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Regulation of leucine catabolism 3. effects of di chloro acetate and 2 chloro propionate on leucine oxidation by the heart






Journal of Molecular and Cellular Cardiology 12(1): 1-16

Regulation of leucine catabolism 3. effects of di chloro acetate and 2 chloro propionate on leucine oxidation by the heart

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 promotes leucine oxidation in the liver with the mechanism involving dichloroacetate conversion to glyoxylate which acts as a substrate for leucine transamination. Dichloroacetate promotes leucine oxidation in the heart but, unlike liver, the site occurs at the .alpha.-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 .alpha.-ketoisocaproate. It increases the oxidation of [1-14C]-ketoisocaproate but not that of [1-14C]isovalerate. 2-Chloropropionate, another activator of pyruvate dehydrogenase stimulates leucine oxidation in the heart. Since 2-chloropropionate is not converted to glyoxylate, activation of leucine oxidation in the heart by these activators of pyruvate dehydrogense is not explained by glyoxylate formation. Pyruvate is a very effective inhibitor of .alpha.-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 .alpha.-ketoisocaproate oxidation. The exact basis for pyruvate inhibition of .alpha.-ketoisocaproate oxidation is unknown.


Accession: 006288985



Related references

Sans R.M.; Jolly W.W.; Harris R.A., 1980: Regulation of leucine catabolism mechanism responsible for oxidizable substrate inhibition and di chloro acetate stimulation of leucine oxidation by the heart. In the absence of any other oxidizable substrate, the perfused rat heart oxidizes [1-14C]-leucine to 14CO2 at a rapid rate and releases only small amounts of .alpha.[1-14C]ketoisocaproate into the perfusion medium. The branched-chain .alpha.-keto...

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Sans R.M., 1979: Effect of di chloro acetate on leucine catabolism by perfused heart. Federation Proceedings 38(3 PART 1): 829

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