol and sugar levels, thus also lowering the risk of heart disease and diabetes, respectively4. Its viscous nature slows the absorption of glucose preventing blood glucose from spiking after consuming carbohydrates. It lowers blood cholesterol levels primarily by binding bile acids, which are made from cholesterol, and causing them to be excreted. As such, more cholesterol is used to synthesize new bile acids.

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References & Links

92: 175-186.

Proteins

Proteins are another major macronutrient that, like carbohydrates, are made up of small repeating units. But instead of sugars, proteins are made up of amino acids. In the following sections, you will learn more about how proteins are synthesized and why they are important in the body.

Subsections:

Amino Acids

Similar to carbohydrates, proteins contain carbon (C), hydrogen (H), and oxygen (O). However, unlike carbohydrates (and lipids) proteins also contain nitrogen (N). Proteins are made up of smaller units called amino acids. This name, amino acid, signifies that each contains an amino (NH₂) and carboxylic acid (COOH) groups. The only structural difference in the 20 amino acids is the side group represented by the R below.

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Fig 2.211 Structure of an amino acid

To illustrate the differences in the side group we will consider glycine and alanine, the two simplest amino acids. For glycine, the R group is hydrogen (H), while in alanine the R group is a methyl (CH₃). The structures of these two amino acids are shown below.

Figure 2.212 Structure of glycine

Figure 2.213 Structure of alanine

Individual amino acids are joined together using a peptide bond (green) and is shown in the figure below. You might note that the formation of a peptide bond is a dehydration reaction (a reaction that creates a link between two molecules through the loss of a molecule of water).

This is the same basic reaction that links monosaccharides into more complex carbohydrates.

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Figure 2.214 Peptide bond formation1

In addition to dipeptides, amino acids can also come together to form tripeptides (three amino acids), oligopeptides (3-10 amino acids), and polypeptides (10 or more amino acids). A polypeptide is a chain of amino acids as shown below.

Figure 2.216 A polypeptide chain2

References & Links

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Protein Synthesis

Protein synthesis is a process critical to life. It is a cellular-based process that makes the proteins that are necessary to keeping each of our cells alive and functional. The process of protein synthesis (making protein) is not as simple as stringing together amino acids to form a polypeptide. As shown below, this is a fairly involved process. DNA contains the genetic code that is used as a template to create mRNA in a process known as transcription. The mRNA then moves out of the nucleus into the cytoplasm where it serves as the template for the process of translation, where tRNAs bring in individual amino acids that are bonded together to form a polypeptide.

Figure 2.221 The process of creating a polypeptide1

Tiny, intracellular structures, known as ribosomes, assist with translation. After translation, the polypeptide can be folded or gain structure as shown below and will be discussed in the next subsection (Protein Structure).

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Figure 2.222 Protein synthesis and processing

These videos do an excellent job of showing and explaining how protein synthesis occurs.

Required Web Links Video: Transcription (1:49) Video: Translation (2:05)

References & Links

Videos

Transcription - http://www.youtube.com/watch?v=5MfSYnItYvg Translation - http://www.youtube.com/watch?v=8dsTvBaUMvw

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Protein Structure

There are four levels of protein structure. Primary structure is the linear polypeptide chain. Secondary structure occurs when hydrogen bonding between amino acids in the same polypeptide chain causes the formation of structures such as beta-pleated sheets and alpha- helices. Tertiary structure, a three-dimensional folding of the polypeptide chain, occurs as a result of an attraction between different amino acids of the polypeptide chain and interactions between the different secondary structures. Finally, certain proteins contain quaternary structure where multiple polypeptide chains are bonded together to form a larger molecule.

Hemoglobin, the protein that binds oxygen in our red blood cells, is an example of a protein with quaternary structure. The figure below illustrates the different levels of protein structure.

Figure 2.231 Different Protein Structures1

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This video does a nice job of illustrating and explaining the different protein structures.

Required Web Link

Video: Protein Structure (0:52)

References & Links

1. "225 Peptide Bond-01" by OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. Licensed under CC BY 3.0 via Commons - https://commons.wikimedia.org/wiki/File:225_Peptide_Bond- 01.jpg#/media/File:225_Peptide_Bond-01.jpg

Video

Protein Structure - http://www.youtube.com/watch?v=lijQ3a8yUYQ

Protein Functions

There are various functions of proteins in the body that are described below.

Structural

Proteins, such as collagen, serve as the scaffolding of the body, and thus are important for the structure of tissues.

Figure 2.241 Triple-helix structure of collagen1

Enzymes

We will discuss a number of enzymes throughout this class, and the vast majority are proteins. An enzyme catalyzes (enhances the rate) of a chemical reaction. The key part of an enzyme is its "active site". The active site is where a compound to be acted on, known as a substrate, enters. Enzymes are specific for their substrates; they do not catalyze reactions on any random compounds floating by. You might have heard the "lock and key" analogy used for enzymes and substrates, respectively.

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After the substrate enters the active site and binds, the enzyme slightly changes shape (conformation). The enzyme then catalyzes a reaction that, in the example below, splits the substrate into two parts. The products of this reaction are released and the enzyme returns to its native or original shape. It is then ready to catalyze another reaction. The figure and video below nicely illustrate the function of an enzyme.

Figure 2.242 The function of enzymes2

Required Web Link

Video: Enzymes (0:49)

Enzymes’ names commonly end in -ase, and many are named for their substrate. For example, the enzyme amylase cleaves bonds found in amylose and amylopectin.

Hormones

Many hormones are proteins. A hormone is a compound that is produced in one tissue, released into circulation, then has an effect on a different organ. Most hormones are produced from several organs, collectively known as endocrine organs. Insulin is an example of a hormone that is a protein.

Required Web Link

Video: Hormones (1:02)

Fluid Balance

Proteins help to maintain the balance between fluids in the plasma and the interstitial fluid. Interstitial fluid is the fluid that surrounds cells. Interstitial fluid and plasma (fluid part of blood) are the two components of extracellular fluid, or the fluid outside of cells. The following figure illustrates the exchange of fluid between interstitial fluid and plasma.

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Figure 2.243 Interstitial Fluid and plasma3

Acid-Base Balance

Proteins serve as buffers, meaning that they help to prevent the pH of the body from getting too high or too low.

Transport

Transport proteins move molecules through circulation or across cell membranes. One example is hemoglobin that transports oxygen through the body. We will see a number of other examples as we move through class.

Immune Function

Antibodies are proteins that recognize antigens (foreign substances that generate antibody or inflammatory response) and bind to and inactivate them. Antibodies are important in our ability to ward off disease.

Other Functions

Proteins can also serve as neurotransmitters and can be used for energy by forming glucose through gluconeogenesis.

References & Links

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Videos

Enzymes - http://www.youtube.com/watch?v=cbZsXjgPDLQ Hormones - http://www.youtube.com/watch?v=kIPYVV4aThM

Types of Amino Acids

There are 20 amino acids our body uses to synthesize proteins. These amino acids can be classified as essential, non-essential, or conditionally essential. The table below shows how the 20 amino acids are classified.

Table 2.251 Essential, conditionally essential, and nonessential amino acids1

The body cannot synthesize nine amino acids. Thus, it is essential that these are consumed in the diet. As a result, these amino acids are known as essential amino acids, or indispensable amino acids. As an example of how amino acids were determined to be essential, Dr. William C. Rose at the University of Illinois discovered that threonine was essential by feeding different diets to graduate students at the university as described in the following link.

Required Web Link

Discovery of Threonine by William C. Rose

Non-essential, or dispensable, amino acids can be made in our body, so we do not need to consume them. Conditionally essential amino acids become essential for individuals in certain situations. An example of a condition when an amino acid becomes essential is the disease phenylketonuria (PKU). Individuals with PKU have a mutation in the enzyme phenylalanine hydroxylase, which normally adds an alcohol group (OH) to the amino acid phenylalanine to form tyrosine as shown below.

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Figure 2.251 Phenylketonuria (PKU) results from a mutation in the enzyme phenylalanine hydroxylase2,3

Since tyrosine cannot be synthesized by people with PKU, it becomes essential for them. Thus, tyrosine is a conditionally essential amino acid. Individuals with PKU have to eat a very low protein diet and avoid the alternative sweetener aspartame, because it can be broken down to phenylalanine. If individuals with PKU consume too much phenylalanine, phenylalanine and its metabolites, can build up and cause brain damage and severe mental retardation. The drug Kuvan was approved for use with PKU patients in 2007 who have low phenylalanine hydroxylase activity levels. You can learn more about this drug using the link below.

Required Web Link

Kuvan

References & Links

Links

Discovery of Threonine by William C. Rose - http://www.jbc.org/content/277/37/e25.full Kuvan - http://www.kuvan.com/

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Amino Acid Structures

It is a good idea to have a general idea of the structure of the different amino acids and to be able to recognize them as amino acids. You are not expected to memorize these structures.

Often, I’ll say the name of particular amino acids, and many students aren’t aware that it’s an amino acid. For example, around Thanksgiving, many of us have heard about tryptophan associated with turkey, but how many people know that tryptophan is actual a single amino acid?

Structurally, all amino acids have nearly the same base structure. They are all composed of an

-carbon, an amino group, a carboxyl group, and a side chain.

Figure 2.261 Basic structure for all amino acids1

Each amino acid differs only by its side chain, as show in Figure 2.262 (on the next page). Notice how the only difference between each amino acid is in its side chain (highlighted in pink.)

You may hear someone talk about the branched-chain amino acids (BCAAs), which are a common nutritional supplement. While their effect on athletic performance is in question, BCAAs provide several metabolic and physiologic roles2. Metabolically, BCAAs promote protein synthesis and turnover, signaling pathways, and metabolism of glucose. Additionally, the oxidation of BCAAs may increase fatty acid oxidation and play a role in obesity.

Physiologically, BCAAs take on roles in the immune system and in brain function3. Of the 20 amino acids found in the human body, only isoleucine, leucine, and valine are classified as BCAAs.

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Figure 2.262 Amino acid structures for the 20 amino acids found in the human body1

References & Links

35

Protein Quality

Proteins can be classified as either complete or incomplete. Complete proteins provide adequate amounts of all nine essential amino acids. Animal proteins such as meat, fish, milk, and eggs are good examples of complete proteins. Incomplete proteins do not contain adequate amounts of one or more of the essential amino acids. For example, if a protein doesn't provide enough of the essential amino acid leucine it would be considered incomplete. Leucine would be referred to as the limiting amino acid, because there is not enough of it for the protein to be complete. Most plant foods are incomplete proteins, with a few exceptions such as soy. The table below shows the limiting amino acids in some plant foods.

Table 2.271 Limiting amino acids in some common plant foods1

Complementary Proteins

Even though most plant foods do not contain complete proteins, it does not mean that they should be sworn off as protein sources. It is possible to pair foods containing incomplete proteins with different limiting amino acids to provide adequate amounts of the essential amino acids. These two proteins are called complementary proteins, because they supply the amino acid(s) missing in the other protein. A simple analogy would be that of a 4 piece puzzle. If one person has 2 pieces of a puzzle, and another person has 2 remaining pieces, neither of them have a complete puzzle. But when they are combined, the two individuals create a complete puzzle.

Figure 2.271 Complementary proteins are kind of like puzzle pieces

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Two examples of complementary proteins are shown below.

Peanut Butter and Jelly Sandwich Red Beans and Rice

Figure 2.272 Two complementary protein examples2,3

It should be noted that complementary proteins do not need to be consumed at the same time or meal. It is currently recommended that essential amino acids be met on a daily basis, meaning that if a grain is consumed at one meal, a legume could be consumed at a later meal, and the proteins would still complement one another4.

Measures of Protein Quality

How do you know the quality of the protein in the foods you consume? The protein quality of most foods has been determined by one of the methods below.

Biological Value (BV) - (grams of nitrogen retained / grams of nitrogen absorbed) x 100

Protein Efficiency Ratio (PER) - (grams of weight gained / grams of protein consumed) This method is commonly performed in growing rats.

Chemical or Amino Acid Score (AAS) - (Test food limiting essential amino acid (mg/g protein) / needs of same essential amino acid (mg/g protein))

Protein Digestibility Corrected Amino Acid Score (PDCAAS) - (Amino Acid Score x Digestibility) This is the most widely used method and was preferred by the Food and Agriculture Organization and World Health Organization (WHO) until recently5,6.

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The following table shows the protein quality measures for some common foods. Table 2.272 Measures of protein quality5

*PDCAAS scores are truncated (cut off) at 100. These egg and milk scores are actually 118 and 121 respectively.

The Food and Agricultural Organization (FAO) recently recommended that PDCAAS be replaced with a new measure of protein quality, the Digestible Indispensable Amino Acid Score (DIAAS). “DIAAS is defined as: DIAAS % = 100 x [(mg of digestible dietary indispensable amino acid in 1 g of the dietary protein) / (mg of the same dietary indispensable amino acid in 1g of the reference protein)].” Ideal digestibility should be utilized to determine the digestibility in DIAAS; ideally in humans, but if not possible in growing pigs or rats6.

The main differences between DIAAS and PDCAAS are:

How do I find out the protein quality of what I'm eating and identify complementary proteins?

Nutrition Data is a useful resource for determining protein quality and identifying complementary proteins. To use the site, go to www.nutritiondata.com, type in the name of the food you would like to know about in the search bar and hit ‘Enter’. When you have selected your food from the list of possibilities, you will be given information about this food.

Included in this information is the Protein Quality section. This will give you an amino acid score and a figure that illustrates which amino acid(s) is limiting. If your food is an incomplete protein, you can click "Find foods with a complementary profile". This will take you to a list of dietary

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choices that will provide complementary proteins for your food. You can read more about this option in the link below.

Required Web Link

Nutrition Data: Protein Quality

References & Links

Links

NutritionData - http://www.nutritiondata.com/

NutritionData: Protein Quality - http://nutritiondata.self.com/help/analysis-help#protein-quality

Protein-Energy Malnutrition

Protein deficiency rarely occurs alone. Instead it is often coupled with insufficient energy intake. As a result, the condition is called protein-energy malnutrition (PEM). This condition is not common in the U.S., but is more prevalent in less developed countries. Kwashiorkor and marasmus are the two forms of protein energy malnutrition. They differ in the severity of energy deficiency as shown in the figure below.

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Figure 2.281 The 2 types of protein-energy malnutrition

Kwashiorkor is a Ghanaian word that means "the disease that the first child gets when the new child comes1." The characteristic symptom of kwashiorkor is a swollen abdomen. Energy intake could be adequate, but protein consumption is too low.

Figure 2.282 A child suffering from kwashiorkor2

The video below does a nice job showing the symptoms of the condition.

Required Web Link

Video: Kwashiorkor (1:17)

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Marasmus means "to waste away" or "dying away", and thus occurs in individuals who have severely limited energy intakes.

Figure 2.283 Two individuals suffering from marasmus3

The video below shows individuals suffering from this condition.

Required Web Link

Video: Marasmus (2:24)

References & Links

Videos

Kwashiorkor - http://www.youtube.com/watch?v=eTU3iPWAWXg Marasmus - https://www.youtube.com/watch?v=LDCi3eda4WM

Lipids

Lipids, commonly referred to as fats, have a poor reputation among some people, in that "fat free" is often synonymous with healthy. We do need to consume certain fats and we should try to incorporate some fats into our diets for their health benefits. However, consumption of certain fats is also associated with greater risk of developing chronic disease(s). In this section, we will dive deeper into fats and why they do not need to be feared altogether.

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Subsections:

How Does Fat Differ from Lipids?

The answer you receive from this question will depend on who you ask, so it is important to have an understanding of lipids and fats from a chemical and nutritional perspective.

To a chemist, lipids consist of:

These compounds are grouped together because of their structural and physical property similarities. For instance, all lipids have hydrophobic (water-fearing) properties. Chemists further separate lipids into fats and oils based on their physical properties at room temperature:

Fats are solid at room temperature

Oils are liquid at room temperature

From a nutritional perspective, the definition of lipids is the same. The definition of a fat differs, however, because nutrition-oriented people define fats based on their caloric contribution rather than whether they are solid at room temperature. Thus, from a nutrition perspective:

Fats are triglycerides, fatty acids, and phospholipids that provide 9 kcal/g.

The other difference is that from a caloric perspective, an oil is a fat. For example, let's consider olive oil. Clearly, it is an oil according to a chemist definition, but from a caloric standpoint it is a fat because it provides 9 kcal/g.

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The following sections will discuss the different lipid classes introduced above in detail.

No References

Fatty acids are lipids themselves, and they are also components of triglycerides and phospholipids. Like carbohydrates, fatty acids are made up of carbon (C), hydrogen (H), and oxygen (O).

On one end of a fatty acid is a methyl group (CH₃) that is known as the methyl or omega end. On the opposite end of a fatty acid is a carboxylic acid (COOH). This end is known as the acid or alpha end. The figure below shows the structure of fatty acids.

Figure 2.321 Structure of a saturated fatty acid

There are a number of fatty acids in nature that we consume that differ from one another in three ways:

Fatty acids differ in their carbon chain length (number of carbons in the fatty acid). Most fatty acids contain somewhere between 4-24 carbons, with even numbers (i.e. 8, 18) of carbons occurring more frequently than odd numbers (i.e. 9, 19). Fatty acids are classified as short-chain fatty acids, medium-chain fatty acids, and long-chain fatty acids based on their carbon chain length using the criteria shown in the table below.

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Table 2.321 Fatty acid classification

Carbon chain length also impacts the physical properties of the fatty acid. As the number of carbons in a fatty acid chain increases, so does the melting point. Shorter chain fatty acids are more likely to be liquid, while longer chain fatty acids are more likely to be solid at room temperature (20-25oC, 68-77oF).

Saturation/Unsaturation

A saturated fatty acid is one that contains the maximum number of hydrogens possible, and no carbon-carbon double bonds. Carbon normally has four bonds to it. Thus, a saturated fatty acid has hydrogens at every position except carbon-carbon single bonds and carbon-oxygen bonds on the acid end.

Unsaturation means the fatty acid doesn't contain the maximum number of hydrogens on each of its carbons. Instead, unsaturated fatty acids contain a carbon-carbon double bond and only 1 hydrogen off each carbon. The simplest example of unsaturation is a monounsaturated fatty acid. Mono means one, so these are fatty acids with one degree of unsaturation, or one double bond.

Any fatty acid that has two or more double bonds is considered a polyunsaturated fatty acid. As you may remember from the polysaccharide section, poly means many. A simple example of a polyunsaturated fatty acid is linoleic acid (shown below).

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Figure 2.322 Structure of saturated, monounsaturated, and polyunsaturated fatty acid2.

Double Bond Configuration (Shape)

Double bonds in unsaturated fatty acids are in one of two structural orientations: cis or trans. In a trans orientation, the hydrogens on the carbons involved in the double bond are opposite of one another. In the cis orientation, the hydrogens are on the same side of the bond. Steric hindrance in the cis orientation causes the chain to take on a more bent shape.

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Figure 2.323 Cis and trans structural conformations of a monounsaturated fatty acid

Most natural unsaturated fatty acids are in the cis conformation. As can be seen in Figure 2.327, the cis fatty acids have a more of kinked shape, which means they do not pack together as well as the saturated or trans fatty acids. As a result, the melting point is much lower for cis fatty acids compared to trans and saturated fatty acids.

There are some naturally occurring trans fatty acids, such as conjugated linoleic acid (CLA), in dairy products. However, for the most part, trans fatty acids in our diets are not natural; instead, they have been produced synthetically. The primary source of trans fatty acids in our food supply is partially hydrogenated vegetable oil. The 'hydrogenated' means that the oil has gone through the process of hydrogenation. Hydrogenation, like the name implies, is the addition of hydrogen. If an unsaturated fatty acid is completely hydrogenated it would be converted to a saturated fatty acid as shown in Figure 3.324.

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Figure 2.324 Fatty acid hydrogenation

However, complete hydrogenation isn't/wasn't always desirable, thus partially hydrogenated vegetable oil became widely used. To visualize the difference in the amount of hydrogenation consider the difference between tub margarine and stick margarine.

Stick margarine is more fully hydrogenated giving it a more solid texture. This is one of the two reasons to hydrogenate, to get a more solid texture. The second reason is that it makes it more shelf-stable, because the double bond(s) of unsaturated fatty acids are susceptible to oxidation, which causes them to become rancid.

Partial hydrogenation causes the conversion of cis to trans fatty acids along with the formation of some saturated fatty acids. Originally, it was thought that trans fatty acids would be a better alternative to saturated fat (think margarine vs. butter). However, it turns out that trans fat is actually worse than saturated fat in altering biomarkers associated with cardiovascular disease. Trans fat increases LDL and decreases HDL levels, while saturated fat increased LDL without altering HDL levels. But this does not mean that butter is a better choice than margarine as described in the first link. The FDA revoked Generally Recognized as Safe (GRAS) status of partially hydrogenated vegetable oil as described in the second link, and is requiring its use to be phased out by 2018. After that point, permission will need to be requested to use them in foods.

Required Web Links

Butter vs. Margarine: Which is better for my heart? FDA to Limit Trans Fats in Foods

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References & Links

Links

Butter vs. Margarine: Which is better for my heart? - http://www.mayoclinic.org/butter-vs-margarine/expert- answers/FAQ-20058152

FDA to Limit Trans Fats in Foods - http://www.nbcnews.com/health/health-news/fda-limit-trans-fats-food- n376266

Fatty Acid Naming & Food Sources

We will look at two naming systems used for fatty acids:

Omega Nomenclature

For omega nomenclature, you need to know 3 things:

We will again consider the same fatty acid.

Figure 2.331 Omega Nomenclature

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Instead of an omega prefix as seen in the figure, the prefix n- (i.e. n-9) is also commonly used. Therefore, the fatty acid in Figure 2.331 would be named 18:1 n-9.

If naming a saturated fatty acid, then the omega nomenclature is not added to the end of the name. If it is an 18-carbon saturated fatty acid, then it would be named 18:0.

Common Names

The common names of fatty acids are something that, for the most part, have to be learned/memorized. The common name of the fatty acid we have been naming in this section is oleic acid.

Figure 2.332 Oleic acid

However, it can also be called oleate. The only difference is that it has been ionized to form a salt (shown below; there is now a charge on the red oxygen atom). This is what the -ate ending indicates and the two names are used interchangeably.

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Figure 2.333 Oleate

The table below gives the common names and food sources of some common fatty acids. Table 2.331 Common names of fatty acids2

The NutritionData link below can help you identify foods that are high in a specific fatty acid.

Required Web Link

NutritionData: Fatty Acids

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Food Sources of Fatty Acids

After going through this wide array of fatty acids, you may be wondering where they are found in nature. The figure below shows the fatty acid composition of certain oils and oil-based foods. As you can see, most foods contain a mixture of fatty acids. Stick margarine is the only product in the figure that contains an appreciable amount of trans fatty acids. Corn, walnut, and soybean are rich sources of n-6 polyunsaturated fatty acids (a.k.a. omega-6 fatty acids), while flax seed is fairly unique among plants in that it is a good source of n-3 polyunsaturated fatty acids (a.k.a. omega-3 fatty acids). Canola and olive oil are rich sources of monounsaturated fatty acids. Lard, palm oil, butter and coconut oil all contain a significant amount of saturated fatty acids.

Figure 2.335 Fatty acid composition of foods and oils3

References & Links

Links

Nutrition Data: Fatty Acids - http://nutritiondata.self.com/topics/fatty-acids

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Essential Fatty Acids & Eicosanoids

The two essential fatty acids are:

linoleic acid (omega-6 fatty acid)

These fatty acids are essential because we cannot synthesize them. This is because we do not have an enzyme capable of adding a double bond (desaturating) beyond the omega-9 carbon counting from the alpha end (the omega-6 and 3 positions). The structures of the two essential fatty acids are shown below.

Figure 2.341 Linoleic acid1

Figure 2.342 Alpha-linolenic acid2

However, we do possess enzymes that can take the essential fatty acids, elongate them (add two carbons to them), and then further desaturate them (add double bonds) to other omega-6 and omega-3 fatty acids. Thus, there are 2 families of fatty acids that the majority of polyunsaturated fatty acids fit into as shown below.

The same enzymes are used for both omega-6 and omega-3 fatty acids. However, we cannot convert omega-3 fatty acids to omega-6 fatty acids, or omega-6 fatty acids to omega-3 fatty acids. Among these families, the omega-3 fatty acid, eicosapentaenoic acid (EPA), and the omega-6 fatty acids, dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA), are used to form compounds known as eicosanoids. These 20 carbon fatty acid derivatives are biologically active in the body (like hormones, but they act locally in the tissue they are produced).

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There are four classes of eicosanoids:

The difference in the effects and outcomes of omega-6 and omega-3 fatty acid intake is primarily a result of the eicosanoids produced from them. Omega-6 fatty acid derived eicosanoids are more inflammatory than omega-3 fatty acid derived eicosanoids. As a result, omega-3 fatty acids are considered anti-inflammatory because replacing the more inflammatory omega-6 fatty acid derived eicosanoids with omega-3 fatty acid derived eicosanoids will decrease inflammation

You have probably heard that you should get more omega-3s in your diet, and in general polyunsaturated fatty acids are considered healthy. However, since omega-3 fatty acids are competing for the same enzymes as omega-6 fatty acids, and because the omega-6 fatty acids are more inflammatory, consuming too many omega-6s is probably more detrimental than helpful. As a result, many people talk about the omega-3:6 fatty acid ratio in peoples' diets. For most Americans, the ratio is believed to be too high, at almost 10-20 times more omega-6 fatty acids than omega-3 fatty acids10. The table below shows good food sources of some selected omega-3 and omega-6 fatty acids.

Table 2.341 Good food sources of selected omega-3 and omega-6 fatty acids

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Essential Fatty Acid Deficiency

Essential fatty acid deficiency is rare and unlikely to occur, but the symptoms include:

References & Links

Links

Fish Oil Claims Not Supported by Research - http://well.blogs.nytimes.com/2015/03/30/fish-oil-claims-not- supported-by-research/

Triglycerides

Triglycerides are the most common lipid in our bodies and in the foods we consume. Fatty acids are not typically found free in nature, instead they are found in triglycerides. Breaking down the name triglyceride tells a lot about their structure. "Tri" refers to the three fatty acids, "glyceride" refers to the glycerol backbone that the three fatty acids are bonded to. Thus, a monoglyceride contains one fatty acid, a diglyceride contains two fatty acids. Triglycerides perform the following functions in our bodies:

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A triglyceride is formed by three fatty acids being bonded to glycerol as shown below.

Figure 2.351 Triglyceride formation

When a fatty acid is added to the glycerol backbone, this process is called esterification. This process is so named, because it forms an ester bond between each fatty acid and the glycerol. Three molecules of water are also formed during this process as shown below.

Figure 2.352 Esterification of three fatty acids to glycerol

A stereospecific numbering (sn) system is used to number the three fatty acids in a triglyceride sn-1, sn-2, and sn-3 respectively. A triglyceride can also be simply represented as a polar (hydrophilic) head, with 3 nonpolar (hydrophobic) tails, as shown in Figure 2.353.

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Figure 2.353 Stereospecific numbering (sn) of triglycerides

The three fatty acids in a triglyceride can be the same or can each be a different fatty acid. A triglyceride containing different fatty acids is known as a mixed triglyceride. An example of a mixed triglyceride is shown below.

Figure 2.354 Structure of a mixed triglyceride

No References

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Phospholipids

Phospholipids are similar in structure to triglycerides, with the only difference being a phosphate group and nitrogen-containing compound in the place of a fatty acid.

Figure 2.361 Structure of a phospholipid, R represents the different fatty acids, X represents the nitrogen-containing compound off of the phosphate group1

The best-known phospholipid is phosphatidylcholine (a.k.a. lecithin). As you can see in the structure below, it contains a choline off of the phosphate group.

Figure 2.362 Structure of phosphatidylcholine (lecithin)

However, you will not normally find phospholipids arranged like a triglyceride, with the 3 tails opposite of the glycerol head. This is because the phosphate/nitrogen tail of the phospholipid is polar. Thus, the structure will look like those in Figures 2.363 & 2.364.

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Figure 2.363 Structure of phosphatidylcholine (lecithin)2

Figure 2.364 Structure of phosphatidylcholine (lecithin)3

Similar to triglycerides, phospholipids are also represented as a hydrophilic head with two hydrophobic tails as shown below.

Figure 2.365 Schematic of a phospholipid

Phospholipid Functions

Because its structure allows it to be at the interface of water-lipid environments, there are two main functions of phospholipids:

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Number 1 in the figure below is a cell's lipid bilayer, while 2 is a micelle that is formed by phospholipids to assist in emulsification.

Figure 2.366, 1 - lipid bilayer, 2 - micelle4

Key Component of Cells' Lipid Bilayers

Phospholipids are an important component of the lipid bilayers of cells. A cross section of a lipid bilayer is shown below. The hydrophilic heads are on the outside and inside of the cell; the hydrophobic tails are in the interior of the cell membrane.

Figure 2.367 Phospholipids in a lipid bilayer. The blue represents the watery environment on both sides of the membrane, while the dark green represents the hydrophobic environment in between the membranes5

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Emulsification

As emulsifiers, phospholipids help hydrophobic substances mix in a watery environment. It does this by forming a micelle as shown below. The hydrophobic substance is trapped on the interior of the micelle away from the aqueous environment.

Figure 2.368 Structure of a micelle6

As a result, it can take a hydrophobic liquid (oil) and allow it to mix with hydrophilic liquid (water).

In a practical sense, the micelle is an ideal transportable particle for our blood stream. Since our blood is an aqueous solution, transport of nonpolar (hydrophobic) substances, like fat, cholesterol and fat-soluble vitamins (like vitamin D), can be a problem. The solution: micelles can function like tiny delivery trucks, transporting nonpolar substances through our circulatory system to our cells as they are needed.

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Figure 2.369 How an emulsion can allow the dispersion of a hydrophobic substance (II) into a hydrophilic environment (I) as shown in D7

Foods rich in phosphatidylcholine include: egg yolks, liver, soybeans, wheat germ, and peanuts8. Egg yolks serve as an emulsifier in a variety of recipes. However, your body can make all the phospholipids that it needs, so they do not need to be consumed (not essential).

References & Links

61

Sterols

The last category of lipids are the sterols. Their structure is quite different from the other lipids because sterols are made up of a number of carbon rings. The generic structure of a sterol is shown below.

Figure 2.371 Generic structure of a sterol

The primary sterol that we consume is cholesterol. The structure of cholesterol is shown below.

Figure 2.372 The carbon ring structure of cholesterol1

Cholesterol is frequently found in foods as a cholesterol ester, meaning that there is a fatty acid attached to it. The structure of a cholesterol ester is shown below.

Figure 2.373 Structure of a cholesterol ester

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All sterols have a similar structure to cholesterol. Cholesterol is only found in foods of animal origin. If consumers were more knowledgeable, intentionally misleading practices, such as

labeling a banana “cholesterol free”, would not be as widespread as they currently are today.

Function

Although cholesterol has acquired the status of a nutritional "villain", it is a vital component of cell membranes, and is used to produce vitamin D, hormones, and bile acids. However, we do not need to consume any cholesterol from our diets (not essential) because our bodies have the ability to synthesize the required amounts. The figure below gives you an idea of the cholesterol content of a variety of foods.

Figure 2.374 The cholesterol content (mg) of foods4

There is neither bad nor good cholesterol, despite these descriptions being commonly used for LDL and HDL, respectively. Cholesterol is cholesterol. HDL and LDL contain cholesterol but are actually lipoproteins that will be described later in chapter 4.

References & Links

63

Chapter 3: Macronutrient Digestion

You probably do not think too much about what actually happens to the food you eat. This section will describe in depth how what you eat is digested. The desired end result for the learner will be an integrated understanding of the process. This will require higher levels of thinking, but will prove to be well worth it in the end.

Sections:

No References

Digestion is the process of breaking down food to be absorbed or excreted. There are two types of digestion in the body; mechanical and chemical. Mechanical digestion involves physically breaking food down into smaller pieces, usually through muscle contractions.

Chemical digestion uses enzymes or other chemicals to break of food into smaller nutrients. This generally involves the breaking of chemical bonds in the process.

Figure 3.11 A number of organs are involved in digestion, which collectively are referred to as the digestive system1.

Required Web Link

Video: Enzymes and Digestion

The gastrointestinal (GI or digestive) tract, the passageway through which our food travels, is a "tube within a tube." The trunk of our body is the outer tube and the GI tract is the interior tube, as shown below. Thus, even though the GI tract is within the body, the actual interior of the tract is technically outside of the body. This is because the contents have to be absorbed into the body. If it's not absorbed, it will be excreted and never enter the body itself. It’s as if you never consumed it.

Figure 3.12 The digestive tract, also known as the gastrointestinal tract, is a "tube within a tube"

The organs that form the gastrointestinal tract (e.g., mouth, esophagus, stomach, small intestine, large intestine (aka colon), rectum, and anus) come into direct contact with the food or digestive contents.

Figure 3.13 The gastrointestinal or digestive tract2

The journey through the gastrointestinal tract starts in the mouth and ends in the anus as shown below:

Mouth --> Esophagus --> Stomach --> Small Intestine --> Large Intestine --> Rectum --> Anus

In addition to the GI tract, there are a number of accessory organs (e.g. salivary glands, pancreas, gallbladder, and liver) that play an integral role in digestion. The accessory organs do not come directly in contact with food or digestive contents, but still play a crucial role in the digestive process.

Figure 3.14 Digestion accessory organs1

In addition to the digestive and accessory organs, there are a number of enzymes that are involved in digestion. We will go through each one in detail later, but this table should help give an overview of which enzymes are active at each location of the GI tract.

Table 3.11 Digestive enzymes

References & Links

.html

Video

Enzymes and Digestion - http://www.youtube.com/watch?v=bNMsNHqxszc

Mouth to the Stomach

Digestion begins in the mouth, both mechanically and chemically. Mechanical digestion in the mouth consists of mastication, or the chewing and grinding of food into smaller pieces. The salivary glands release saliva, mucus, and three enzymes: salivary amylase, lingual lipase, and lysozyme.

Figure 3.21 The mouth1

Salivary amylase cleaves the glycosidic bonds in the starch molecules, amylose and amylopectin. Overall however, this enzyme accounts for a minor amount of carbohydrate digestion.

Lysozyme helps break down bacteria cell walls to prevent a possible infection. Another enzyme, lingual lipase, is also released in the mouth. Although it is released in the mouth, it is most active in the stomach where it preferentially cleaves short-chain fatty acids. Lingual lipase has a small role in digestion in adults, but may be important for infants to help break down triglycerides in breast milk2.

Swallowing (a.k.a Deglutition)

Now that the food has been thoroughly chewed and formed into a bolus (a small rounded mass of chewed food), it can proceed down the throat to the next stop in digestion. It will move down the pharynx where it reaches a "fork in the road", with the larynx as one road and the esophagus as the other. The esophagus road leads to the stomach; this is the direction that food should go (see figure 3.22). The other road, through the larynx, leads to the trachea and ultimately the lungs. This is definitely not where you want your food or drink going, as this is the pathway for the air you breathe.

Figure 3.22 Cross section of face. The epiglottis covers larynx to prevent food and drink from entering the lungs3

Fortunately, our body was designed in such a way that a small flap, called the epiglottis, covers the opening to the trachea during swallowing. It directs the food down the correct road as shown below.

Figure 3.23 Epiglottis is like a traffic cop guiding food down the correct digestion road.

Esophagus

Before being correctly guided into the esophagus, the bolus of food will travel through the upper esophageal sphincter. Sphincters are circular muscles that are found throughout the gastrointestinal tract that essentially serve as gates between the different sections. Once in the esophagus, wave-like muscular movements, known as peristalsis, occur, as shown in the animation and video in the links below. Peristalsis occurs throughout the digestive tract with the purpose of moving food along the tract.

Required Web Links Peristalsis Animation Video: Peristalsis (0:57)

At the end of the esophagus, the bolus will encounter the lower esophageal sphincter, also known as the cardiac sphincter due to its proximity to the heart. This sphincter keeps the harmful acids of the stomach out of the esophagus. However, in many people this sphincter is leaky, which allows stomach acid to reflux, or creep up, the esophagus. Stomach acid is very acidic (has a low pH). The ruler below will give you an idea of just how acidic the stomach is. Notice that the pH of gastric (term used to describe the stomach) fluid is lower (more acidic) than any of the listed items besides battery acid.

Figure 3.24 pH of some common items4

The leaking of the very acidic gastric contents results in a burning sensation commonly referred to as "heartburn." If this occurs more than twice per week and is severe, the person may have gastroesophageal reflux disease (GERD). The following videos explain more about these conditions.

Required Web Links Video: Acid Reflux (1:28) Video: GERD 101 (0.55)

Table 3.21 Review of Chemical Digestion in the Mouth

References & Links

Link

Peristalsis - http://en.wikipedia.org/wiki/File:Peristalsis.gif

Videos

Peristalsis Animation - http://www.youtube.com/watch?v=o18UycWRsaA Acid Reflux - https://www.youtube.com/watch?v=SW-QfyDSY5I

GERD 101 - http://www.youtube.com/watch?v=FqdOvZkrSYk&feature=rec-lis-watch-cur_emp- farside_rn

Stomach

After going through the lower esophageal sphincter, food enters the stomach. Our stomach is involved in both chemical and mechanical digestion. Mechanical digestion occurs as the stomach churns and grinds food into a semisolid substance called chyme (partially digested food).

There are four main regions in the stomach: the cardia, fundus, body, and pylorus (see Figure

3.31 below). The cardia (or cardiac region) is the point where the esophagus connects to the stomach and through which food passes into the stomach. Located inferior to the diaphragm, above and to the left of the cardia, is the dome-shaped fundus. Below the fundus is the body, the main part of the stomach. The funnel-shaped pylorus connects the stomach to the duodenum. The wider end of the funnel, the pyloric antrum, connects to the body of the stomach. The narrower end is called the pyloric canal, which connects to the duodenum. The smooth muscle pyloric sphincter is located at this latter point of connection and controls stomach emptying. In the absence of food, the stomach deflates inward, and its mucosa and submucosa fall into a large fold called a rugae6. These rugae increase the surface area inside the stomach, which aids the digestive process.

Figure 3.31 The stomach has four major regions: the cardia, fundus, body, and pylorus. The addition of an inner oblique smooth muscle layer gives the muscularis the ability to vigorously churn and mix food6.

The lining of the stomach is made up of four different layers of tissue. For the purposes of this discussion, we will focus on only the innermost layer. The mucosa is the innermost layer of the stomach (closest to stomach cavity) as shown in the figure below.

Figure 3.32 The anatomy of the stomach1

The mucosa is not a flat surface. Instead, its surface is lined by gastric pits, as shown in the figure 3.33 below.

Figure 3.33 Gastric pits2

Gastric pits are indentations in the stomach's surface that are lined by four different types of cells (see figure 3.34 for names and locations).

Figure 3.34 Blowup of mucosa to show the structure of gastric pits1

The following video is a nice introduction to gastric pits and talks about chief and parietal cells that are covered in more detail below.

Required Web Link

Video: Gastric Pits (0:56)

At the bottom of the gastric pit are the gastric enteroendocrine cells (G cells) that secrete the hormone gastrin. Gastrin stimulates the parietal and chief cells that are found above the G cells. The chief cells secrete the pepsinogen. Pepsinogen is the inactive precursor that must be altered to form the active enzyme, pepsin. The parietal cells secrete hydrochloric acid (HCl), which lowers the pH of the gastric juice (water + enzymes + acid). The HCl also inactivates salivary amylase and catalyzes the conversion of the inactive pepsinogen to its active form, known as pepsin. Finally, at the top of the pits are the neck cells (specialized goblet cells) that secrete mucus to prevent the gastric juice from digesting or damaging the stomach mucosa3. The table below summarizes the actions of the different cells in the gastric pits.

Table 3.41 Cells involved in the digestive processes in the stomach

The figure below shows the action of all these different secretions in the stomach.

Figure 3.35 The action of gastric secretions in the stomach

To reiterate, the figure above illustrates that the neck cells of the gastric pits secrete mucus to protect the mucosa of the stomach from essentially digesting itself. Gastrin from the G cells stimulates the parietal and chief cells to secrete HCl and enzymes, respectively.

The HCl in the stomach denatures salivary amylase and other proteins by breaking down the structure and, thus, the function of it. HCl also converts pepsinogen to the active enzyme pepsin. Pepsin is a protease, meaning that it cleaves the peptide bonds in proteins. It breaks down the proteins in food into individual peptides (shorter segments of amino acids).

The chyme will then leave the stomach in small amounts and enter the small intestine via the pyloric sphincter (shown below). Full emptying of the stomach takes about 2-4 hours.

Figure 3.36 Cross section of the stomach showing the pyloric sphincter5

Table 3.32 Summary of chemical digestion in the stomach

References & Links

Video

Gastric Pits - http://www.youtube.com/watch?v=6hquzCXYlNg

Small Intestine

The small intestine is the primary site of digestion. It is divided into three sections: the duodenum, jejunum, and ileum (shown below). After leaving the stomach, the first part of the small intestine that chyme will encounter is the duodenum.

Figure 3.41 Three sections of the small intestine1

The small intestine consists of many layers, which can be seen in the cross section in Figure 3.42 below.

Figure 3.42 Cross section of the small intestine2

Examining these layers more closely, we are going to focus on the lining of the small intestine, known as the epithelium (see Figure 3.42 above), which comes into contact with the chyme and is responsible for absorption. The lumen is the name of the cavity that is considered “outside

the body” that chyme moves through.

The organization of the small intestine is in such a way that it contains circular folds and finger- like projections known as villi. The folds and villi are shown in the next few figures.

Figure 3.43 Folds in the small intestine2

Figure 3.44 Villi in the small intestine3

Figure 3.45 Villi line the surface of the small intestine2,4

If we were to zoom in even closer, we would be able to see that enterocytes (small intestine absorptive cells; a.k.a brush border cells) line villi as shown below. This layer is referred to as the mucosa, and is composed primarily of simple columnar epithelium.

Figure 3.46 Enterocytes line villi4

The side, or membrane, of the enterocyte that faces the lumen is not smooth either. It is lined with microvilli, and is known as the brush border membrane, as shown below.

Figure 3.47 Enterocyte, or small intestinal absorptive cell is lined with microvilli. This lined surface is referred to as the brush border membrane.

Together these features (folds + villi + microvilli) increase the surface area ~600 times versus if it was a smooth tube5. (Note: the symbol ~ is used in place of the word “approximately.” You will see it used other places in this text as well.) More surface area leads to more contact between the chyme and the enterocytes, and thus, increased absorption.

Finally, the surface of the cells on the microvilli are covered with proteins, which helps to catch a molecule-thin layer of water within itself. This layer, called the "unstirred water layer," has a

number of functions in absorption of nutrients, and will have a direct impact on fat absorption as we will see later6.

Figure 3.48 Unstirred water layer

Now that you have learned about the anatomy of the small intestine, the following subsections go through the different digestive processes that occur there.

Subsections:

References & Links

Digestive Hormones, Accessory Organs & Secretions

Before we go into the digestive details of the small intestine, it is important that you have a basic understanding of the anatomy and physiology of the following digestion accessory organs: pancreas, liver, and gallbladder. Digestion accessory organs assist in digestion, but are not part of the gastrointestinal tract. How are these organs involved?

Upon entering the duodenum, the chyme causes the release of two hormones from the small intestine: secretin and cholecystokinin (CCK) in response to acid and fat, respectively. These

hormones have multiple effects on different tissues. In the pancreas, secretin stimulates the secretion of bicarbonate (HCO₃), while CCK stimulates the secretion of digestive enzymes. The bicarbonate and digestive enzymes released together are collectively known as pancreatic juice, which travels to the small intestine, as shown below.

Figure 3.411 The hormones secretin and CCK stimulate the pancreas to secrete pancreatic juice1

In addition, CCK also stimulates the contraction of the gallbladder causing the secretion of stored bile into the duodenum.

Pancreas

The pancreas is found behind the stomach and just above the transverse colon (part of the large intestine discussed later in this chapter). It is a tadpole-shaped organ consisting of a head, body, and tail. It is a unique organ containing both endocrine and exocrine portions. The smaller, endocrine (hormone-producing) portions contain alpha, beta, delta, and PP cells that secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide respectively. These cells are clustered in groups known as pancreatic islets (traditionally referred to as the Islets of Langerhans). However, the vast majority of the pancreas is made up of grape-like clusters of exocrine cells known as acini (singular = acinus). The cells composing each acinus are known as acinar cells. These acinar cells are responsible for producing enzyme-rich pancreatic juice. Pancreatic juice is released into small ducts that continually merge to form a large main pancreatic duct which delivers pancreatic juice from the pancreas to the duodenum, merging with the common bile duct (from the liver & gallbladder) along the way. The release of pancreatic juice, and bile, is controlled by the hepatopancreatic sphincter. The following video does a nice job of showing and explaining the function of the different pancreatic cells.

Figure 3.412 The pancreas has a head, a body, and a tail. It delivers pancreatic juice to the duodenum through the pancreatic duct5.

Required Web Link

Video: The Pancreas (First 53 seconds)

In addition to pancreatic hormones and enzymes, the pancreas releases bicarbonate. Bicarbonate is a base (high pH) meaning that it can help neutralize an acid (such as gastric juice.) You can find sodium bicarbonate (NaHCO₃, baking soda) on the ruler below to get an idea of its pH.

Figure 3.413 pH of some common items2

The main digestive enzymes in pancreatic juice are listed in the table below. Their function will be discussed further in later subsections.

Table 3.411 Enzymes in pancreatic juice

Liver

The liver is the largest internal, and the most metabolically active, organ in the body. The figure below shows the liver and the other accessory organs position relative to the stomach.

Figure 3.414 Location of digestion accessory organs relative to the stomach3

The liver is made up two major types of cells. The primary liver cells are hepatocytes, which carry out most of the liver’s functions. Hepatic is another term for liver. For example, if you are going to refer to liver concentrations of a certain nutrient, these are often reported as hepatic concentrations. The other major cell type is the hepatic stellate (also known as Ito) cells. These are fat storing cells in the liver.

The liver's major role in digestion is to produce bile. This is a greenish-yellow fluid that is composed primarily of bile acids, but also contains cholesterol, phospholipids, and the pigments bilirubin and biliverdin. Bile acids are synthesized from cholesterol. The two primary bile acids are chenodeoxycholic acid and cholic acid. In the same way that fatty acids are found in the form of salts, these bile acids can also be found as salts. Because of this, these bile salts are often seen in texts with an (-ate) ending (chenodeoxycholate and cholate) indicating they are in the salt form.

Bile acids, much like phospholipids, have both hydrophobic and hydrophilic portions. This makes them excellent emulsifiers that are instrumental in fat digestion. Bile is then transported to the gallbladder.

Gallbladder

The gallbladder is a small, sac-like organ found just off the liver (see figure 3.413 above). Its primary function is to store and concentrate bile made by the liver. The bile is then transported to the duodenum through the common bile duct.

Why do we need bile?

Bile is important because fat is hydrophobic, but the environment in the lumen of the small intestine is watery. In addition, there is an unstirred water layer that fat must cross to reach the enterocytes in order to be absorbed.

Figure 3.415 Fat is not happy alone in the watery environment of the small intestine.

Triglycerides naturally form large triglyceride droplets to keep the interaction with the watery environment to a minimum. Picture the large droplets of cooking oil that form when you add it to water. This is inefficient for digestion, because enzymes cannot access the interior of the droplet. Bile acts as an emulsifier, or detergent. It, along with phospholipids, breaks the large triglyceride droplets into smaller triglyceride droplets that increase the surface area accessible for triglyceride digestive enzymes, as shown below.

Figure 3.416 Bile acids and phospholipids facilitate the production of smaller triglyceride droplets.

Secretin and CCK also control the production and secretion of bile. Secretin stimulates the flow of bile from the liver to the gallbladder. CCK stimulates the gallbladder to contract, causing bile to be secreted into the duodenum, as shown in Figure 3.417.

Figure 3.417 Secretion stimulates bile flow from liver; CCK stimulates the gallbladder to contract3

References & Links

.html

Video

The Pancreas - http://www.youtube.com/watch?v=j5WF8wUFNkI

Carbohydrate Digestion in the Small Intestine

The small intestine is the primary site of carbohydrate digestion. Pancreatic amylase is the primary carbohydrate digesting enzyme. Pancreatic amylase, like salivary amylase, cleaves the glycosidic bonds of carbohydrates, reducing them to simpler carbohydrates, such as glucose, maltose, maltotriose, and α-dextrin (an oligosaccharide containing 1 or more glycosidic bonds which pancreatic amylase unable to cleave1).

The pancreatic amylase products, along with the disaccharides sucrose and lactose, then move to the surface of the enterocyte.

Here, the brush border enzyme α-dextrinase starts working on α-dextrin, breaking off one glucose unit at a time. Three other brush border enzymes hydrolyze sucrose, lactose, and maltose into monosaccharides. Sucrase splits sucrose into one molecule of fructose and one molecule of glucose; maltase breaks down maltose into two glucose molecules; and lactase breaks down lactose into one molecule of glucose and one molecule of galactose2. Insufficient lactase can lead to lactose intolerance (discussed in a later chapter.) The products from these brush border enzymes are the single monosaccharides glucose, fructose, and galactose that are ready for absorption into the enterocyte1.

Figure 3.423 Disaccharidases on the outside of the enterocyte.

Figure 3.424 Carbohydrates are broken down into their monomers in a series of steps2.

References & Links

Protein Digestion in the Small Intestine

The small intestine is the major site of protein digestion by proteases (enzymes that cleave proteins). The pancreas secretes a number of proteases into the duodenum where they must be activated before they can cleave peptide bonds1. This activation occurs through an activation cascade. A cascade is a series of reactions in which one step activates the next in a sequence that results in an amplification of the response. An example of a cascade is shown below.

Figure 3.431 An example of a cascade, with one event leading to many more events

In the above example, A activates B, B activates C, D, and E, C activates F and G, D activates H and I, and E activates K and L. Cascades also help to serve as control points for certain process. In the protease cascade, the activation of B is really important because it starts the cascade.

The protease activation scheme starts with the enzyme enteropeptidase (secreted from the intestinal brush border) that converts trypsinogen (released by the pancreas) to trypsin. Trypsin can activate all the proteases (including itself) as shown in the 2 figures below.

Figure 3.432 Protease activation cascade

Figure 3.433 The protease activation cascade

The products of the action of the activated proteases on proteins are dipeptides, tripeptides, and individual amino acids, as shown below.

Figure 3.434 Products of pancreatic proteases

At the brush border, much like disaccharidases, there are peptidases that cleave some peptides down to amino acids. Not all peptides are cleaved to individual amino acid, because small

peptides can be taken up into the enterocyte, thus, the peptides do not need to be completely broken down to individual amino acids. Thus, the end products of protein digestion are primarily dipeptides and tripeptides, along with individual amino acids1.

Figure 3.435 Peptidases are produced by the brush border to cleave some peptides into amino acids

References & Links

1. Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.

Lipid Digestion in the Small Intestine

The small intestine is the major site for lipid digestion. There are specific enzymes for the digestion of triglycerides, phospholipids, and the removal of esters from cholesterol. We will look at each in this section. Refer back to sections 2.35, 2.36, and 2.36 for a review of these structures.

Triglycerides

The pancreas secretes pancreatic lipase into the duodenum as part of pancreatic juice. This major triglyceride digestion enzyme preferentially cleaves two fatty acids from triglycerides. This cleavage results in the formation of a monoglyceride and two free fatty acids as shown in Figures 3.441 & 3.442.

Figure 3.441 Pancreatic lipase cleaves the sn-1 and sn-3 fatty acids of triglycerides

Figure 3.442 The products of pancreatic lipase are a 2-monoglyceride and two free fatty acids

Phospholipids

The enzyme phospholipase A₂ cleaves the fatty acid of lecithin, producing lysolecithin and a free fatty acid. This is depicted in Figures 3.444 & 3.445.

Figure 3.444 Phospholipase A₂ cleaves the C-2 fatty acid of lecithin

Figure 3.445 Products of phospholipase A₂ cleavage

Cholesterol Esters

The fatty acid in cholesterol esters is cleaved by the enzyme, cholesterol esterase, producing cholesterol and a free fatty acid.

Figure 3.446 Cholesterol esterase cleaves fatty acids off of cholesterol

Figure 3.447 Products of cholesterol esterase

Formation of Mixed Micelles

If nothing else happened at this point, the monoglycerides and fatty acids produced by pancreatic lipase would form micelles. The hydrophilic heads would be outward and the fatty acids would be buried on the interior. These micelles are not sufficiently water-soluble to cross the unstirred water layer to get to the brush border of enterocytes. Thus, mixed micelles are formed containing cholesterol, bile acids, and lysolecithin in addition to the monoglycerides and fatty acids, as illustrated below1.

Figure 3.448 Normal (left) and mixed (right) micelles

Mixed micelles are more water-soluble, allowing them to cross the unstirred water layer to the brush border of enterocytes for absorption.

Figure 3.449 Mixed micelles can cross the unstirred water layer for absorption into the enterocytes

After digestion of carbohydrates, proteins, and fats is complete, the products below are ready for uptake into the enterocyte. This will be discussed in the next chapter.

Figure 3.55 Macronutrient digestion products ready for uptake into the enterocyte

References & Links

1. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

3.6 The Large Intestine

We have now reached a fork in the digestive road. We could follow the uptake of the digested compounds into the enterocyte or we could finish following what has escaped digestion and is going to continue into the large intestine. Obviously from the title of this section we are going to do the latter. As we learned previously, fiber is a crude term for what has survived digestion and has reached the large intestine.

Figure 3.61 The fork in the road between finishing digestion in the colon and absorption into the enterocyte

The ileocecal valve is the sphincter between the ileum (hence ileo- in ileocecal valve), and the large intestine. This name should make more sense as we go through the anatomy of the large intestine.

Figure 3.62 The ileocecal valve1

The large intestine consists of the colon, the rectum, and the anus. The colon can be further divided into the cecum (hence the -cecal in ileocecal valve), ascending colon, transverse colon, descending colon, and sigmoid colon as shown below.

Figure 3.63 Anatomy of the large intestine and rectum2

The large intestine is responsible for absorbing the remaining water and electrolytes (sodium, potassium, and chloride) in chyme. By removing water, the unabsorbed chyme is converted into a more solid form (feces) which is then excreted via defecation. The large intestine contains large amounts of microorganisms like those shown in the figure below.

Figure 3.64 Magnified image of bacteria3

The large intestine can also be referred to as the gut. There are a large number of microorganisms found throughout the gastrointestinal tract that collectively are referred to by a variety of names: flora, microflora, biota, or microbiota. Technically, microbiota is the preferred term because flora means "pertaining to plants". There are 10 times more microorganisms in the gastrointestinal tract than cells in the whole human body4. As can be seen in the figure below, the density of microorganisms increases as you move down the digestive tract.

Figure 3.65 Relative amounts of bacteria in selected locations of the GI tract. cfu/ml = colony forming unit, a measure of the number of live microorganisms in 1 mL of digestive sample5,6

As described in the fiber sections, there are two different fates for fiber once it reaches the large intestine. The fermentable, viscous fiber is fermented by bacteria. Fermentation is the metabolism of compounds by the microorganisms in the gut. An example of fermentation is the utilization of the oligosaccharides raffinose and stachyose by microorganisms that results in the production of gas, which can lead to flatulence. Additionally, some bile acids are fermented by microorganisms to form secondary bile acids that can be reabsorbed. These secondary bile acids represent approximately 20% of the total bile acids in our body. Fermentable fibers can also be used to form short-chain fatty acids that can then be absorbed and used by the body.

Conversely, the non-fermentable, non-viscous fiber is not really altered and will be a component of feces, that is then excreted through the rectum and anus via defecation. This process involves both an internal and external sphincter that are shown in figure 3.63 above.

References & Links

3.61 Probiotics & Prebiotics

Recently there has been increased attention given to the potential of a person's microbiota to impact health. This is because there are beneficial and non-beneficial bacteria inhabiting our gastrointestinal tracts. Thus, theoretically, if you can increase the beneficial, or decrease the non-beneficial bacteria, there may be improved health outcomes. In response to this, probiotics and prebiotics have been identified/developed. A probiotic is a live microorganism that is consumed, and colonizes in the body as shown in Figure 3.611.

Figure 3.611 Probiotics the consumption of the bacteria itself

A prebiotic is a non-digestible food component that selectively stimulates the growth of beneficial intestinal bacteria. An example of a prebiotic is inulin (this is not the same as, or related to, the hormone insulin that you may be familiar with), which is shown in the figure below.

Figure 3.612 Inulin, an indigestible food component that is a commonly used prebiotic The net result is the same for both prebiotics and probiotics, an improvement in the beneficial/non-beneficial bacteria ratio.

Figure 3.613 An effective prebiotic or probiotic should result in an increase in the beneficial bacteria

The following video does a nice job of explaining and illustrating how probiotics work. The NCCAM website is a good source of information if you have further questions on the topic.

Required Web Links Video: Probiotics (3:40) NCCAM: Probiotics

Some common examples of probiotic foods are sauerkraut, kimchi, kefir, and yogurts containing live cultures such as DanActive® and Activia®.

Required Web Links

DanActive® Activia®

It should be notes that the claims companies have made about their probiotic products have come under scrutiny. Dannon settled with the US Federal Trade Commission to drop claims that its probiotic products will help prevent colds or alleviate digestive problems, as seen in the top link below. General Mills also settled a lawsuit that accused them of a falsely advertising the digestive benefits of Yo-Plus, a product it no longer sells, as seen in the second link.

Required Web Link

New Campaign Markets Activia to Wider Audience General Mills Settles Yo-Plus Lawsuit

Some examples of prebiotics include the previously mentioned inulin, fructose-containing oligosaccharides and polysaccharides, and resistant starch. These are found in a number of foods including onions, leaks, sprouted whole grains, seeds, and berries.3

Resistant starch is so named because it is a starch that is resistant to digestion. As a result, it arrives in the colon to be fermented.

References & Links

Links

NCCAM: Probiotics - http://nccam.nih.gov/health/probiotics/ DanActive® - http://www.danactive.com/

Activia® - http://www.activia.us.com/

Danimals® - http://www.danimals.com/New Campaign Markets Activia to Wider Audience - http://www.nytimes.com/2014/01/06/business/media/new-campaign-markets-activia-to- wider-audience.html?_r=0

General Mills Settles Yo-Plus Lawsuit - http://www.foodbusinessnews.net/articles/news_home/Site_News/2013/02/General_Mills_se ttles_Yo-Plus.aspx?ID={40F62478-1AA4-49DF-9330-E41E19E946D0}&cck=1

Video

Probiotics - http://www.youtube.com/watch?v=2k8Puxz54FQ&NR=1

Chapter 4: Macronutrient Uptake, Absorption & Transport

The term absorption can have a number of different meanings. Not everything that is taken up into the enterocyte from the lumen of the GI tract will be absorbed, so the term uptake refers to compounds being transported into the enterocyte. Absorption means that a compound is transported from the enterocyte into the bloodstream for circulation throughout the body.

Under most circumstances, compounds that are taken up into the enterocytes will then be absorbed into the bloodstream. After this chapter, hopefully this distinction between these terms will be clear. After later micronutrient chapters, hopefully you will understand the reason for emphasizing this distinction.

Sections:

4.7 Glycemic Response, Insulin & Glucagon

Crypts of Lieberkuhn & Enterocyte Maturation

There are some additional anatomical and physiological features of the small intestine that are important to understand before defining uptake and absorption processes. Crypts of Lieberkuhn are pits located between the villi as pointed out by the green arrow in the figure below.

Figure 4.11 A crypt of Lieberkuhn is the pit between the villi in the small intestine as pointed out by the green arrow1

The crypts of Lieberkuhn (often referred to simply as crypts) are similar to the gastric pits in the stomach. The crypts contain stem cells at their bases that can produce a number of different cell types, including enterocytes2. From these stem cells, immature enterocyte cells are formed. As they mature, the enterocytes rise, or migrate up, the villi. Thus, the tips of villi are where the mature, fully functioning enterocytes are located, as represented by the purple cells in the figure below3.

Figure 4.12 Crypts are represented by green arrows, while fully mature enterocytes are represented by the purple cells at the top of the villi

This maturation and migration is a continuous process. The life cycle of an enterocyte is 72 hours once it enters the villus from the crypt2. At the top, enterocytes are sloughed off and, unless they are digested (they contain proteins and lipids) and components are taken up by enterocytes still on villi, they will be excreted in feces as depicted in the figure below.

Figure 4.13 Enterocytes sloughed off the villus. Unless these cells are digested and their components are taken up by other enterocytes on the villus, they will be excreted in feces.

Thus, we define absorption as reaching the bloodstream, because some compounds taken up into enterocytes will not always make it into the bloodstream. So remember, uptake is moving from the GI tract into the enterocyte, and absorption is moving from the enterocyte into the bloodstream.

References & Links

Uptake Lineup & Cell Membranes

Having completed digestion in the small intestine, a number of compounds are ready for uptake into the enterocyte. The figure below shows the macronutrient uptake lineup, or what is ready to be taken up into the enterocyte.

Figure 4.21 The macronutrient uptake lineup

From lipids, we have the lysolecithin (from phospholipid), 2-monoglyceride (from triglycerides), fatty acids, and cholesterol. From protein, there are small peptides (di- and tripeptides) and amino acids. From carbohydrates, only the monosaccharides glucose, galactose, and fructose will be taken up. The other macronutrient, water, has not been discussed so far because it does not undergo digestion.

In order to be taken up by the enterocytes, these compounds must now cross the cell (plasma) membrane, which is a phospholipid bilayer. In the cell membrane, the hydrophilic heads of the phospholipids point into the lumen of the GI tract, as well as towards the interior of the cell, while the hydrophobic tails are on the interior of the plasma membrane. This is depicted in the diagram below.

Figure 4.22 Plasma membrane of a cell

In addition to phospholipids, the cell membrane also contains proteins, cholesterol, and carbohydrates in addition to the phospholipids. Membrane proteins, such as channels, pumps, pores, and carriers are important for the transport of some compounds across the cell membrane. Figure 4.23 and two videos below do a nice job of illustrating the components of the cell membrane.

Figure 4.23 Cell membrane1

Required Web Links

Video: Cell Membrane (1:27)

Video: Voyage Inside the Cell: Membrane (1:23)

References & Links

1. http://en.wikipedia.org/wiki/File:Cell_membrane_detailed_diagram_4.svg

Videos

Cell Membrane - http://www.youtube.com/watch?v=owEgqrq51zY

Voyage Inside the Cell: Membrane - http://www.youtube.com/watch?v=GW0lqf4Fqpg

Transport Mechanisms Used for Uptake and Absorption

There are a number of different transport mechanisms utilized by your body for the uptake of nutrients into cells, and absorption into the bloodstream. These mechanisms can be classified as being either passive transport or active transport. The difference between the two types of transport is whether energy is required, and whether they move with or against a concentration gradient. Passive transport does not require energy and moves with a concentration gradient (high to low concentration). Active transport requires energy to move against the concentration gradient (low to high concentration).

A concentration gradient is a result of an unequal distribution of solutes within a solution. A solute is what is dissolved in a solvent in a solution. The more solute a region has, the higher the its concentration, while the less solute a region has, the lower the its concentration. Moving with the gradient is moving from a region of higher concentration to an area of lower concentration. Moving against the gradient is moving from an area of lower concentration to an area of higher concentration.

Figure 4.31 Movement with and against a concentration gradient.

Because our cells are surrounded by fluids containing varying amounts of solute, our body cells can experience concentration gradients across the plasma membrane. Hypertonic refers to a situation when the cell is surrounded by a solution that contains more solute than inside the cell. Hypotonic refers to a situation when the cell is surrounded by a solution containing less solutes than inside the cell. Isotonic refers to a situation when the cell is surrounded by a solution containing the same number of solutes that inside the cell. Figure 4.32 demonstrates these well.

Figure 4.32 Tonicity across the plasma membrane of cells.

The energy for active transport is provided by adenosine triphosphate (ATP), which is the energy currency in the body. Tri- means three, thus ATP is adenosine (composed of an adenine and a ribose) with three phosphate groups bonded to it, as shown below.

Figure 4.33 Structure of adenosine triphosphate (ATP)1

Phosphorylation is the formation of a phosphate bond. Dephosphorylation is the removal of a phosphate bond. Phosphorylation is an anabolic process that requires energy.

Dephosphorylation is a catabolic process that releases energy. Thus, energy is required to add phosphates to ATP, while energy is released through removing phosphates from ATP. Figure

Figure 4.34 The ATP Cycle demonstrating the processes of phosphorylation and dephosphorylation.

Subsections:

References & Links

1. https://userscontent2.emaze.com/images/92312f55-f2da-4d80-a1c3- 657851b8e450/bf6e4c6e-7a39-406f-aac7-b422321028a5.jpg

Passive Transport Mechanisms

There are three forms of passive transport involved in uptake and absorption of nutrients in the body:

Simple Diffusion

Simple diffusion is the movement of solutes from an area of higher concentration to an area of lower concentration (with the concentration gradient) without the help of a protein, as shown

in Figure 4.311.

Figure 4.311 Simple diffusion

Osmosis

Osmosis is similar to simple diffusion, but water moves instead of solutes. In osmosis water molecules move from an area of lower solute concentration to an area of higher solute concentration as shown below. The effect of this movement is to dilute the area of higher concentration.

Figure 4.312 Osmosis

The following videos do a nice job of illustrating osmosis.

Required Web Links

Video: Osmosis (0:47)

Video: Osmosis in the Kitchen (0:58)

Another example illustrating osmosis is the red blood cells in different solutions shown below.

Figure 4.313 Effect of salt solution concentration on red blood cells1

We will consider the simple example of salt as the solute. If the solution is hypertonic, that means that there is a greater concentration of salt outside (extracellular) the red blood cells than within them (intracellular). Water will then move out of the red blood cells to the area of higher salt concentration, resulting in the shriveled red blood cells depicted. Isotonic means that there is no difference between concentrations. There is an equal exchange of water between intracellular and extracellular fluids. Thus, the cells are normal, functioning red blood cells. A hypotonic solution contains a lower extracellular concentration of salt than the red blood cell intracellular fluid. As a result, water enters the red blood cells, possibly causing them to burst.

Facilitated Diffusion

The last form of passive transport is similar to diffusion in that it also moves with the concentration gradient (higher concentration to lower concentration). While it requires no energy, it does require a carrier protein to transport the solute across the membrane. Figure

4.314 and Required Video Link do a nice job of illustrating facilitated diffusion.

Figure 4.314 Facilitated diffusion examples2

Required Web Link

Video: Facilitated Diffusion (0:27)

References & Links

1. http://en.wikipedia.org/wiki/File:Osmotic_pressure_on_blood_cells_diagram.svg 2.https://en.wikipedia.org/wiki/Facilitated_diffusion#/media/File:Scheme_facilitated_diffusion

_in_cell_membrane-en.svg

Videos

Osmosis - http://www.youtube.com/watch?v=sdiJtDRJQEc

Osmosis in the Kitchen - http://www.youtube.com/watch?v=H6N1IiJTmnc&NR=1&feature=fvwp

Facilitated Diffusion - http://www.youtube.com/watch?v=s0p1ztrbXPY

Active Transport Mechanisms

There are two forms of active transport:

Active Carrier Transport

Active carrier transport (sometimes referred to as secondary active transport) is similar to facilitated diffusion in that it utilizes a protein carrier. However, energy is also required to move compounds against their concentration gradient (lower to higher concentration). Figure 4.321 and video do a nice job of illustrating active carrier transport.

Figure 4.321 Sodium-potassium ATPase (aka sodium-potassium pump) an example of active carrier transport1

Required Web Link

Video: Active Transport (0:21)

Endocytosis

Endocytosis is the engulfing of particles, or fluids, to be taken up into the cell. If a particle is endocytosed, this process is referred to as phagocytosis. If a fluid is endocytosed, this process is referred to as pinocytosis. Whenever a receptor located on the membrane is used to assist in engulfing an extracellular component, it is known as receptor mediated endocytosis. These processes are shown in Figure 4.322.

Figure 4.322 Different types of endocytosis2

The following video does a really nice job of showing how endocytosis occurs.

Required Web Link

Video: Endocytosis (0:35)

References & Links

Videos

Active Transport - http://www.youtube.com/watch?v=STzOiRqzzL4 Endocytosis - http://www.youtube.com/watch?v=4gLtk8Yc1Zc

Carbohydrate Uptake, Absorption, Transport & Liver Uptake

Monosaccharides (glucose, galactose, and fructose) are taken up into the enterocyte by two processes. Glucose and galactose are taken up by the sodium-glucose cotransporter 1 (SGLT1, active carrier transport). The cotransporter part of the name of this transporter means that it also transports sodium along with glucose or galactose. Fructose is taken up by facilitated diffusion through glucose transporter 5 (GLUT5). There are 12 glucose transporters that are named GLUT 1-12, and all use facilitated diffusion to transport various monosaccharides.

The different GLUTs have different functions and are expressed at high levels in different tissues. Thus, the intestine might be high in GLUT5, but not in GLUT12.

Once inside the enterocyte, all three monosaccharides are then transported out of the enterocyte and into capillaries or lacteals (absorption) through GLUT2 as shown in Figure 4.411.

Figure 4.41 Carbohydrate uptake and absorption

The capillaries and lacteals are located within each villus as shown below. Capillaries are the smallest blood vessels in the body, while lacteals are also small vessels but are part of the lymphatic system, as will be described further in a later subsection.

Figure 4.42 Anatomy of a villus2

The following video does a nice job of illustrating capillaries and lacteal and provides some basic detail on uptake into enterocytes and absorption into capillaries/lacteals.

Required Web Link

Video: Absorption in the Small Intestine

The capillaries in the small intestine join with the portal vein (a.k.a. hepatic portal vein), which transports monosaccharides directly to the liver. The figure below shows the portal vein and all the smaller vessels from the stomach, small intestine, and large intestine that feed into it.

Figure 4.43 The portal vein transports monosaccharides and amino acids to the liver3

In the liver, galactose and fructose are completely taken up by the hepatocytes, while only 30- 40% of glucose is taken up (more on this shortly.) The monosaccharides are phosphorylated by their respective kinase enzymes forming galactose-1-phosphate, fructose-1-phosphate, and glucose-6-phosphate as shown in Figure 4.44.

Figure 4.44 Hepatic monosaccharide uptake

Galactose-1-phosphate, fructose-1-phosphate, and glucose-6-phosphate are important for energy (ATP) production by cells as they can all enter glycolysis directly, or after undergoing conversion to another molecule. This will be covered in greater detail in Chapter 6.

References & Links

Video

Absorption in the Small Intestine - http://www.youtube.com/watch?v=P1sDOJM65Bc

Glycemic Response, Insulin, & Glucagon

If only 30-40% of glucose is being taken up by the liver, then what happens to the rest? How the body handles the rise in blood glucose after a meal is referred to as the glycemic response. The pancreas senses the blood glucose levels and responds appropriately. After a meal, the pancreatic beta-cells sense that glucose levels are high and secrete the hormone insulin, as shown in Figure 4.511.

Figure 4.51 Pancreatic beta-cells sense high blood glucose and secrete insulin

Thus, as can be seen in the following figure, blood insulin levels peak and drop with blood glucose levels over the course of a day.

Figure 4.52 Representative figure of blood glucose and insulin levels during a 24-hour period2

Blood glucose and insulin levels rise following carbohydrate consumption, and they drop after tissues have taken up the glucose from the blood (described below). Higher than normal blood sugar levels are referred to as hyperglycemia, while lower than normal blood sugar levels are known as hypoglycemia.

Insulin travels through the bloodstream to the muscle and adipose cells. There, insulin binds to the insulin receptor located within the cell membrane of the muscle and adipose cells. This causes GLUT4 transporters that are in vesicles inside the cell to move to the cell surface as shown below.

Figure 4.53 Response of muscle and adipose cells to insulin; 1) binding of insulin to its receptor,

The movement of the GLUT4 to the cell surface allows glucose to enter muscle cells and adipocytes (fat cells). The glucose is then phosphorylated to glucose-6-phosphate by hexokinase (different enzyme but same function as glucokinase in liver) to maintain gradient.

Figure 4.54 Response of muscle and adipose cells to insulin part 2; hexokinase phosphorylates glucose to glucose-6-phosphate

Glucagon is a hormone that has the opposite action of insulin. Glucagon is secreted from the

alpha-cells of the pancreas when they sense that blood glucose levels are low, as shown below.

Figure 4.55 Glucagon secretion from pancreatic alpha-cells in response to low blood glucose levels.

Glucagon binds to the glucagon receptors located in the cell membrane of hepatocytes, which causes the breakdown of the glycogen stored in the hepatocytes to glucose (glycogenolysis) as illustrated below.

Figure 4.56 Glucagon binding to its receptor leads to the breakdown of glycogen to glucose.

This glucose is then released into circulation which causes blood glucose levels to rise as shown below.

Figure 4.57 Glucagon leads to the release of glucose from the liver. Subsections:

References & Links

Diabetes

Diabetes is a condition of chronically high blood sugar levels. The prevalence of diabetes in the US has been rapidly increasing; the link below provides some statistics about prevalence.

Required Web Link

Diabetes Statistics

There are 2 forms of diabetes: Type 1 and Type 2.

In Type 1 diabetes, not enough insulin is produced, as shown in the figure below.

Figure 4.512 Type 1 diabetes

Without insulin, GLUT4 does not move to the surface of muscle and adipose cells, meaning glucose will not be taken up into these cells. This results in an increase in the amount of glucose remaining in circulation (i.e. increased blood sugar.)

Type 1 diabetes was previously known as juvenile-onset, or insulin-dependent diabetes and is estimated to account for 5-10% of diabetes cases1. Type 1 diabetics receive insulin through injections or pumps to manage their blood sugar.

In Type 2 diabetes, the body produces enough insulin, but the person's body is resistant to it. In Type 2 diabetics the binding of insulin to its receptor does not cause GLUT4 to move to the surface of the muscle and adipose cells as it normally should, thus no glucose will be taken up by these cells.

Figure 4.513 Type 2 diabetes

Type 2 diabetes accounts for 90-95% of diabetes cases, and was once known as non-insulin- dependent diabetes or adult-onset diabetes1. However, with the increasing rates of obesity, many younger people are being diagnosed with Type 2, making the adult-onset distinction no longer appropriate. Some people with Type 2 diabetes can control their condition with a diet and exercise regimen. This regimen improves their insulin sensitivity, or their response to the body’s own insulin. Others with Type 2 diabetes must receive insulin. These individuals are producing enough insulin, but are so resistant to it that more is needed for glucose to be taken up by their muscle and adipose cells.

The video below illustrates Type 2 diabetes.

Required Web Link

Video: Understanding Type 2 Diabetes (3:45)

References & Links

1. http://diabetes.niddk.nih.gov/dm/pubs/statistics/#what

Link

Diabetes Statistics - http://www.diabetes.org/diabetes-basics/statistics/

Video

Understanding Type 2 Diabetes - https://www.youtube.com/watch?v=JAjZv41iUJU

Glycemic Index

Research has indicated that hyperglycemia is associated with chronic diseases and obesity. As a result, measures of the glycemic response to food consumption have been developed so that people can choose foods with a smaller glycemic response. The first measure developed for this purpose was the glycemic index. The glycemic index is the relative change in blood glucose after consumption of 50 g of carbohydrate in a test food compared to 50 g of carbohydrates of a reference food (white bread or glucose). Thus, high glycemic index foods will produce a greater rise in blood glucose concentrations compared to low glycemic index foods, as shown in Figure 4.521.

Figure 4.521 Blood glucose response to a high glycemic index (GI) food compared to a low glycemic index food1

As a general guideline, a glycemic index that is 70 or greater is high, 56-69 is medium, and 55 and below is low. A stop light graphical presentation has been designed to emphasize the consumption of the low glycemic index foods while cautioning against the consumption of too many high glycemic index foods2.

Figure 4.522 Food glycemic index classifications2

The main problem with the glycemic index is that it does not take into account serving sizes. Let's take popcorn (glycemic index 89-127) as an example. A “serving size” of popcorn is 20 g, 11 g of which is carbohydrate3. This is equal to approximately 2.5 cups of popcorn4. Thus, a person would have to consume over 11 cups of popcorn to consume 50 g of carbohydrate needed for the glycemic index measurement. Another example is watermelon, which has a

glycemic index of 103, with a 120 g serving containing only 6 g of carbohydrates3. To consume the 50 g needed for glycemic index measurement, a person would need to consume over 1000 g (1 kg or 2.2 lbs.) of watermelon. Assuming this is all watermelon flesh (no rind), this would be over 6.5 cups of watermelon4.

The website glycemicindex.com (link provided below) contains a database you can search to see the glycemic index and glycemic load (covered in the next section) of various foods. The database also contains detail on how the measurement was done, and more information on the product itself. The top link below will take you to this website. The second link is to another database that contains the same information that might be easier for some people to use.

However, please note that in the second link the glycemic loads are calculated using 100 g serving sizes for all foods. This might not be the actual serving size for all foods, which is what is typically used, so it is important to keep this in mind.

Required Web Links

Glycemicindex.com

Glycemic Index & Glycemic Load of Foods

References & Links

Links

Glycemicindex.com - http://www.glycemicindex.com/

Glycemic Index & Glycemic Load of Foods - http://dietgrail.com/gid/

Glycemic Load

To incorporate serving size into the calculation, another measure known as the glycemic load

has been developed. It is calculated as shown below:

Thus, for most people, the glycemic load is a more meaningful measure of the glycemic impact of different foods. Considering the two previous examples from the glycemic index section, their glycemic loads would be:

Popcorn:

Glycemic load = (89-127 X 11 g)/100 = 9.79-13.97

Watermelon:

Glycemic load = (103 X 6 g)/100 = 6.18

As a general guideline for glycemic loads of foods: 20 or above is high, 11-19 is medium, and 10 or below is low1,2.

Figure 4.531 Food glycemic load classifications1,2

Putting it all together, popcorn and watermelon have high glycemic indexes, but medium and low glycemic loads, respectively.

You can also use the top two links below to find the glycemic loads of foods. However, please note that in the second link the glycemic loads are calculated using 100g serving sizes for all foods. This might not be the actual serving size for all foods, which is what is typically used, so it is important to keep this in mind. The third link is to the NutritionData estimated glycemic load tool that is pretty good at estimating the glycemic loads of foods, even if actual glycemic indexes have not been measured.

Required Web Links

Glycemicindex.com

Glycemic Index & Glycemic Load of Foods Estimated Glycemic Load

References & Links

Links

Glycemicindex.com - http://www.glycemicindex.com/

Glycemic Index & Glycemic Load of Foods - http://dietgrail.com/gid/

Estimated Glycemic Load - http://www.nutritiondata.com/help/estimated-glycemic-load

Protein Uptake, Absorption, Transport & Liver Uptake

There are a number of similarities between carbohydrate and protein uptake, absorption, transport, and uptake by the liver. Hopefully after this section you will understand these similarities.

Over 60% of all amino acids are taken up into the enterocyte as di- and tripeptides through the PepT1 transporter (active carrier transport). Individual amino acids are taken up through a variety of amino acid transporters. Once inside the enterocyte, peptidases cleave the peptides to individual amino acids. These cleaved amino acids, along with those that were taken up as individual amino acids, are moved into the capillary by another variety of amino acid transporters (some are the same as on the brush border, some are different).

Figure 4.61 Protein uptake and absorption

The capillary inside a villus is shown below.

Figure 4.62 Anatomy of a villus1

Like monosaccharides, amino acids are transported directly to the liver through the portal vein.

Figure 4.63 The portal vein transports monosaccharides and amino acids to the liver2

Amino acids are taken up into the hepatocyte through a variety of amino acid transporters. The amino acids can then be used to either make proteins, or are broken down to produce glucose, as will be described in Chapter 6.

Figure 4.64 Hepatic amino acid uptake

References & Links

Videos

Absorption in the Small Intestine - http://www.youtube.com/watch?v=P1sDOJM65Bc

Lipid Uptake, Absorption & Transport

Once mixed micelles reach the brush border of the enterocyte, two different lipid uptake mechanisms are believed to occur, but lipid uptake is not completely understood. One mechanism is that individual components of micelles may diffuse across the enterocyte. Otherwise, it is believed that some components may be taken up through unresolved transporters. For example, cholesterol transporters have been identified, but their overall mechanism of absorption is not well understood. The individual compounds are taken up as shown below.

Figure 4.71 Uptake of mixed micelle components into the enterocyte

Once inside the enterocyte, there are different fates for fatty acids, depending on their length. Short- and medium-chain fatty acids move through the enterocyte by simple diffusion and enter circulation through the capillaries; they are transported by the protein albumin. They will be carried to the liver by the portal vein, like monosaccharides and amino acids. Long-chain fatty acids, 2-monoglyceride, lysolecithin, and cholesterol will be re-esterified forming triglycerides, phosphatidylcholine, and cholesterol esters, respectively. These re-esterified lipids are then packaged into chylomicrons, which are lipoproteins, that are described in further detail in the next section. These chylomicrons are too large to fit through the pores in the capillaries, but they can fit through the larger fenestrations (openings) in the lacteal.

Figure 4.72 Fates of lipids in the enterocyte

Lacteals (shown below) are small vessels that feed into the lymphatic system. Thus, the chylomicrons enter the lacteals and enter into lymphatic circulation.

Figure 4.73 Anatomy of a villus, with the lacteal shown in blue1

The lymphatic system is a system similar to the circulatory system in that it contains vessels that transport fluid. However, instead of blood, the lymphatic system contains a clear fluid known as lymph. There are a number of lymph nodes (small glands) within the lymphatic system that play a key role in the body's immune system. The figure below shows the lymphatic system.

Figure 4.74 The lymphatic system2

The following videos describe and illustrate how the lymphatic system and lymph functions.

Required Web Links

Video: Lymphatic System (0:49) Video: Lymph Movement (0:44)

The lymphatic system enters general circulation through the thoracic duct that enters the left subclavian vein as shown below. In this case that means that it is not directed to the liver like other components that have been absorbed.

Figure 4.75 The thoracic duct is where the lymphatic system enters circulation. The animation below is an overview of lipid digestion, uptake, and initial transport.

Required Web Link

Animation: Lipid Digestion, Uptake, and Transport

Subsection:

References & Links

Link

http://www.wiley.com/college/grosvenor/0470197587/animations/Animation_Lipid_Digestion

_and_Absorption/Energy/media/content/dig/anima/dig5a/frameset.htm

Videos

Lymphatic system - http://www.youtube.com/watch?v=qTXTDqvPnRk Lymph Movement - https://www.youtube.com/watch?v=ZdYxx4CHb-A

4.71 Lipoproteins

Lipoproteins, as the name suggests, are complexes of lipids and protein. The proteins within a lipoprotein are called apolipoproteins (a.k.a. apoproteins). There are a number of different apolipoproteins that are abbreviated apo-, then an identifying letter (i.e. Apo A) as shown in the chylomicron below.

Figure 4.711 Chylomicron structure1

The following video does a nice job of illustrating the different lipoprotein components.

Required Web Link

Video: Lipoproteins (0:28)

There are a number of lipoproteins in the body. They differ by the apolipoproteins they contain,

size (diameter), density, and composition. Table 4.711 below shows the difference in density and diameter of different lipoproteins. Notice that as diameter decreases, density increases.

Table 4.711 The density and diameter of different lipoproteins2

This inverse relationship is a result of the larger lipoproteins being composed of a higher percentage of triglyceride and a lower percentage of protein as shown below.

Figure 4.712 Composition of lipoproteins3

Protein is denser than triglyceride (this is why muscle weighs more than fat). Thus, the higher the protein/lower triglyceride composition, the higher the density of the lipoprotein. Many of the lipoproteins are named based on their densities (i.e. very low-density lipoproteins).

As described in the last subsection, the lipoproteins released from the small intestine are chylomicrons. The video below does a nice job of showing, describing, and illustrating how chylomicrons are constructed and function.

Required Web Link

Video: Chylomicrons (0:55)

The endothelial cells that line blood vessels, especially in the muscle and adipose tissue, contain the enzyme lipoprotein lipase (LPL). LPL cleaves the fatty acids from lipoprotein triglycerides so that the fatty acids can be taken up into tissues. Figure 4.713 illustrates how endothelial cells are in contact with the blood that flows through the lumen of blood vessels.

Figure 4.713 Lining of a blood vessel. The lumen is where the blood would be flowing, thus endothelial cells are those that are in contact with blood4

LPL cleaves fatty acids from the triglycerides in the chylomicron, decreasing the amount of triglyceride in the lipoprotein. This lipoprotein with less triglycerides becomes what is known as a chylomicron remnant, as shown in Figure 4.714.

Figure 4.714 The cleavage of triglycerides by LPL from a chylomicron leads to the formation of a chylomicron remnant.

Now in the form of a chylomicron remnant, the digested lipid components originally packaged into the chylomicron are directed to the liver where the chylomicron remnant is pulled into the hepatocytes. This process of clearing chylomicrons from the blood takes 2-10 hours after a

meal2. This is why people must fast 12 hours before having their blood lipids (triglycerides, HDL, LDL, etc.) measured. This fast allows all the chylomicrons and chylomicron remnants to be cleared before blood is taken. However, whether patients should be asked to fast has been questioned as described in the link below.

Required Web Link

Should you fast before a cholesterol test?

After the chylomicron remnant has entered the hepatocytes, it is broken down to its individual components (triglycerides, cholesterol, protein etc.). In the liver, VLDL are produced, similar to how chylomicrons are produced in the small intestine. The individual components are packaged into VLDL and secreted into circulation as shown below.

Figure 4.715 Chylomicron remnants are taken up by the liver. The liver secretes VLDL that contain cholesterol (C)

Like it does to chylomicrons, LPL cleaves fatty acids from triglycerides in VLDL, forming the smaller IDL (aka VLDL remnant). Further action of LPL on IDL results in the formation of LDL. The C in Figures 4.715 and 4.716 represents cholesterol, which is not increasing; rather, since triglyceride is being removed, it constitutes a greater percentage of particle mass of lipoproteins. As a result, LDL is composed mostly of cholesterol, as depicted in Figure 4.716.

Figure 4.716 Formation of IDL and LDL from VLDL

LDL contains a specific apolipoprotein (Apo B100) that binds to LDL receptors on the surface of target tissues. The LDL are then endocytosed into the target tissue and broken down to cholesterol and amino acids.

HDL are made up of mostly protein and are derived from the liver and intestine. HDL participates in reverse cholesterol transport, which is the transport of cholesterol back to the liver. HDL picks up cholesterol from tissues/blood vessels and returns it to the liver itself or transfers it to other lipoproteins returning to the liver.

Figure 4.717 HDL is involved in reverse cholesterol transport

The animation under the transport button in the following link does a really nice job of going through the process of lipoprotein transport.

Required Web Link

Lipoprotein Animation

You are probably familiar with HDL and LDL being referred to as "good cholesterol" and "bad cholesterol," respectively. This is an oversimplification to help the public interpret their blood lipid values, because cholesterol is cholesterol; it's not good or bad. LDL and HDL are lipoproteins, and as a result you can't consume good or bad cholesterol, you consume cholesterol. A more appropriate descriptor for these lipoproteins would be HDL "good cholesterol transporter" and LDL "bad cholesterol transporter."

What's so bad about LDL?

LDL enters the endothelium where it is oxidized. This oxidized LDL is engulfed by white blood cells (macrophages), leading to the formation of what are known as foam cells. The foam cells eventually accumulate so much LDL that they die and accumulate, forming a fatty streak. From there, the fatty streak, which is the beginning stages of a lesion, can continue to grow until it blocks the artery. This can result in a myocardial infarction (heart attack) or a stroke. HDL is good in that it scavenges cholesterol from other lipoproteins or cells and returns it to the liver. The figure below shows the formation of the fatty streak and how this can progress to a point where it greatly alters blood flow.

Figure 4.718 The formation of a lesion in an artery5

The video below does an excellent job of illustrating this process. However, there are two caveats to point out. First, it incorrectly refers to cholesterol (LDL-C etc.), and second, it is clearly made by a drug company, so keep these factors in mind. The second link below is the American Heart Association’s simple animation of how atherosclerosis develops.

Required Web Links

Video: Atherosclerosis (5:36) Cholesterol and CAD

Despite what you learned above about HDL, a recent study questions its importance in preventing cardiovascular disease. It found that people who have genetic variations that lead to higher HDL levels were not at decreased risk of developing cardiovascular disease. You can read more about this interesting finding in the first link below. In addition, another recent study is questioning whether saturated fat is associated with an increased risk of cardiovascular disease.

Required Web Links

Doubt Cast on the ‘Good’ in ‘Good Cholesterol’

Study Questions Fat and Heart Disease Link

The following video gives a general overview of macronutrient digestion, uptake, and absorption.

Required Web Link

Video: Small Intestine (1:29)

References & Links

Links

Ask Well: Should you fast before a cholesterol test - http://well.blogs.nytimes.com/2016/05/24/ask-well-should-you-fast-before-a-cholesterol-test/ Lipoprotein Animation - http://www.wiley.com/legacy/college/boyer/0470003790/animations/cholesterol/cholesterol. swf

Cholesterol and CAD - http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=chlcad Doubt Cast on the ‘Good’ in ‘Good Cholesterol’ - http://www.nytimes.com/2012/05/17/health/research/hdl-good-cholesterol-found-not-to-cut- heart-risk.html

Study Questions Fat and Heart Disease Link - http://well.blogs.nytimes.com/2014/03/17/study- questions-fat-and-heart-disease-link/

Videos

Lipoproteins - https://www.youtube.com/watch?v=x-4ZQaiZry8 Chylomicrons - http://www.youtube.com/watch?v=hRx_i9npTDU LDL Receptor - http://www.youtube.com/watch?v=XPguYN7dcbE

Atherosclerosis - http://www.youtube.com/watch?v=fLonh7ZesKs&feature=rec-HM-r2 Small Intestine - http://www.youtube.com/watch?v=P1sDOJM65Bc

Chapter 5: Common Digestive Problems

When nutrients and energy are in short supply, cells, tissues, organs, and organ systems do not function properly. As a result, unbalanced diets can cause illness and disease. Conversely, certain illnesses and diseases can cause an inadequate uptake and absorption of nutrients, which in turn, simulates the health consequences of an unbalanced diet. Overeating high-fat foods and nutrient-poor foods can lead to obesity and exacerbate the symptoms of gastroesophageal reflux disease (GERD), gallstones, and irritable bowel syndrome (IBS). Many diseases and illnesses, such as celiac disease, interfere with the body getting its nutritional requirements. A host of other conditions and illnesses, such as peptic ulcers, Crohn’s disease, and ulcerative colitis, can also impair the process of digestion and/or negatively affect nutrient balance and decrease overall health. In this chapter, we will explore a variety of these digestive disorders.

Sections:

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a persistent form of acid reflux that occurs more than twice per week. Acid reflux occurs when the lower gastroesophageal sphincter (LES) to prevent the acidic contents of the stomach from leaking backward into the esophagus thus causing irritation.

Image Source: http://ddc.musc.edu/public/diseases/esophagus/gerd.html

Figure 5.11 The painful symptoms of GERD are caused by the leakage of acidic stomach contents into the esophagus.1

It is estimated that GERD affects 25 to 35 percent of the US population. An analysis of several studies published in the August 2005 issue of Annals of Internal Medicine concludes that GERD is much more prevalent in people who are obese2. While the links between obesity and GERD are not completely understood, the links likely include: a) excess body fat putting pressure on the stomach, b) overeating leading to high pressure inside the stomach, and/or c) increased consumption of fatty foods triggering GERD symptoms.

There are other causative factors of GERD as well. Sometimes the peristaltic contractions of the esophagus are sluggish and can compromise the clearance of acidic contents. In addition, some people with GERD are sensitive to particular foods—chocolate, garlic, spicy foods, fried foods, and tomato-based foods—which worsen symptoms. Drinks containing alcohol or caffeine may also worsen GERD symptoms.

GERD is diagnosed most often by a history of recurring symptoms. The most common symptom of GERD is heartburn but people with GERD may also experience regurgitation (flow of the

stomach’s acidic contents into the mouth), frequent coughing, nausea, wheezing, and trouble swallowing. A more proper diagnosis can be made when a doctor inserts a small device into the lower esophagus that measures the acidity of the contents during one’s daily activities.

Sometimes a doctor may use an endoscope, which is a long tube with a camera at the end, to view the tissue in the esophagus. About 50% of people with GERD have inflamed tissues in the

esophagus. Recurrent tissue damage can cause Barrett’s esophagus3. Barrett’s esophagus occurs in 5 to 15 percent of patients diagnosed with GERD and in some of these individuals, the condition may develop into cancer of the esophagus, a highly lethal cancer.

Normal Esophagus

Barrett’s Esophagus

Image Source: http://www.refluxcentar.com/en/oboljenja/barett-ov-jednjak/

Figure 5.12 Barrett’s esophagus occurs when the linings of the esophagus transform to tissue

types that are more consistent with the linings of the stomach or intestine.3

Approximately 35% of children born in the United States have GERD. In babies, the symptoms are more difficult to distinguish from what babies do normally. The symptoms are spitting up more than normal, incessant crying, refusal to eat, burping, and coughing. Most babies outgrow GERD before their first birthday but a small percentage do not.

The first approach to GERD treatment is dietary and lifestyle modifications. Suggestions are to reduce weight if you are overweight or obese, avoid foods that worsen GERD symptoms, eat smaller meals, stop smoking, and remain upright for at least three hours after a meal. There is some evidence that sleeping on a bed with the head raised at least six inches helps lessen the symptoms of GERD. People with GERD may not take in the nutrients they need because of the pain and discomfort associated with eating. As a result, GERD can cause an unbalanced diet and its symptoms can lead to a worsening of nutrient inadequacy, a vicious cycle that further compromises health. Many medications are available to treat GERD, including antacids (Maalox or Mylanta), histamine2 (H2) blockers (Tagamet, Zantac, Axid, and Pepcid), and proton-pump inhibitors (Prilosec, Prevacid, Nexium, and Aciphex. Evidence from several scientific studies indicates that medications used to treat GERD may accentuate certain nutrient deficiencies, namely zinc and magnesium4. When these treatment approaches do not work surgery is an

option. The most common surgical treatment involves reinforcing the lower esophageal sphincter, which serves as the barrier between the stomach and esophagus.

The following videos do a nice job of describing the causes, symptoms, and treatments of GERD.

Required Web Links

Video: Understanding GERD (3:04) Video: Gastric Reflux (GERD) (3:10)

References & Links

Videos

Understanding GERD - https://youtu.be/o8iShP84HP4

Gastric Reflux (GERD) - http://www.alilamedicalmedia.com/-/galleries/all-animations/digestive- system-videos/-/medias/d5d1ce1f-8214-4840-96dc-3f8a3c6b2491-gastric-reflux-gerd-narrated- animation

Peptic Ulcers

A peptic ulcer (stomach or duodenal) is a break in the inner lining of the esophagus, stomach, or duodenum. A peptic ulcer of the stomach is called a gastric ulcer, or duodenal ulcer when located in the duodenum, and esophageal ulcer when in the esophagus. Peptic ulcers occur when the lining of these organs is corroded by the acidic digestive (peptic) juices of the stomach. A peptic ulcer differs from an erosion because it extends deeper into the lining of the esophagus, stomach, or duodenum and incites more of an inflammatory reaction from the tissues that are involved. Chronic cases of peptic ulcers are referred to as peptic ulcer disease1.

Figure 5.21 A peptic ulcer in the duodenum1

Required Web Links

Video: Peptic Ulcers (5:34)

Video: Endoscopy of Two Giant Gastric Ulcers (0:27)

Peptic ulcer disease is common, affecting millions of Americans yearly. Moreover, peptic ulcers are a recurrent problem; even healed ulcers can recur unless treatment is directed at preventing their recurrence. The medical cost of treating peptic ulcer and its complications runs into billions of dollars annually. Recent medical advances have increased our understanding of ulcer formation. Improved and expanded treatment options now are available.

Symptoms of duodenal or stomach ulcer disease vary. Many people with ulcers experience minimal indigestion, abdominal discomfort that occurs after meals, or no discomfort at all. Some complain of upper abdominal burning or hunger pain one to three hours after meals or in the middle of the night. These symptoms are often promptly relieved by food or antacids that neutralize stomach acid. The pain of ulcer disease correlates poorly with the presence or severity of active ulceration. Some individuals have persistent pain even after an ulcer is almost completely healed by medication. Others experience no pain at all. Ulcers often come and go spontaneously without the individual ever knowing that they are present unless a serious complication (like bleeding or perforation) occurs2.

For many years, excess acid was believed to be the only cause of ulcer disease. Accordingly, the emphasis of treatment was on neutralizing and inhibiting the secretion of stomach acid. While

acid is still considered necessary for the formation of ulcers and its suppression is still the primary treatment, the two most important initiating causes of ulcers are infection of the stomach by a bacterium named Helicobacter pyloricus (H. pylori) and chronic use of nonsteroidal anti-inflammatory medications or NSAIDs, including aspirin. Cigarette smoking also is an important cause of ulcers as well as failure of ulcer treatment2.

Image Source: http://www.helico.com/images/o_helicobacter-pylori.png

Figure 5.22 Spiral-shaped H. pylori is the only bacteria known to colonize the human stomach3.

Required Web Links

Video: Tests for H. pylori (2:05)

Infection with H. pylori is very common, affecting more than a billion people worldwide. It is estimated that half of the United States population older than age 60 has been infected with H. pylori. Infection usually persists for many years, leading to ulcer disease in 10% to 15% of those infected. In the past, H. pylori was found in more than 80% of patients with gastric and duodenal ulcers. Diagnosis and treatment of this infection, the prevalence of infection with H. pylori, and the proportion of ulcers caused by the bacterium has decreased as the causes of peptic ulcers has been identified. It is estimated that currently only 20% of ulcers are associated with the bacterium. While the mechanism by which H. pylori causes ulcers is complex, elimination of the bacterium by antibiotics has clearly been shown to heal ulcers and prevent their recurrence3.

NSAIDs are medications used for the treatment of arthritis and other painful inflammatory conditions in the body1. Aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and etodolac (Lodine) are a few examples of this class of medications. NSAIDs cause ulcers by interfering with the production of prostaglandins in the stomach.

Cigarette smoking has been shown to not only cause ulcers, but it also increases the risk of complications from ulcers such as ulcer bleeding, stomach obstruction, and perforation.

Cigarette smoking is also a leading cause of failure of treatment for ulcers.

Contrary to popular belief, alcohol, coffee, colas, spicy foods, and caffeine have no proven role in ulcer formation. Similarly, there is no conclusive evidence to suggest that life stresses or personality types contribute to ulcer disease.

The goal of ulcer treatment is to relieve pain, heal the ulcer, and prevent complications. The first step in treatment involves the reduction of risk factors (NSAIDs and cigarettes). The next step is medications.

Antacids neutralize existing acid in the stomach. Histamine antagonists (H2 blockers) are drugs designed to block the action of histamine on gastric cells and reduce the production of acid.

While H2 blockers are effective in ulcer healing, they have a limited role in eradicating H. pylori without antibiotics. Therefore, ulcers frequently return when H2 blockers are stopped. Proton- pump inhibitors are more potent than H2 blockers in suppressing acid secretion. The different proton-pump inhibitors are very similar in action and there is no evidence that one is more effective than the other in healing ulcers. While proton-pump inhibitors are comparable to H2 blockers in effectiveness in treating gastric and duodenal ulcers, they are superior to H2 blockers in treating esophageal ulcers2.

References & Links

Videos

Gastric Ulcers - http://www.youtube.com/watch?v=98JaiKH2q3E Endoscopy of Two Giant Gastric Ulcers - http://www.youtube.com/watch?v=ncHcpzCnjGQ&feature=related Tests for H. pylori - https://youtu.be/9O98pscV9gQ

Gallstones

It is estimated that up to 1 million Americans are hospitalized annually as a result of gallstones, making it the most common of all digestive diseases1. Gallstones are formed when bile hardens in the gallbladder. 80% of gallstones are a result of cholesterol precipitation, while 20% are the

result of bile pigment precipitation2. The cause of gallstones is unknown2. The way in which gallstones are formed is shown in the following video.

Required Web Link

Video: Gallstones (0:27)

The following figure shows a severe case of gallstones.

Figure 5.31 Gallstones within a dissected gallbladder3

Many people do not experience symptoms from gallstones. They are usually discovered during examination for another health condition. However, some people experience an "attack" or pain that results from blockage of the bile ducts.

Prevention of gallstones is accomplished by maintaining a healthy weight and eating a diet high in fiber and low in simple carbohydrates. If there are no symptoms, treatment is usually not needed. In those who are having gallbladder attacks, surgery to remove the gallbladder, called a cholecystectomy, is typically recommended since the gallbladder is not considered an essential organ. After surgery, bile then flows directly from the liver into the small intestine. In those who are unable to have surgery, medication to try to dissolve the stones or shock wave lithotripsy may be tried3.

In the developed world, 10–15% of adults have gallstones. Rates in many parts of Africa, however, are as low as 3%. Gallbladder and biliary related diseases occurred in about 104 million people (1.6%) in 2013 and they resulted in 106,000 deaths. Women more commonly have stones than men and they occur more commonly after the age of 40. Certain ethnic groups have gallstones more often than others. For example, 48% of American Indians have gallstones. Once the gallbladder is removed, outcomes are generally good3.

References & Links

Video

Gallstones - http://www.youtube.com/watch?v=1q3NxfwSENM&feature=rec-HM-fresh+div

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is characterized by muscle spasms in the colon that result in abdominal pain, bloating, constipation, and/or diarrhea1. Interestingly, IBS produces no permanent structural damage to the large intestine as often happens to patients who have Crohn’s disease or other inflammatory bowel diseases. It is estimated that one in five Americans displays symptoms of IBS. The disorder is more prevalent in women than in men. Two primary factors that contribute to IBS are an unbalanced diet and stress.2

Symptoms of IBS significantly decrease a person’s quality of life, as they are present for at least twelve consecutive or nonconsecutive weeks in a year. Large meals and foods high in fat and added sugars, or those that contain wheat, rye, barley, peppermint, and chocolate intensify or bring about symptoms of IBS. Additionally, beverages containing caffeine or alcohol may worsen IBS. Stress and depression compound the severity and frequency of IBS symptoms.3

There is no specific test to diagnose IBS, but other conditions that have similar symptoms (such as celiac disease and peptic ulcers) must be ruled out. This involves stool tests, blood tests, and having a colonoscopy (which involves the insertion of a flexible tube with a tiny camera on the end through the anus so the doctor can see the colon tissues).3

There is no cure for IBS. As with GERD, the first treatment approaches for IBS are diet and lifestyle modifications. People with IBS are often told to keep a daily food journal to help identify and eliminate foods that cause the most problems. Other recommendations are to eat slower, add more fiber to the diet, drink more water, and to exercise. There are some medications (many of which can be purchased over-the-counter) to treat IBS and the resulting diarrhea or constipation. Sometimes antidepressants and drugs to relax the colon are prescribed.3

Required Web Link

Video: Irritable Bowel Syndrome (IBS) (4:16)

References & Links

Video

Irritable Bowel Syndrome - https://youtu.be/9f5wxYW0Z3k

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) refers to a number of inflammatory conditions in the intestine. The two most common are Crohn's disease and ulcerative colitis. These two conditions differ mainly in the areas of the intestine that are affected. Crohn's disease can occur anywhere throughout the GI tract, but most commonly occurs in the last part of the ileum.

Crohn's disease may also involve all layers of the intestine1. Ulcerative colitis are ulcers, or sores, in the lining of the colon and/or rectum2. It is estimated that up to 1 million people have IBD in the United States. Half of these individuals have Crohn's disease, and the other half have ulcerative colitis3.

Table 5.51 Differences between Crohn’s disease and Ulcerative colitis.4

Figure 5.51 Illustration of the differences between Crohn’s disease and ulcerative colitis.5

The exact causes of these two diseases is not known. One hypothesized cause for Crohn's disease is an overactive immune system that results in the chronic inflammation and collateral damage to the cells of the intestine, resulting in formation of lesions. The following videos do a nice job of illustrating the possible causes of Crohn’s disease and ulcerative colitis.

Required Web Link

Video: Pathology of Crohn’s disease (6:37) Video: Ulcerative Colitis (4:48)

Crohn's disease and ulcerative colitis present symptoms similar to other gastrointestinal diseases, such as irritable bowel syndrome and GERD.4 However, there are areas where the symptoms of the two do not overlap. Table 5.52 lists the typical symptoms of each.

Figure 5.52 Comparison of the symptoms of Crohn’s disease and ulcerative colitis.4

References & Links

Video

Pathology of Crohn’s disease - https://youtu.be/thzOJV-CHRo Ulcerative Colitis - https://youtu.be/dYQrqeTxC9g

Celiac Disease & Gluten

1 out of every 133 people in the United States has celiac disease1. People with celiac disease cannot consume the protein gluten because it causes their body to generate an autoimmune response (immune cells attack the body's own cells) that causes damage to the villi in the intestine, as shown in Figure 5.61.

Figure 5.61 Different stages of celiac disease2

This damage to the villi impairs the absorption of macronutrients and micronutrients from food.

There are a variety of symptoms for celiac disease that vary depending on age and from person to person. For a listing of all symptoms, see the first link below. The second link describes the difficulty in diagnosing this disease, which is reinforced by the third video link.

Required Web Link

What are the symptoms of celiac disease?

Celiac Disease, a Common, but Elusive, Diagnosis Video: Celiac's Disease (2:00)

The symptoms can appear in infancy or much later in life, even by age seventy. Celiac disease is not always diagnosed because the symptoms may be mild. A large number of people have what is referred to as “silent” or “latent” celiac disease. Figure 5.63 demonstrates how silent and latent conditions underlie the asymptomatic nature of the condition.3

Figure 5.63 Celiac Iceberg demonstrating the silent and latent phases that may exist prior to the development of symptoms.3

Villi destruction is what causes many of the symptoms of celiac disease. The destruction of the absorptive surface of the small intestine also results in the malabsorption of nutrients, so that while people with this disease may eat enough, nutrients do not make it to the bloodstream because absorption is reduced. The effects of nutrient malabsorption are most apparent in children and the elderly as they are especially susceptible to nutrient deficiencies. Over time, these nutrient deficiencies can cause health problems. Poor absorption of iron and folic acid can cause anemia, which is a decrease in red blood cells. Anemia impairs oxygen transport to all cells in the body. Calcium and vitamin D deficiencies can lead to osteoporosis, a disease in which bones become brittle.3

What is gluten?

Gluten is a protein that is bound to starch in the endosperm of grains such as:

Figure 5.62 Parts of a wheat granule4

Gluten-free diets have been increasing in popularity even for people who don’t have celiac disease. The thinking among those consuming these diets is that they might be gluten-sensitive, meaning that they experience adverse effects from consuming it. However, as the following videos describes, there is not much evidence to support people being gluten-sensitive.

Required Web Link

Video: Is Gluten-Sensitivity Real? (3:11)

Celiac disease is most common in people of European descent and is rare in people of African American, Japanese, and Chinese descent. It is much more prevalent in women and in people with Type 1 diabetes, autoimmune thyroid disease, and Down and Turner syndromes.

Symptoms can range from mild to severe and can include pale, fatty, loose stools, gastrointestinal upset, abdominal pain, weight loss and, in children, a failure to grow and thrive.3

References & Links

Links

What are the symptoms of celiac disease? - http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/#symptoms Celiac Disease, a Common, but Elusive, Diagnosis -

http://well.blogs.nytimes.com/2014/09/29/celiac-disease-diagnosis-gluten/

Videos

Celiac's Disease - http://www.nbcnews.com/nightly-news/video/celiac-disease-affecting- millions-of-americans-often-goes-undiagnosed-692131907739

Is Gluten-Sensitivity Real? - https://www.youtube.com/watch?v=EXON21V0v4o

Diverticulosis and Diverticulitis

Approximately 10% of people under 40, and 50% of people over 60 years old have a condition known as diverticulosis1. In this condition, diverticula (plural, diverticulum singular), or out- pouches, are formed at weak points in the large intestine, primarily in the lowest section of the sigmoid colon, as nicely shown in the figure below and in the video in the web link below.

Figure 5.71 Diverticula on the large intestine1

Required Web Link

Video: Diverticulosis (1:24)

It is believed that diverticula are formed as a result of a low-fiber diet because people may strain more during bowel movements. Most people with diverticulosis do not know that they have the condition. However, if the pouches become inflamed, then the condition is known as diverticulitis. Approximately 10 to 25 percent of people who have diverticulosis go on to develop diverticulitis.2 Symptoms include lower abdominal pain, nausea, and alternating between constipation and diarrhea.

The chances of developing diverticulosis and hence diverticulitis can be reduced with fiber intake because of what the breakdown products of the fiber do for the colon. The bacterial breakdown of fiber in the large intestine releases short-chain fatty acids. These molecules have been found to nourish colonic cells, inhibit colonic inflammation, and stimulate the immune system (thereby providing protection of the colon from harmful substances). Additionally, the bacterial indigestible fiber, mostly insoluble, increases stool bulk and softness increasing transit time in the large intestine and facilitating feces elimination. One uncomfortable side effect of consuming foods high in fiber is increased gas production since the byproducts of bacterial digestion of fiber are gases.

Several studies have found a link between high dietary-fiber intake and a decreased risk for colon cancer. However, an analysis of several studies published in the Journal of the American Medical Association in 2005 did not find that dietary-fiber intake was associated with a reduction in colon cancer risk3. There is some evidence that specific fiber types (such as inulin) may protect against colon cancer, but more studies are needed to conclusively determine how certain fiber types (and at what dose) inhibit colon cancer development.

The treatment the doctor prescribes will depend on how severe the condition is. Most cases of diverticulitis — about 75 percent of them — are uncomplicated. This means they have no other problems besides the actual inflammation or possible infection from the diverticulitis itself.

With uncomplicated diverticulitis, the doctor will likely suggest lots of rest and fluids during recovery from symptoms. They will also want to conduct follow-up assessments within a few days. In the meantime, the doctor may prescribe or recommend treatments such as medication, a liquid diet, or a low-fiber diet4.

References & Links

Video

http://www.youtube.com/watch?v=Mwa1qu9W2mM

Hemorrhoids

Hemorrhoids are swollen or inflamed veins of the anus or lower rectum. An internal hemorrhoid occurs within the anus, while an external hemorrhoid occurs in the skin surrounding the anus. Symptoms of hemorrhoids include bleeding, pain during bowel movements, and/or itching1. It is estimated that “about 75% of people will have hemorrhoids at some point in their lives”2.

Figure 5.81 Hemorrhoids3

The first 55 seconds of the following video does a nice job of illustrating what hemorrhoids are and how they develop.

Required Web Link

Video: Hemorrhoids (2:05)

The anus and lower rectum experience high pressure during bowel movements. Thus, hemorrhoids are believed to be caused by straining during bowel movements. To prevent this condition from occurring, it is recommended that people consume a high-fiber diet, drink plenty of water, and exercise to produce regular, large, soft stools. In addition, people should "go" at first urge and not wait until it is more than an urge2.

References & Links

Video

Hemorrhoids - http://www.youtube.com/watch?v=C8vZoIhQCwU

Chapter 6: Macronutrient & Alcohol Metabolism

Now that we have digested, taken up, absorbed, and transported the macronutrients, the next step is to learn how these macronutrients are metabolized. Alcohol is also included at the end of this chapter, even though it is not a macronutrient.

Sections:

6.1 Metabolism Basics

Metabolism consists of all the chemical processes that occur in living cells. These processes/reactions can generally be classified as either anabolic or catabolic. Anabolic means to build, catabolic means to breakdown. If you have trouble remembering the difference between the two, remember that anabolic steroids are what are used to build enormous muscle mass.

Figure 6.11 One of these two is taking anabolic steroids, which one would be your guess?

An anabolic reaction/pathway requires energy to build something. A catabolic reaction/pathway generates energy by breaking down something. This is shown in the example below of glucose and glycogen. The same is true for other macronutrients.

Figure 6.12 The breakdown of glycogen to glucose is catabolic. The glucose can then be used to produce energy. The synthesis of glycogen from glucose is anabolic and requires energy.

Anabolic and catabolic can also be used to describe conditions in the body. For instance, after a meal there is often a positive energy balance, or there is more energy and macronutrients than the body needs at that time. Thus, some energy needs to be stored and the macronutrients will be used for synthesis, such as amino acids being used for protein synthesis. However, after a fast, or a prolonged period without energy intake, the body is in negative energy balance and is considered catabolic. In this condition, macronutrients will be mobilized from their stores to be used to generate energy. For example, if prolonged enough, protein can be broken down, then the released amino acids can be broken down to be used as an energy source.

A number of the metabolic reactions either oxidize or reduce compounds. A compound that is being oxidized loses at least one electron, while a compound that is reduced gains at least one electron. To remember the difference, a mnemonic device such as OIL (oxidation is lost), RIG (reduction is gained) is helpful. Oxidation reactions and reduction reactions are “coupled” reactions, one cannot exist without the other. For example, a reduction reaction requires an electron. Where does that electron come from? It comes from an oxidation reaction. Scientists commonly refer to oxidation reactions and reduction reactions as oxidation-reduction reactions, or as redox reactions. Oxidation-reduction reactions are illustrated in the figure below.

Figure 6.13 The purple compound is being oxidized, the orange compound is being reduced1 Another way to remember oxidation versus reduction is LEO goes GER (like a lion)

Lose Elections = Oxidation

Gain Elections = Reduction (YES, gaining electrons is considered reduction)

Iron is a good example we can use to illustrate oxidation-reduction reactions. Iron commonly exists in two states (Fe3+ or Fe2+). It is constantly oxidized/reduced back and forth between the two states. The oxidation/reduction of iron is shown below.

Fe3+ loses an e- → Fe2+ (Oxidation) Fe2+ gains an e- → Fe3+ (Reduction)

Interestingly, the oxidation states of iron (mentioned above) are critical to our ability to use the iron present in our diet. Fe2+ (also known as ferrous iron) is easily absorbed in the small intestine. Fe3+ (also known as ferric iron) is not so easily absorbed. Gastric acid (produced by the stomach) and vitamin C promote the conversion of Fe3+ to Fe2+ so we can maximize iron absorption in the small intestine.

However, some oxidation reduction reactions are not as easy to recognize. There are some simple rules to help you recognize less-obvious oxidation/reduction reactions that are based upon the gain or loss of oxygen or hydrogen. These are as follows:

Oxidation: gains oxygen or loses hydrogen Reduction: loses oxygen or gains hydrogen

Remembering how this applies to hydrogen will be very helpful later in this chapter.

References

1. http://en.wikipedia.org/wiki/Image:Gulf_Offshore_Platform.jpg

6.11 Cofactors

A number of enzymes require cofactors to function. Cofactors can be either organic or inorganic molecules that are required by enzymes to function. Many organic cofactors are vitamins or molecules derived from vitamins. Most inorganic cofactors are minerals. Cofactors can be oxidized or reduced for the enzymes to catalyze the reactions.

Two common cofactors that are derived from the B vitamins, niacin and riboflavin, are NAD

(nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide), respectively.

Both of these cofactors can be reduced (remember that reduction is a process by which electrons, as part of H in this case, are gained); NAD is reduced to form NADH, while FAD is reduced to form FADH₂ as shown in the 2 figures below.

Figure 6.111 The reduction of NAD (left) to form NADH (right)3

Figure 6.112 The reduction of FAD (left) to FADH₂ (right) 4

NADH and FADH₂ are molecules that are critical to our cells’ ability to process the energized electrons obtained through the catabolism (digestion) of food molecules, like glucose. The energized electrons, which are highly reactive and potentially destructive, are temporarily managed by NADH and FADH₂ until they can be processed by the Electron Transport Chain step of Cellular Respiration (see Section 6.26 below).

An example of a mineral that serves as a cofactor is Fe2+ for proline and lysyl hydroxylases. Proline and lysine are two amino acids that must be hydroxylated (the addition of an OH group) in order to be used as building blocks for collagen, perhaps the most important structural protein in the body. We will discuss later in detail why vitamin C (ascorbic acid) is needed to reduce iron to Fe2+ so that it can serve as a cofactor for proline and lysyl hydroxylases.

Figure 6.115 Iron (Fe2+) is a cofactor for proline and lysyl hydroxylases

References & Links

Monosaccharide Metabolism

Galactose and fructose metabolism is a logical place to begin looking at carbohydrate metabolism, before shifting focus to the cell’s preferred monosaccharide, glucose. Once absorbed in the small intestine (Chapter 4), these monosaccharides are transported to the liver via the hepatic portal system. The figure below shows that galactose and fructose are phosphorylated (have a phosphate added to them) in the liver (a hepatocyte is a liver cell).

Figure 6.211 Uptake of monosaccharides into the hepatocyte

Galactose

As shown above, galactose is phosphorylated in the cells of the liver, resulting in a molecule called galactose-1-phosphate. Galactose -1-phosphate is converted to glucose-1-phosphate, before finally being converted to glucose-6-phosphate1. As shown below, glucose 6-phosphate can then be used in either glycolysis (the breakdown of glucose for energy) or glycogenesis (the production of glycogen for storage), depending on the person's current energy state.

Figure 6.212 Conversion of galactose-1-phosphate to glucose-6-phosphate

Fructose

Unlike galactose, fructose cannot be used to form glucose 6-phosphate. Instead, fructose-1- phosphate is cleaved in the liver to form glyceraldehyde 3-phosphate, an intermediate in the process of glycolysis (see Section 6.23 below).

The Importance of Glucose-6-Phosphate

Within hepatocytes or myocytes (muscle cells), glucose-6-phosphate can be used either for glycogenesis (glycogen synthesis) or glycolysis (breakdown of glucose for energy production). If the person is in an anabolic state (e.g. after a meal), they will use glucose-6-phosphate for storage. If they are in a catabolic state (e.g. fasted), they will use it for energy production.

Figure 6.214 The "fork in the road" for glucose-6-phosphate

References & Links

1. Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.

Glycogenesis & Glycogenolysis

As discussed earlier, glycogen is the stored form of glucose in humans. If a person is in an anabolic state, such as after consuming a meal, most glucose-6-phosphate within the myocytes (muscle cells) or hepatocytes (liver cells) is going to be stored as glycogen.

Glycogen is mainly stored in the liver and the muscle. It makes up ~6% of the weight of the liver, but only ~1% of muscle weight. However, since we have far more muscle mass in our body, there is 3-4 times more glycogen stored in muscle than in the liver2. This is of great practical importance since glycogen is an importance source of energy for muscle contraction. We have limited glycogen storage capacity in the liver. Thus, after a high-carbohydrate meal, our glycogen stores will reach capacity fairly quickly. After glycogen stores are filled, glucose will have to be metabolized in different ways for it to be stored in a different form, often as fat.

Glycogenesis

The synthesis of glycogen from glucose is a process known as glycogenesis. You will remember that glucose can be converted to glucose-6-phosphate (see Figure 6.211). If glucose storage (as glycogen) is required at any given time, the glucose-6-phosphate is converted to glucose-1- phosphate and then converted to glycogen (Figure 6.222).

Figure 6.222 Glycogenesis

Glycogenolysis

The process of liberating glucose from glycogen is known as glycogenolysis. This process is essentially the opposite of glycogenesis. Glycogen is hydrolyzed and the individual glucose molecules are phosphorylated (converted into glucose-6-phosphate) through the action of an

enzyme called glycogen phosphorylase as shown below3.

Figure 6.223 Glycogenolysis

References & Links

Glycolysis

If a person is in a catabolic state (in need of energy) such as during fasting, most glucose-6- phosphate will be used for glycolysis.

Figure 6.231 The "fork in the road" for glucose-6-phosphate

Glycolysis is the breaking down of one glucose molecule (6 carbons) into two pyruvate molecules (3 carbons). During the process, a net of two ATPs and two NADHs are also produced. The Figure 6.232 below shows the steps of glycolysis. Do not get overwhelmed, you will not have to learn every step. We will break it down into smaller sections and highlight the important intermediates, but I do want you to see how glucoses progresses through the various intermediate molecules before becoming pyruvate.

Figure 6.232 Glycolysis1

The following animation, using ball-and-stick models, allows you to control the 3 steps of glycolysis.

Required Web Links

Glycolysis Animation

3 steps of Glycolysis

Figure 6.233 Glycolysis step 1, energy investment1

Figure 6.234 Glycolysis step 2, glucose split1

Figure 6.235 Glycolysis step 3, energy harvesting1

Thus, from a molecule of glucose, the harvesting step produces a total of four ATPs and two NADHs. Remember that in Step 1 we had to “invest” two molecules of ATP to get the process started. Therefore, the net output from one molecule of glucose is two ATPs and two NADHs. You will remember that NADH is a molecule that is used to manage energized electrons. In this case, the splitting of the glucose molecule releases two energized electrons, which are then managed by two NADH molecules. These energized electrons will ultimately be processed by the Electron Transport Chain to generate ATP in the process of Cellular Respiration.

The figure below shows the stages of glycolysis, as well as the transition reaction, citric acid cycle, and electron transport chain that are utilized by cells to produce energy. They are also the focus of the next 3 sections. Again, you’re not going to have to memorize each step. This is just to give you an overview of the entire process.

Figure 6.236 Glycolysis, transition reaction, citric acid cycle, and the electron transport chain2

References & Links

Links

Glycolysis Animation - http://www.science.smith.edu/departments/Biology/Bio231/glycolysis.html

Transition Reaction

If a person is in a catabolic state, or needs energy, how the pyruvate molecules produced in glycolysis will be used depends on whether adequate oxygen levels are present. If oxygen levels are adequate (aerobic conditions), pyruvate moves from the cytoplasm, into the mitochondria, and then undergoes the transition reaction. If oxygen levels are not adequate (anaerobic conditions), pyruvate will remain in the cytoplasm to be used to produce lactate. We are going to focus on the aerobic pathway for now. We will address what happens under anaerobic conditions in the anaerobic respiration section.

Figure 6.241 Pyruvate fork in the road. What happens depends on whether it is aerobic or anaerobic respiration1

The transition reaction (sometimes called the transition step) is the transition between glycolysis and the citric acid cycle. It also represents a transition in location from the cytoplasm to the mitochondrion. The transition reaction converts pyruvate molecule (3 carbons) into acetyl CoA molecules (2 carbons), producing carbon dioxide (CO₂) and NADH as shown below. The figure below shows the transition reaction with CoA and NAD entering, and acetyl-CoA, CO₂, and NADH being produced.

Figure 6.242 Transition reaction2

The acetyl is combined with coenzyme A (CoA) to form acetyl-CoA. The structure of CoA is shown below. You can think of coenzyme A as an acetyl manager…a molecule that will deliver the 2-carbon acetyl group into the citric acid cycle (see Section 6.25).

In summary, the transition reaction converts each 3-carbon pyruvate into a 2-carbon acetyl group, which is then managed by coenzyme A. The transition reaction also generates CO₂ (a waste product), and NADH (a reduced molecule, contains energized electrons that will be processed by electron transport chain to make ATP).

References & Links

The Citric Acid Cycle

Acetyl-CoA is a central point in metabolism, meaning there are a number of ways that it can be used. We're going to continue to consider its use in an aerobic, catabolic state (need energy). Under these conditions, acetyl-CoA will enter the citric acid cycle (a.k.a. Krebs Cycle, TCA Cycle). The following figure shows the citric acid cycle. In the top left you will notice the acetyl-CoA we just produced.

Figure 6.251 The citric acid cycle1

The citric acid cycle begins by acetyl-CoA (2 carbons) combining with oxaloacetate (4 carbons) to form citrate (a.k.a. citric acid, 6 carbons). Coenzyme A is removed as part of this reaction leaving a single acetyl group to continue through the cycle. A series of transformations occur as the acetyl group is processed, creating a series of intermediates known as keto acids, until oxaloacetate if eventually reformed. During these intermediate steps, the acetyl group that was created during the formation of citrate is broken down and NADH, FADH₂, CO₂, and ATP are produced.

In summary, the Citric Acid Cycle processes each 2-carbon acetyl group from the transition reaction. The acetyl group is delivered by coenzyme A, and is progressively broken down, resulting in the production of carbon dioxide (a waste product), ATP, and NADH and FADH₂ (reduced molecules that contain energized electrons that will be processed by the Electron Transport Chain to make ATP).

The first video and the animation do a good job of explaining and illustrating how the cycle works. The second video is an entertaining rap about the cycle.

Required Web Links

Video: Citric acid cycle (0:44) Citric acid cycle animation

Video: TCA (Kreb's) Cycle Rap (3:01)

Through glycolysis, the transition reaction, and the citric acid cycle, multiple NADH and FADH₂ molecules are produced. Under aerobic conditions, these molecules will enter the electron transport chain to be used to generate energy through oxidative phosphorylation as described in the next section.

References & Links

Link

Citric Acid Cycle Animation - http://www.wiley.com/college/boyer/0470003790/animations/tca/tca.htm

Video

Citric acid cycle - http://www.youtube.com/watch?v=hw5nWB0xN0Y

TCA (Kreb's) Cycle Rap - http://www.youtube.com/watch?v=aMBIs_Iw0kE

Electron Transport Chain

The electron transport chain is located on the inner membrane of the mitochondria, as shown below.

Figure 6.261 The pathways involved in aerobic respiration1

The electron transport chain contains a number of electron carriers. These carriers take the electrons from NADH and FADH₂, pass them down the chain of complexes and electron carriers, and ultimately produce ATP. More specifically, the electron transport chain takes the energy from the electrons on NADH and FADH2 to pump protons (H+) into the intermembrane space.

This creates a proton gradient between the intermembrane space (high) and the matrix (low) of the mitochondria. The protons will then move back out through the enzyme ATP synthase from high to low concentration. This is similar to how a person rides up a motorized ski-lift (the proton pump) only to use gravity (high to low concentration) to come back down the hill. ATP synthase uses the energy of the moving protons to synthesize ATP (think of a hydroelectric dam using moving water to generate electricity.) Oxygen is required for this process because it serves as the final electron acceptor, forming water. Collectively this process is known as

oxidative phosphorylation. The following figure and animation do a nice job of illustrating how the electron transport chain functions.

Figure 6.262 Location of the electron transport chain in the mitochondria2

Required Web Link

ETC Animation

The electron transport chain generates 3 ATP for each NADH processed and 2 ATP for each FADH₂ processed. We can assess each of the catabolic steps of aerobic cellular respiration (steps that actually deconstruct the molecule of glucose) in terms of the number of NADH and FADH₂ molecules produced. For one molecule of glucose, the preceding pathways produce:

Glycolysis: 2 NADH Transition Reaction: 2 NADH

Citric Acid Cycle: 6 NADH, 2 FADH₂ Total 10 NADH, 2 FADH₂

Note: some textbooks will use 2.5/1.5 ATP for NADH/FADH₂ instead of the 3/2 we are using here. This is due to the fact that the actual total varies from organism to organism, and even

from one round to the next within the same organism. For simplicity’s sake, we will stick with 3/2 here.

In the following section (Section 6.27), we will compute exactly how many ATP can be generated from the aerobic breakdown of a single molecule of glucose.

The first video does a nice job of illustrating and reviewing the electron transport chain. The second video is a great rap video explaining the steps of glucose oxidation.

Required Web Links

Video: Electron Transport (1:43)

Video: Oxidate it or Love it/Electron to the Next One (3:23)

References & Links

Link

ETC Animation - http://www.science.smith.edu/departments/Biology/Bio231/etc.html

Videos

Electron Transport Chain - http://www.youtube.com/watch?v=1engJR_XWVU&feature=related Oxidate it or Love it/Electron to the Next One - http://www.youtube.com/watch?v=VCpNk92uswY&feature=response_watch

Aerobic Glucose Metabolism Totals

The table below shows the ATP generated from one molecule of glucose in the different metabolic pathways. As you look at Table 6.271 below, be sure to recognize that the ATP produced through Electron Transport is generated through the processing of the NADH and FADH₂ summarized in the previous section.

Notice that the vast majority of ATP is generated by the electron transport chain. Remember that this is an aerobic process and oxygen is the final electron acceptor. Oxygen is the key to the rich energy return of 38 ATP per molecule of glucose. If there were no oxygen, there would be no final electron acceptor. If there were no final electron acceptor, there would be no electron transport chain. If there were no electron transport chain, it would not be possible to process NADH and FADH₂. In the next section, we will see what happens if there is a limited supply of oxygen in our cells.

Table. 6.271 ATP generated from one molecule of glucose.

No References

Conditions without oxygen are referred to as anaerobic. In this case, the pyruvate will be converted to lactate in the cytoplasm of the cell as shown below.

Figure 6.281 Pyruvate fork in the road, what happens depends on whether it is aerobic or anaerobic respiration1

What happens if oxygen isn't available to serve as the final electron acceptor? As shown in the following video, the ETC becomes backed up with electrons and can't accept any more from NADH and FADH₂.

Web Link

Video: What happens when you run out of oxygen? (0:37)

This leads to a problem in glycolysis because NAD are limited and it is needed to accept electrons, as shown below. Without the electron transport chain functioning, once all NAD molecules have been reduced to NADH, glycolysis cannot continue to produce ATP from glucose.

Figure 6.282 Why NAD needs to be regenerated under anaerobic conditions2

Thus, there is a workaround to regenerate NAD by converting pyruvate (pyruvic acid) to lactate (lactic acid) as shown below.

Figure 6.283. The conversion of pyruvic acid to lactic acid regenerates NAD3,4

However, anaerobic respiration only produces 2 ATP from one molecule of glucose, compared to the 38 ATP from one molecule of glucose we saw with aerobic respiration. The biggest producers of lactate are muscle cells under oxygen stress (lacking adequate oxygen). During periods of intense activity, we might not be able to supply our muscle cells with sufficient oxygen to support the aerobic breakdown of glucose. At that point, our muscle cells are forced

to breakdown glucose in the absence of oxygen (which is essentially a process of glycolysis), which results in a limited amount of ATP and lactate (lactic acid). The lactate is generated because the conversion of pyruvate to lactate allows us to recycle NAD. The lactate produced, while technically a waste product, is still a metabolically valuable commodity. Through what is known as the Cori cycle, lactate produced in the muscle can be sent to the liver. In the liver, through a process known as gluconeogenesis, glucose can be regenerated and sent back to the muscle to be used again for anaerobic respiration forming a cycle as shown below.

Figure 6.284 The Cori cycle5

It is worth noting that the Cori cycle also functions during times of limited glucose (like fasting) to spare glucose by not completely oxidizing it.

References & Links

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Video

What happens when your run out of oxygen? - http://www.youtube.com/watch?v=StXlo1W3Gvg

6.3 Lipid Metabolism Pathways

Five lipid metabolic pathways/processes will be covered in the following subsections:

-Breakdown of triglycerides to glycerol and free fatty acids.

-Breakdown of fatty acids to acetyl-CoA

-Synthesis of fatty acids from acetyl-CoA and esterification into triglycerides

-Synthesis of ketone bodies from acetyl-CoA

6.31 Lipolysis (Triglyceride Breakdown)

Lipolysis is the cleavage of triglycerides to glycerol and fatty acids, as shown below.

Figure 6.311 Lipolysis

There are two primary lipolysis enzymes:

Despite performing the same function, the enzymes are primarily active for seemingly opposite reasons. In the anabolic state, LPL on the lining of blood vessels cleaves lipoprotein triglycerides into fatty acids so that they can be taken up into adipocytes (fat cells) for storage as triglycerides, or myocytes (muscle cells) where they are primarily used for energy production.

This action of LPL on lipoproteins is shown in Figures 6.312 & 6.313.

Figure 6.312 Lipoprotein lipase cleaves fatty acids from the chylomicron, forming a chylomicron remnant.

Figure 6.313 Lipoprotein lipase cleaves triglycerides from VLDL and IDL, forming subsequent lipoproteins (IDL and LDL) that contain less triglyceride

HSL is an important enzyme in adipose tissue, which is a major storage site of triglycerides in the body. HSL activity is increased by glucagon and epinephrine ("fight or flight" hormone), and decreased by insulin. Thus, during hypoglycemia (such as during a fast; a catabolic state), or a "fight or flight" response, triglycerides in the adipocytes (fat cells) are cleaved, releasing fatty acids into circulation that then bind with the transport protein albumin that carry them to muscle cells for use as an energy source. Thus, HSL is important for mobilizing fatty acids so they can be used to produce energy. The figure below shows how fatty acids can be taken up and used by tissues such as the muscle for energy production1.

Figure 6.314 Hormone-sensitive lipase

We are not going to focus on glycerol (the other product of triglyceride breakdown), but it does have two metabolic fates.

Figure 6.315 Metabolic fates of glycerol

References & Links

1. Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw's Perspectives in Nutrition. New York, NY: McGraw-Hill.

De novo Lipogenesis (Fatty Acid Synthesis)

De novo in Latin means "from the beginning." Thus, de novo lipogenesis is the synthesis of fatty acids, beginning with acetyl-CoA. You will remember that acetyl-CoA is the product of the transition reaction that is the starting point of the citric acid cycle. We had mentioned earlier

(in Section 6.25) that “Acetyl-CoA is a central point in metabolism.” Acetyl-CoA moves out of the mitochondria, where it is subsequently combined with additional acetyl-CoA molecules to form palmitate, a 16-carbon fatty acid1. The palmitate produced can be used as a component in the production of triglycerides (fat) for storage.

Figure 6.331 Fatty acid synthesis2

References

Ketone Body Synthesis

In cases where there is not enough glucose available for the brain (very low carbohydrate diets, starvation), the liver can use acetyl-CoA to synthesize ketone bodies (ketogenesis). The

structures of the three ketone bodies; acetone, acetoacetic acid, and beta-hydroxybutyric acid, are shown below.

Figure 6.341 The three ketone bodies, from top to bottom (acetone, acetoacetic acid, and beta- hydroxybutyric acid1)

After they are synthesized in the liver, ketone bodies are released into circulation where they can travel to the brain. The brain converts the ketone bodies to acetyl-CoA that can then enter the citric acid cycle for ATP production, as shown below.

Figure 6.342 The production, release, use, or exhalation of ketone bodies2

If there are high levels of ketones secreted, it results in a condition known as ketosis or ketoacidosis. The high level of ketones in the blood decreases the blood’s pH, meaning it becomes more acidic. It is debatable whether mild ketoacidosis (as seen with ketogenic and

Atkin’s diets) is harmful, but severe ketoacidosis can be lethal. One symptom of this condition is fruity or sweet-smelling breath, which is due to increased acetone exhalation.

References & Links

Cholesterol Synthesis

Acetyl-CoA is also used to synthesize cholesterol. As shown below, there are a large number of reactions and enzymes involved in cholesterol synthesis. You will not have to memorize all these steps, but it does illustrate the complexity of this process.

Figure 6.351 Cholesterol synthesis pathway1

Simplifying this, acetyl-CoA is converted to acetoacetyl-CoA (4 carbons) before forming 3- hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA is converted to mevalonate by the enzyme HMG-CoA reductase. This enzyme is important because it is the rate-limiting enzyme in cholesterol synthesis.

Figure 6.352 Cholesterol synthesis simplified2