Inhibition, by 2‐Oxo Acids That Accumulate in Maple‐Syrup‐Urine Disease, of Lactate, Pyruvate, and 3‐Hydroxybutyrate Transport Across the Blood‐Brain Barrier

Inhibition, by 2‐Oxo Acids That Accumulate in Maple‐Syrup‐Urine Disease, of Lactate,... Abstract: Data are presented in support of the transport of (‐)‐d‐3‐hydroxybutyrate across the blood‐brain barrier (BBB) being a carrier‐mediated process. The kinetic parameters in 21‐day‐old pentobarbital‐anaesthetized rats were Vmax 2.0 μmol.g−1.min−1, Km 29 mM, and KD 0.024 ml.g−1.min−1. The value for Vmax was the same as that for l‐lactate and pyruvate transport in animals of the same age. The transport of all three substrates was sensitive to inhibition by low concentrations of either 2‐oxo‐3‐methylbutanoate or 2‐0x0‐4‐methylpentanoate, the 2‐oxo acids that can accumulate in patients with maple‐syrup‐urine disease. The Km values for the 2‐oxo acids were severalfold lower than the respective Km values. 2‐oxo‐3‐phenylpropionate was a poor inhibitor. The relative affinities of the various monocarboxylic acids for the transport system of the BBB distinguished it from similar systems described in brain, heart, and liver mitochondria; human erythrocytes; and Ehrlich ascites‐tumour cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Inhibition, by 2‐Oxo Acids That Accumulate in Maple‐Syrup‐Urine Disease, of Lactate, Pyruvate, and 3‐Hydroxybutyrate Transport Across the Blood‐Brain Barrier

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Publisher
Wiley
Copyright
Copyright © 1982 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1982.tb07945.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: Data are presented in support of the transport of (‐)‐d‐3‐hydroxybutyrate across the blood‐brain barrier (BBB) being a carrier‐mediated process. The kinetic parameters in 21‐day‐old pentobarbital‐anaesthetized rats were Vmax 2.0 μmol.g−1.min−1, Km 29 mM, and KD 0.024 ml.g−1.min−1. The value for Vmax was the same as that for l‐lactate and pyruvate transport in animals of the same age. The transport of all three substrates was sensitive to inhibition by low concentrations of either 2‐oxo‐3‐methylbutanoate or 2‐0x0‐4‐methylpentanoate, the 2‐oxo acids that can accumulate in patients with maple‐syrup‐urine disease. The Km values for the 2‐oxo acids were severalfold lower than the respective Km values. 2‐oxo‐3‐phenylpropionate was a poor inhibitor. The relative affinities of the various monocarboxylic acids for the transport system of the BBB distinguished it from similar systems described in brain, heart, and liver mitochondria; human erythrocytes; and Ehrlich ascites‐tumour cells.

Journal

Journal of NeurochemistryWiley

Published: Sep 1, 1982

References

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