8.1 Intraluminal Digestion

Digestion of protein begins in the stomach under the influence of pepsin. This lasts for only one to two hours, while the pH is acidic following meal-stimulated acid secretion. Most dietary protein, however, is hydrolyzed by pancreatic proteases secreted into the proximal duodenum in inactive form. Activation of each protease is initially catalyzed by the duodenal mucosal surface enzyme enterokinase and by activated trypsin (Figure 13). Activation is virtually instantaneous in the first and second portions of the duodenal lumen. Intraluminal digestion of dietary protein occurs in the duodenum by sequential action of pancreatic endopeptidases and exopeptidases. The endopeptidases trypsin, chymotrypsin, elastase, DNAase and RNAase act on the peptide at the interior of the protein molecule. These peptides are then acted upon by the exopeptidases carboxypeptidase A and B, which remove a single amino acid from the carboxyl terminal end of the peptide, yielding basic and neutral amino acids (AAs) as well as small peptides.

Peptidases in the brush border then hydrolyze the residual di-, tri- and tetrapeptides that contain neutral AAs. Peptides consisting primarily of glycine, proline, hydroxyproline or dicarboxylic AA appear to be hydrolyzed inside the cell. AA and dipeptides are then transported into the mucosal cell interior. The transport system for neutral AA absorbs aromatic (phenylalanine, tyrosine, tryptophan) and aliphatic (valine, leucine, isoleucine, methionine) AAs. The basic AAs (arginine, lysine) are absorbed by a separate mechanism. There is a third mechanism for glycine, proline and hydroxyproline, and a fourth for dicarboxylic AAs (aspartic and glutamic AA).

From these physiological considerations, protein malabsorption would be expected in diseases causing (1) pancreatic insufficiency; (2) generalized impaired enterocyte function - e.g., celiac disease; and (3) loss of mucosal surface - e.g., the short bowel syndrome.