Dietary amino acids can be consumed as free amino acids or, more often, they are acquired from digested dietary proteins that are hydrolyzed through the concerted actions of gastric and pancreatic peptidases. Dietary protein digestion begins in the stomach and continues within the lumen of the duodenum. Within the small intestines there are three principal pancreatic enzymes involved in protein digestion; these are pepsin, trypsin, and chymotrypsin. Several additional pancreatic peptidases play a lesser role in peptide digestion and include elastase and the carboxypeptidases.
The initial enzyme involved in protein digestion is gastric pepsins. Pepsins hydrolyze peptide bonds on the C-terminal side of aromatic and hydrophobic amino acids. Approximately 20% of overall protein digestion is accomplished via the actions of pepsins. Due to the acidic pH optimum for the action of pepsins, these enzymes are inhibited when the gastric juices (chyme) passes from the stomach and is mixed with alkaline pancreatic juices in the duodenum.
The remainder of protein digestion occurs within the duodenum and jejunum of the small intestine. Digestion here is primarily the result of the actions of trypsin and chymotrypsin, and to a lesser extent by elastase, and carboxypeptidases A and B, all of which are secreted by the pancreas. Active trypsin is generated via the action of enteropeptidase on pancreatic trypsinogen. Enteropeptidase is an enzyme secreted by cells of the crypts of Lieberkühn and resides in the brush-border membranes of duodenal mucosal cells. Trypsin then cleaves more trypsinogen to trypsin, as well as chymotrypsinogen, proelastase, and procarboxypeptidases to their active forms.
Following digestion, free amino acids, as well as peptides (2-6 amino acids in length) are absorbed by enterocytes of the proximal jejunum. Some absorption also occurs in the duodenum and a minor amount in the ileum. Although there is little nutritional significance to whole protein absorption, some undigested dietary protein does get absorbed by intestinal enterocytes. Of significance is the fact that endogenous proteins, such as intestinal hormones and peptides, are absorbed intact. This uptake occurs primarily within the large intestines.
The absorption of amino acids requires an active transport process that is dependent upon either Na+ or H+ co-transport. There are several amino acid transporters encompassing seven distinct transport systems which are further grouped into three broad categories. There are the neutral amino acid (monoamino monocarboxylic) transporters, the dibasic (and cysteine) amino acid transporters, and the acidic (dicarboxylic) amino acid transporters. All of these transporters are members of the solute carrier (SLC) family of transporters.
Intestinal uptake of peptides involves H+ co-transporters which are also members of the SLC family. The most abundant peptide transporter is PepT1 (SLC15A1) but there are three additional peptide transporters within the SLC15 subfamily. Within intestinal enterocytes the absorbed peptides are hydrolyzed to free amino acids via enterocyte cytoplasmic peptidases. The free amino acids are then transported across the apical membranes of enterocytes and enter the portal circulation.