Inhibition, by 2-oxo acids that accumulate in maple-syrup-urine disease, of lactate, pyruvate, and 3-hydroxybutyrate transport across the blood-brain barrier

J Neurochem. 1982 Sep;39(3):674-7. doi: 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-anaesthetized rats were Vmax 2.0 mumol.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-oxo-4-methylpentanoate, the 2-oxo acids that can accumulate in patients with maple-syrup-urine disease. The Ki 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.

MeSH terms

  • 3-Hydroxybutyric Acid
  • Animals
  • Blood-Brain Barrier / drug effects*
  • Brain / metabolism
  • Humans
  • Hydroxybutyrates / metabolism*
  • Keto Acids / metabolism
  • Keto Acids / pharmacology*
  • Kinetics
  • Lactates / metabolism*
  • Lactic Acid
  • Maple Syrup Urine Disease / metabolism*
  • Pyruvates / metabolism*
  • Pyruvic Acid
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Hydroxybutyrates
  • Keto Acids
  • Lactates
  • Pyruvates
  • Lactic Acid
  • Pyruvic Acid
  • 3-Hydroxybutyric Acid