Inhibition of branched-chain amino acid degradation by ketone bodies.
The present study deals with mechanisms for the accumulation of intermediates in the catabolism of branched-chain amino acids in patients with ketoacidosis. Two different systems have been developed to measure the degradation rates of leucine and valine intermediates in rat liver mitochondria. 3-Hydroxybutyrate was found to inhibit the conversion of isobutyryl-CoA to propionyl-CoA, and this appeared to be partly due to an elevated NADH2/NAD ratio. 3-Methylcrotonyl-CoA carboxylase was strongly inhibited by acetoacetyl-CoA and to a lesser extent by the nonesterified ketone bodies. These inhibitory effects of ketone bodies may explain the accumulation of branched-chain amino acid intermediates during ketoacidosis.
D000818:Animals; D002087:Butyrates / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D051381:Rats; D014633:Valine / Q000378:metabolism*
D002087:Butyrates; D007657:Ketone Bodies; D007930:Leucine; D014633:Valine; D003065:Coenzyme A