Studies on the regulation of leucine catabolism. III. Effects of dichloroacetate and 2-chloropropionate on leucine oxidation by the heart

R. M. Sans, W. W. Jolly, R. A. Harris

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12 Scopus citations

Abstract

The effect of dichloroacetate, an activator of pyruvate dehydrogenase and a hypoglycemic agent, on the oxidation of leucine by the perfused rat heart was studied. Dichloroacetate is known to promote leucine oxidation by liver with the mechanism involving dichloroacetate conversion to glyoxylate which acts as a substrate for leucine transamination [10]. Dichloroacetate also promotes leucine oxidation by heart, but unlike liver, the site is at the α-ketoisocaproate dehydrogenase step. This conclusion is based on the observation that dichloroacetate increases l-[1-14C]leucine oxidation to 14CO2 but decreases the steady state concentration of α-ketoisocaproate. It also increases the oxidation of [1-14C]-ketoisocaproate but not that of [1-14C]isovalerate. 2-Chloropropionate, another activator of pyruvate dehydrogenase, also stimulates leucine oxidation in the heart. Since 2-chloropropionate is not converted to glyoxylate, it follows that activation of leucine oxidation in the heart by these activators of pyruvate dehydrogenase is not explained by glyoxylate formation. Pyruvate is a very effective inhibitor of α-ketoisocaproate oxidation by the perfused rat heart. Activation of the pyruvate dehydrogenase complex by dichloroacetate lowers the pyruvate content of glucose-perfused hearts and this appears to relieve the pyruvate-mediated inhibition of α-ketoisocaproate oxidation. The exact basis for pyruvate inhibition of α-ketoisocaproate oxidation remains to be established.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalJournal of Molecular and Cellular Cardiology
Volume12
Issue number1
DOIs
StatePublished - Jan 1980

Keywords

  • 2-Chloropropionate
  • Acetate
  • Dichloroacetate
  • Heart
  • Leucine
  • α-Ketoisocaproate dehydrogenase

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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