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

KINETICS OF COMPETITIVE INHIBITION OF NEUTRAL AMINO ACID TRANSPORT ACROSS THE BLOOD‐BRAIN BARRIER 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 (14C)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 K1 (determined from cross‐inhibition studies) and the Km (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 Km values are computed for the essential neutral amino acids from known data on amino acid transport Km and plasma concentrations. The apparent Km 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

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

Journal of Neurochemistry, Volume 28 (1) – Jan 1, 1977

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Publisher
Wiley
Copyright
Copyright © 1977 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
DOI
10.1111/j.1471-4159.1977.tb07714.x
Publisher site
See Article on Publisher Site

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 (14C)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 K1 (determined from cross‐inhibition studies) and the Km (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 Km values are computed for the essential neutral amino acids from known data on amino acid transport Km and plasma concentrations. The apparent Km 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.

Journal

Journal of NeurochemistryWiley

Published: Jan 1, 1977

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