Digestion of Dietary Proteins

DIGESTION OF DIETARY PROTEINS

Most of the nitrogen in the diet is consumed in the form of protein, typically amounting to 70–100 g/day in the American diet (see Figure 19.2). Proteins are generally too large to be absorbed by the intestine. [Note: An example of an exception to this rule is that newborns can take up maternal antibodies in breast milk.] They must, therefore, be hydrolyzed to yield di- and tripeptides as well as individual amino acids, which can be absorbed. Proteolytic enzymes responsible for degrading proteins are produced by three different organs: the stomach, the pancreas, and the small intestine (Figure 19.4).

Figure 19.4 Digestion of dietary proteins by the proteolytic enzymes of the gastrointestinal tract.

A. Digestion by gastric secretion

The digestion of proteins begins in the stomach, which secretes gastric juice, a unique solution containing hydrochloric acid and the proenzyme pepsinogen.

1. Hydrochloric acid: Stomach acid is too dilute (pH 2–3) to hydrolyze proteins. The acid, secreted by the parietal cells of the stomach, functions instead to kill some bacteria and to denature proteins, thereby making them more susceptible to subsequent hydrolysis by proteases.

2. Pepsin: This acid-stable endopeptidase is secreted by the chief cells of the stomach as an inactive zymogen (or proenzyme), pepsinogen. [Note: In general, zymogens contain extra amino acids in their sequences that prevent them from being catalytically active. Removal of these amino acids permits the proper folding required for an active enzyme.] Pepsinogen is activated to pepsin, either by hydrochloric acid or autocatalytically by pepsin molecules that have already been activated. Pepsin releases peptides and a few free amino acids from dietary proteins.

B. Digestion by pancreatic enzymes

On entering the small intestine, large polypeptides produced in the stomach by the action of pepsin are further cleaved to oligopeptides and amino acids by a group of pancreatic proteases that include both endopeptidases (cleave within) and exopeptidases (cut at an end). [Note: Bicarbonate (HCO₃^–), also secreted by the pancreas, raises the pH.]

1. Specificity: Each of these enzymes has a different specificity for the amino acid R-groups adjacent to the susceptible peptide bond (Figure 19.5). For example, trypsin cleaves only when the carbonyl group of the peptide bond is contributed by arginine or lysine. These enzymes, like pepsin described above, are synthesized and secreted as inactive zymogens.

Figure 19.5 Cleavage of dietary protein in the small intestine by pancreatic proteases. The peptide bonds susceptible to hydrolysis are shown for each of the five major pancreatic proteases. [Note: The first three are serine endopeptidases, whereas the last two are exopeptidases. Each is produced from an inactive zymogen.]

2. Release of zymogens: The release and activation of the pancreatic zymogens is mediated by the secretion of cholecystokinin and secretin, two polypeptide hormones of the digestive tract.

3. Activation of zymogens: Enteropeptidase (formerly called enterokinase), an enzyme synthesized by and present on the luminal surface of intestinal mucosal cells of the brush border membrane, converts the pancreatic zymogen trypsinogen to trypsin by removal of a hexapeptide from the N-terminus of trypsinogen. Trypsin subsequently converts other trypsinogen molecules to trypsin by cleaving a limited number of specific peptide bonds in the zymogen. Enteropeptidase, thus, unleashes a cascade of proteolytic activity because trypsin is the common activator of all the pancreatic zymogens (see Figure 19.5).

4. Abnormalities in protein digestion: In individuals with a deficiency in pancreatic secretion (for example, due to chronic pancreatitis, cystic fibrosis, or surgical removal of the pancreas), the digestion and absorption of fat and protein are incomplete. This results in the abnormal appearance of lipids in the feces (a condition called steatorrhea;) as well as undigested protein.

Celiac disease (celiac sprue) is a disease of malabsorption resulting from immune-mediated damage to the small intestine in response to ingestion of gluten (or gliadin produced from gluten), a protein found in wheat, barley and rye.

C. Digestion of oligopeptides by enzymes of the small intestine

The luminal surface of the intestine contains aminopeptidase, an exopeptidase that repeatedly cleaves the N-terminal residue from oligopeptides to produce even smaller peptides and free amino acids.

D. Absorption of amino acids and small peptides

Free amino acids are taken into the enterocytes by a sodium-linked secondary transport system of the apical membrane. Di- and tripeptides, however, are taken up by a proton-linked transport system. The peptides are hydrolyzed in the cytosol to amino acids that are released into the portal system by facilitated diffusion. Therefore, only free amino acids are found in the portal vein after a meal containing protein. These amino acids are either metabolized by the liver or released into the general circulation. [Note: Branched-chain amino acids are important examples of amino acids that are not metabolized by the liver but, instead, are sent from the liver primarily to muscle via the blood.]