Studies on the regulation of leucine catabolism in the liver. Stimulation by pyruvate and dichloroacetate.
The rate of oxidation of L-[1-14C]leucine to 14CO2 by isolated rat hepatocytes is increased by pyruvate and dichloroacetate. This effect is specific for L-leucine, not being observed for L-valine, L-isoleucine, or D-leucine. Transamination, the rate-limiting step of L-leucine catabolism in the liver, is the site of stimulation, because uptake of L-leucine by the cells and the oxidation of its transamination product, alpha-ketoisocaproate, are not increased. Measurement of steady state levels of alpha-ketoisocaproate indicate that both pyruvate and dichloroacetate promote the transamination of L-leucine, thereby increasing the availability of substrate for decarboxylation by the alpha-ketoisocaproate dehydrogenase complex (EC 1.2.4.3). Pyruvate stimulation of transamination is secondary to the provision of keto acid acceptors for the amino group of L-leucine. The mechanism of the effect of dichloroacetate remains unknown.
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D007930:Leucine / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011773:Pyruvates / Q000494:pharmacology*; D051381:Rats
D000085:Acetates; D002241:Carbohydrates; D011773:Pyruvates; D003999:Dichloroacetic Acid; D007930:Leucine