Inhibition, by 2‐Oxo Acids That Accumulate in Maple‐Syrup‐Urine Disease, of Lactate, Pyruvate, and 3‐Hydroxybutyrate Transport Across the Blood‐Brain Barrier
- 1 September 1982
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 39 (3), 674-677
- https://doi.org/10.1111/j.1471-4159.1982.tb07945.x
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-anesthetized rats were Vmax 2.0 .mu.mol.cntdot.g-1.cntdot.min-1, Km 20 mM and Kd 0.024 ml.cntdot.g-1.cntdot.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 3 substrates was sensitive to inhibition by low concentrations of either 2-oxo-3-methylbutanoate or 2-oxo-4-methylpentanoate, the 2-oxo acids that can accumulate in patients with maple-syrup-urine disease. The Ki (inhibition constant] 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-tumor cells.Keywords
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