A B S T R A C T 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 imol/min) the rates (micromoles/minute 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 glycyl-A preliminary account of this work has been previously published (1974. Gastroenterology. 66: 657) leucine, 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.
To define the metabolism of 7-ketolithocholic acid in man, studies were carried out in gallstone patients with normal liver function. 7-[24-14C]ketolithocholic acid or its glycine or taurine conjugates were injected intravenously, and the chemical form of radioactivity appearing in bile was determined to define hepatic biotransformation. To study intestinal absorption 7-[24-14C]ketolithocholic acid was infused into the jejunum and ileum, respectively, and the chemical form of radioactivity appearing in peripheral blood and bile was assessed. 7-Ketolithocholic acid was extensively reduced in the liver to chenic acid and, to lesser extent, to ursodeoxycholic acid. Hepatic reduction was similar for both unconjugated as well as glycine- and taurine-conjugated 7-ketolithocholic acid. 7-Ketolithocholic acid was well absorbed. There was no biotransformation in the small intestinal lumen or during absorption, because all radioactivity recovered from the lumen or in peripheral blood was in unchanged 7-ketolithocholic acid. Biotransformation products in bile after jejunal infusion were similar to those after intravenous injection. The studies indicate that 7-ketolithocholic acid is likely to be a physiological precursor of ursodeoxycholic acid in healthy man.
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