Much of the body is made of protein, and these proteins take on a myriad of forms. They represent cell signaling receptors, signaling molecules, structural members, enzymes, intracellular trafficking components, extracellular matrix scaffolds, ion pumps, ion channels, oxygen and CO₂ transporters (hemoglobin). That is not even the complete list! There is protein in bones (collagen), muscles, and tendons; the hemoglobin that transports oxygen; and enzymes that catalyze all biochemical reactions. Protein is also used for growth and repair. Amid all these necessary functions, proteins also hold the potential to serve as a metabolic fuel source. Proteins are not stored for later use, so excess proteins must be converted into glucose or triglycerides, and used to supply energy or build energy reserves. Although the body can synthesize proteins from amino acids, food is an important source of those amino acids, especially because humans cannot synthesize all of the 20 amino acids used to build proteins.

The digestion of proteins begins in the stomach. When protein-rich foods enter the stomach, they are greeted by a mixture of the enzyme pepsin and hydrochloric acid (HCl; 0.5 percent). The latter produces an environmental pH of 1.5–3.5 that denatures proteins within food. Pepsin cuts proteins into smaller polypeptides and their constituent amino acids. When the food-gastric juice mixture (chyme) enters the small intestine, the pancreas releases sodium bicarbonate to neutralize the HCl. This helps to protect the lining of the intestine. The small intestine also releases digestive hormones, including secretin and CCK, which stimulate digestive processes to break down the proteins further. Secretin also stimulates the pancreas to release sodium bicarbonate. The pancreas releases most of the digestive enzymes, including the proteases trypsin, chymotrypsin, carboxypeptidase, and elastase, which aid protein digestion. Together, all of these enzymes break complex proteins into smaller individual amino acids (Figure 24.4.1), which are then transported across the intestinal mucosa to be used to create new proteins, or to be converted into fats or acetyl CoA and used in the Krebs cycle.

In order to avoid breaking down the proteins that make up the pancreas and small intestine, pancreatic enzymes are released as inactive proenzymes that are only activated in the small intestine. In the pancreas, vesicles store trypsin, chymotrypsin, and carboxypeptidase as trypsinogen, chymotrypsinogen, and procarboxypeptidase. Once released into the small intestine, an enzyme found in the wall of the small intestine, called enterokinase, binds to trypsinogen and converts it into its active form, trypsin. Trypsin then binds to chymotrypsinogen and procarboxypeptidase to convert it into the active chymotrypsin and carboxypeptidase. Trypsin, chymotrypsin, and carboxypeptidase break down large proteins into smaller peptides, a process called proteolysis. These smaller peptides are catabolized into their constituent amino acids by the brush border enzymes, aminopeptidase and dipeptidase. The free amino acids are then transported across the apical surface of the intestinal mucosa in a process that is mediated by secondary active transport using sodium-amino acid transporters. These transporters bind sodium and then bind the amino acid to transport it across the membrane. At the basal surface of the mucosal cells, the sodium and amino acid are released. The sodium can be reused in the transporter, whereas the amino acids are transferred into the bloodstream to be transported to the liver and cells throughout the body for protein synthesis.

Freely available amino acids are used to create proteins. If amino acids exist in excess, the body has no capacity or mechanism for their storage; thus, they are converted into glucose or ketones, or they are decomposed. Amino acid decomposition results in hydrocarbons and nitrogenous waste. However, high concentrations of nitrogen are toxic as they produce ammonium ions. The urea cycle processes nitrogen and facilitates its excretion from the body.

Urea Cycle

The urea cycle is a set of biochemical reactions that produces urea from ammonium ions in order to prevent a toxic level of ammonium in the body. It occurs primarily in the liver and, to a lesser extent, in the kidney. Prior to the urea cycle, ammonium ions are produced from the breakdown of amino acids. In these reactions, an amine group, or ammonium ion, from the amino acid is exchanged with a keto group on another molecule. This transamination event creates a molecule that is necessary for the Krebs cycle and an ammonium ion that enters into the urea cycle to be eliminated.

In the urea cycle, ammonium is combined with CO₂, resulting in urea and water. The urea is eliminated through the kidneys in the urine (Figure 24.4.2).

Amino acids can also be used as a source of energy, especially in times of starvation. Because the processing of amino acids results in the creation of metabolic intermediates, including pyruvate, acetyl CoA, acetoacyl CoA, oxaloacetate, and α-ketoglutarate, amino acids can serve as a source of energy production through the Krebs cycle (Figure 24.4.3). Figure 24.4.4 summarizes the pathways of catabolism and anabolism for carbohydrates, lipids, and proteins.