Evidence for two different modes of tripeptide disappearance in human intestine. Uptake by peptide carrier systems and hydrolysis by peptide hydrolases

Abstract

The intestinal fate of two tripeptides (triglycine and trileucine), which differ markedly in solubility and molecular weight, have been investigated by jejunal perfusion in healthy human volunteers. Rates of glycine or leucine uptake from test solutions containing triglycine or trileucine were greater than from test solutions containing corresponding amounts of free glycine or free leucine, respectively. The rate of glycine uptake from a 100 mM triglycine solution was greater than that from a 150 mM diglycine solution. At each infused load of triglycine (e.g., 1,000 μmol/min) the rate (micromoles/min. per 30 cm) of either triglycine disappearance (810±40) or glycine absorption (2,208±122) were markedly greater than the luminal accumulation rates of either diglycine (56±10) or free glycine (110±18). The luminal accumulation rate of free leucine during infusion of a 5 mM trileucine solution was over threefold greater than that of free glycine during the infusion of a 5 mM triglycine solution. Luminal fluid exhibited no hydrolytic activity against triglycine, but contained some activity against trileucine. Saturation of free amino acid carrier system with a large load of leucine did not affect glycine absorption rate from a triglycine test solution, but isoleucine markedly inhibited the uptake of leucine from a trileucine solution. When the carrier system for dipeptides was saturated with a large amount of glycylleucine, the disappearance rate of triglycine was considerably reduced while that of trileucine remained unaffected. After addition of glycylleucine to tripeptide solutions, there was a minimal increase in the luminal accumulation of diglycine, while dileucine accumulation was increased by 62 fold. These studies suggest that the modes of intestinal disappearance of the above two tripeptides are different. Triglycine is taken up intact by human jejunum; this uptake is mediated totally or partially by the carrier system which also transports dipeptides. In contrast, trileucine is hydrolyzed to leucine and dileucine mostly on the cell surface and a small fraction is hydrolyzed in the gut lumen; these hydrolytic products are then taken up by the free amino acid and dipeptide carrier systems, respectively.