A CROSS-INHIBITION OF BASIC AMINO ACID TRANSPORT BY NEUTRAL AMINO ACIDS

1. 1. At a concentration of 12.5 mM the neutral amino acids inhibited the transport of 1 mM lysine by everted intestinal sacs from the rat in a manner related to their affinity for the neutral amino acid carrier. Leucine and methinine induced a large net flux of lysine from the tissue to the mucosal medium at the lysine steady state while sugars did not, indicating an interaction of the amino acids at the carrier level rather than one due to energy limitations. Leucine and methionine produced a large competitive stimulation of lysine transport, while arginine under the same conditions was inhibitory. This result implies independent carrier systems for the neutral and basic acids. Valine was found to be a partial competitive inhibitor of lysine transport in contrast to arginine which produced total inhibition. The 10-15% inhibition of valine transport produced by lysine at concentrations between 25 and 100 mM was not found to be competitive. The findings that valine and lysine have the same distribution of transport activity along the intestine and that valine produced a constant inhibition of lysine transport as a function of intestinal location suggests that valine and lysine are not transported by different carrier systems and is consistent with transport by spatially related carrier systems. 2. 2. These results are best explained by an allosteric modification of the basic amino acid site caused by the binding of a neutral amino acid to a structurally specific but closely associated site on a single or polyfunctional carrier. © 1969.