Inhibition of branched-chain amino acid degradation by ketone bodies

Abstract

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-Methyl-crotonyl-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.

Key Words:

• hydroxybutyrates
• ketone bodies
• leucine
• valerates
• valine