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Inhibition, by 2‐Oxo Acids That Accumulate in Maple‐Syrup‐Urine Disease, of Lactate, Pyruvate, and 3‐Hydroxybutyrate Transport Across the Blood‐Brain Barrier
Author(s) -
Cremer Jill E.,
Teal Hazel M.,
Cunningham Vincent J.
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb07945.x
Subject(s) - maple syrup urine disease , chemistry , metabolism , blood–brain barrier , biochemistry , medicine , endocrinology , biology , amino acid , central nervous system , leucine
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 V max 2.0 μmol.g −1 .min −1 , K m 29 m M , and K D 0.024 ml.g −1 .min −1 . The value for V max 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 K m values for the 2‐oxo acids were severalfold lower than the respective K m 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.