Mechanisms of inhibition of glycylglycine transport by glycyl-L-leucine and L-leucine in guinea-pig small intestine.

Inhibition of glycylglycine (Gly-Gly) transport by glycyl-L-leucine (Gly-Leu) and L-leucine was studied in isolated guinea-pig ileum. Kinetically, inhibition by Gly-Leu of Gly-Gly influx across the mucosal border was found to be mixed type, whereas the inhibition by leucine was "pseudo-competitive'. Kinetics of Gly-Leu inhibition, which could be defined as linear mixed type, suggests that Gly-Gly transport carrier has a high-affinity binding site for Gly-Leu besides the site for Gly-Gly, and that binding of Gly-Leu to its own site is inhibitory to Gly-Gly transport but independent of Gly-Leu transfer, Gly-Leu hydrolases at the brush border membrane had high-affinity component, but this did not seem to be related to the inhibitory binding of Gly-Leu, since bestatin (0.3 mM) completely suppressed the high-affinity component of the enzymes but little affected Gly-Gly transport. The "pseudo-competitive' type of inhibition by leucine suggests that the Gly-Gly carrier has another binding site to which leucine can bind, that leucine binding to this site is inhibitory to Gly-Gly transport and that leucine is partly transported by the Gly-Gly carrier system.