Proteins can be broken down into long peptides by the acidic pH in the stomach. However, in order for the body to absorb proteins, three phases of enzymatic digestion are necessary. The first phase occurs in the stomach and is mediated by pepsin, which is produced by the chief cells in the gastric glands. When gastric secretion is triggered by signals associated with eating, pepsinogen is released and converted to the active enzyme, pepsin, in the presence of low pH. Pepsin specifically cleaves proteins at sites containing neutral amino acids, preferably those with aromatic or large aliphatic side chains. However, since these amino acids are not found frequently in a given protein, pepsin cannot fully digest proteins into a form that can be absorbed by the intestine. Instead, it produces a mixture of intact proteins, large peptides, and a limited number of free amino acids.

When the partially digested protein enters the small intestine, it encounters proteases in pancreatic juice. These enzymes are initially secreted in inactive forms. Activation of these proteases occurs in the lumen of the small intestine due to the presence of an activating enzyme called enterokinase, located on the brush border of small intestinal epithelial cells. Enterokinase cleaves trypsinogen to yield active trypsin. Trypsin, in turn, activates other protease precursors secreted by the pancreas, resulting in a mixture of enzymes that can effectively digest the majority of dietary proteins. Trypsin is an endopeptidase that cleaves proteins at internal bonds within the peptide chain, rather than releasing individual amino acids from the ends of the chain. It specifically cleaves at basic amino acids, leading to the formation of shorter peptides with a basic amino acid at their C-terminus. The other pancreatic endopeptidases, chymotrypsin and elastase, have a similar mode of action but cleave at sites containing neutral amino acids.
•Fig. 30.10 Naturallyoccurringdietaryaminoacids.Thoseinboxesareessentialaminoacidsthatcannotbesynthesizedbyhumansandthusmustbeobtainedfromthediet.(RedrawnfromBarrettKE.Gastrointestinal Physiology. NewYork:McGraw-Hill;2006.)Amino acids NeutralBasicArg HisLys AcidicGlu, Gln Asp, Asn AllphaticGly, Ala AromaticTyr Phe Try HydroxylSer Thr SulfurCys Met IminoPro HydroxyproLeu lleVal , , , ,
Digestion of Proteins
Proteins can be hydrolyzed to long peptides simply by virtue of the acidic pH that exists in the gastric lumen. However, for assimilation of proteins into the body, three phases of enzymatically mediated digestion are required (
Fig. 30.11 ). Like acid hydrolysis, the first of these phases takes place in the gastric lumen and is mediated by pepsin, the product of chief cells localized to the gastric glands. When gastric secretion is activated by signals coincident with ingestion of a meal, pepsin is released from the chief cells as the inactive precursor pepsinogen. At acidic pH, this precursor is autocatalytically cleaved to yield the active enzyme. Pepsin is highly specialized to act in the stomach, since it is activated by low pH. The enzyme cleaves proteins at sites of neutral amino acids, with a preference for aromatic or large aliphatic side chains. Because such amino acids occur only relatively infrequently in a given protein, pepsin is not capable of digesting protein fully into a form that can be absorbed by the intestine. Instead it yields a mixture of intact protein, large peptides (the majority), and a limited number of free amino acids.
On moving into the small intestine, the partially digested protein encounters the proteases provided in pancreatic juice. Recall that these enzymes are secreted in inactive forms. How then are they activated to begin the process of protein digestion? In fact, activation of proteases is delayed until these enzymes are in the lumen by virtue of the localized presence of an activating enzyme, enterokinase, only on the brush border of small intestinal epithelial cells (
Fig. 30.12 ). Enterokinase cleaves trypsinogen to yield active trypsin. Trypsin in turn cleaves all the other protease precursors secreted by the pancreas, thereby resulting in a mixture of enzymes that can almost completely digest the vast majority of dietary proteins. Trypsin is an endopeptidase that cleaves proteins only at internal bonds within the peptide chain rather than releasing individual amino acids from the end of the chain. Trypsin is specific for cleavage at basic amino acids, and such cleavage results in a set of shorter peptides with a basic amino acid at their C-terminus. The two other pancreatic endopeptidases, chymotrypsin and elastase, have a similar mechanism of action but cleave at sites of neutral •Fig. 30.11 Hierarchyofproteasesandpeptidasesthatfunctioninthestomachandsmallintestinetodigestdietaryprotein.Proteinsareabsorbedaseithersingleaminoacids(70%)orshortpeptides(30%).(AdaptedfromVanDykeRW.In:SleisengerMH,FordtranJS[eds].Gastrointestinal Disease. 4thed.
Philadelphia:Saunders;1989.) •Fig. 30.12 Conversionoftheinactiveproenzymesofpancreaticjuicetoactiveenzymesbytheactionoftrypsin.Trypsinogeninpancre-aticjuiceisproteolyticallyconvertedtoactivetrypsinbyenterokinaseexpressedonthesurfaceofepithelialcellsoftheduodenumandjejunum.Trypsinthenactivatestheotherproenzymesasshown.