Ethanol and oleate inhibition of alpha-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes

Arch Biochem Biophys. 1992 Nov 15;299(1):57-62. doi: 10.1016/0003-9861(92)90243-p.

Abstract

Ethanol inhibited glucose synthesis from alpha-ketoisovalerate by isolated rat hepatocytes without significant inhibition of flux through the branched-chain alpha-ketoacid dehydrogenase complex. Accumulation of 3-hydroxyisobutyrate, an intermediate in the catabolism of alpha-ketoisovalerate, was increased by ethanol, indicating inhibition of flux at the level of 3-hydroxyisobutyrate dehydrogenase. 3-Hydroxybutyrate caused the same effects as ethanol, suggesting inhibition was a consequence of an increase in the mitochondrial NADH/NAD+ ratio. Flux through the 3-hydroxyisobutyrate dehydrogenase was more sensitive to regulation by the mitochondrial NADH/NAD+ ratio than flux through the branched-chain alpha-ketoacid dehydrogenase. Oleate also inhibited glucose synthesis from alpha-ketoisovalerate, but marked inhibition of flux through the branched-chain alpha-ketoacid dehydrogenase complex was caused by this substrate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Hydroxybutyric Acid
  • Animals
  • Caprylates / pharmacology
  • Cells, Cultured
  • Ethanol / pharmacology*
  • Glucagon / pharmacology
  • Hemiterpenes
  • Hydroxybutyrates / metabolism*
  • Hydroxybutyrates / pharmacology
  • Keto Acids / metabolism*
  • Kinetics
  • Liver / drug effects
  • Liver / metabolism*
  • Lysine / pharmacology
  • Male
  • Oleic Acid
  • Oleic Acids / pharmacology*
  • Rats

Substances

  • Caprylates
  • Hemiterpenes
  • Hydroxybutyrates
  • Keto Acids
  • Oleic Acids
  • Oleic Acid
  • Ethanol
  • alpha-ketoisovalerate
  • Glucagon
  • Lysine
  • 3-hydroxyisobutyric acid
  • octanoic acid
  • 3-Hydroxybutyric Acid