Two organs have particular, potentially important, regulatory roles during feeding: the gut and liver. All dietary intake passes first through the gut and then through the liver via portal blood flow. Digestion of protein begins with pepsin secretion in gastric juice and with proteolytic enzymes secreted from the pancreas and the mucosa of the small intestine (133). These enzymes are secreted in their "pro" (or zymogen) form and become activated by cleavage of a small peptide portion. Pancreatic proenzymes become activated by intestinal enterokinase secreted into the intestinal juice to cleave trypsinogen to trypsin. The presence of dietary protein in the gut appears to signal secretion of the enzymes. As trypsin becomes activated, it binds to proteins to initiate hydrolysis. An excess of trypsin occurs when either more trypsin is secreted than there is protein present or when most of the dietary protein has been hydrolyzed. At this point the presence of unbound trypsin appears to signal a feedback regulation system to the pancreatic acinar cells to inhibit synthesis and secretion of trypsinogen. Some plants, such as soybeans, contain protein inhibitors of proteolytic enzymes such as trypsin. These proteins may often be denatured by heating (i.e., by cooking). Feeding unheated soybeans to rats results in hypertrophy of the pancreas, presumably caused by hypersecretion of pancreatic juices. The presumed mechanism is that the trypsin inhibitor in soy binds trypsin, which, in the free state, serves as a feedback inhibitor of pancreatic secretion ( 134).
The events of protein digestion and absorption as shown in Figure..2..17 are well established (133, 13.5., 136, 137 and 138). Proteins are successively broken down into smaller peptides on the basis of the amino acid residues targeted by the proteolytic enzymes. For example, pepsin has a relatively low specificity for neutral amino acids such as leucine or phenylalanine, whereas trypsin shows specificity for a basic target (lysine or arginine). In addition, exopeptidases attack the free ends of the peptide chains: pancreatic carboxypeptidases at the carboxyl terminus, and aminopeptidases secreted in intestinal juice at the amino terminus.
Figure 2.17. Digestion and absorption of dietary protein in the intestine. The secretion and feedback system of the pancreatic trypsinogen/trypsin is shown. In addition to the assumed dietary protein load of 100 g, an additional protein load of about 70 g occurs from secretion of protein and sloughing of mucosal cells. Under normal conditions, almost all of the protein is recovered by hydrolysis and absorption. Amino acids are absorbed by active transport through the mucosal cells into the portal blood system. Some amino acids are immediately metabolized by gut and liver during absorption. (From Crim MC, Munro HN. Protein and amino acid requirements and metabolism in relation to defined formula diets. In: Shils ME, ed. Defined formula diets for medical purposes. Chicago: American Medical Association, 1977;5-15, with permission.)
The free amino acids are absorbed by active transport into the mucosa by transporters specific to different types of amino acids ( 136, 137). At the same time, peptides, in particular di- and tripeptides, are assimilated on the luminal side intact. Peptide hydrolases present in the brush border and cytosol of the mucosal cells complete the hydrolysis of these peptides prior to their release into the portal blood system. There are specific transport systems for peptide uptake into mucosal cells, separate from the transporters for amino acids. It is thought that a quarter of dietary protein is absorbed as di- and tripeptides ( 139). For example, patients with the rare genetic Hartnup disease with a defect in renal and gut transport of selected amino acids cannot transport free tryptophan into mucosal cells but do indeed absorb tryptophan when it is administered as a dipeptide (140, 141).
Fi.gure2,17 shows that in addition to dietary protein, protein is added directly to the lumen in the form of secreted proteins and sloughed cells. Because the small intestine is continually being remodeled with cells formed in the crypts migrating toward the villus tips, epithelial and other cells are continuously being sloughed off the tips of the villi. Although the exact amounts of protein secreted and cells sloughed are unknown, a reasonable estimate is that of the 70 g of protein added to the lumen, 20 g may come from secreted proteins and 50 g may come from sloughed cells (135). As indicated in Flg.yie,.2.:17, most of this protein is efficiently reabsorbed.
To a limited but important extent, some proteins and large peptides enter intact directly from the gut into the basolateral blood. Absorption of intact proteins or large portions of proteins is a tenable physiologic explanation for numerous diseases involving food allergies and idiosyncrasies. The gut is generally viewed as an impermeable barrier that nutrients cross by active transport or where a break in the barrier occurs through cell injury. Small amounts of some proteins may pass this barrier by several possible mechanisms, such as through "leaks" between epithelial cell junctions or possibly by transport through uptake into vesicles from the lumen to the submucosal side of the epithelial cells (142). Again, the amount of protein entering intact is small, but it may be important in situations of immune response to the proteins or in delivery of some peptide drugs.
Was this article helpful?