Studies on the regulation of leucine catabolism in the liver. Stimulation by pyruvate and dichloroacetate

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Abstract

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, α-ketoisocaproate, are not increased. Measurement of steady state levels of α-ketoisocaproate indicate that both pyruvate and dichloroacetate promote the transamination of L-leucine, thereby increasing the availability of substrate for decarboxylation by the α-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.

Original languageEnglish (US)
Pages (from-to)1481-1487
Number of pages7
JournalJournal of Biological Chemistry
Volume253
Issue number5
StatePublished - Jan 1 1978

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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