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

Hongyu Hu, Jerzy A. Jaskiewicz, Robert A. Harris

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Ethanol inhibited glucose synthesis from α-ketoisovalerate by isolated rat hepatocytes without significant inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex. Accumulation of 3-hydroxyisobutyrate, an intermediate in the catabolism of α-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 α-ketoacid dehydrogenase. Oleate also inhibited glucose synthesis from α-ketoisovalerate, but marked inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex was caused by this substrate.

Original languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalArchives of Biochemistry and Biophysics
Issue number1
StatePublished - Nov 15 1992


ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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