KINETICS OF COMPETITIVE INHIBITION OF NEUTRAL AMINO ACID TRANSPORT ACROSS THE BLOOD‐BRAIN BARRIER

Abstract

Abstract— The transport of tryptophan across the blood‐brain barrier is used as a specific example of a general approach by which rates of amino acid influx into brain may be predicted from existing concentrations of amino acids in plasma. The kinetics of inhibition of [ 14 C]tryptophan transport by four natural neutral amino acids (phenylalanine, leucine, methionine, and valine) and one synthetic amino acid (α‐methyl tyrosine) is studied with a tissue‐sampling, single injection technique in the barbiturate‐anesthetized rat. The equality of the K 1 (determined from cross‐inhibition studies) and the K m (determined from auto‐inhibition data) for neutral amino acid transport indicate that these amino acids compete for a single transport site in accordance with the kinetics of competitive inhibition. Based on equations derived for competitive inhibition, apparent K m values are computed for the essential neutral amino acids from known data on amino acid transport K m and plasma concentrations. The apparent K m values make possible predictions of the in vivo rates of amino acid influx into brain based on given plasma amino acid concentrations. Finally, a method is presented for determining transport constants from saturation data obtained with single injection techniques.