Dietary Protein Digestion by pancreatic enzymes

On entering the small intestine, the 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 (that cleave within) and exopeptidases (that cut at an end). [Note: Bicarbonate  (HCO₃⁻), secreted by the pancreas in response to the intestinal hormone secretin, raises the intestinal pH.]

1. Specificity: Each of these enzymes has a different specificity for the amino acid R-groups adjacent to the susceptible peptide bond (Fig. 1). 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 1:  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. Zymogen release: The release and activation of the pancreatic zymogens are mediated by the secretion of cholecystokinin, a polypeptide hormone of the small intestine).

3. Zymogen activation: Enteropeptidase (also called enterokinase), a serine protease synthesized by and present on the luminal (apical)  surface of intestinal mucosal cells (enterocytes) of the brush border,  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. Thus, enteropeptidase unleashes a cascade of proteolytic activity because trypsin is the common activator of all the pancreatic zymogens (see Fig. 1).

4. Digestion abnormalities: In individuals with a deficiency in pancreatic secretion (for example, because of 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.