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.
ASJC Scopus subject areas
- Molecular Biology