THE OXIDATION OF LEUCINE BY EHRLICH ASCITES CARCINOMA CELLS

Abstract

The oxidation of leucine-1-14C to14CO2by Ehrlich ascites carcinoma cells was inhibited on addition of pyruvate and other α-keto acids, a maximum inhibitory effect being attained with 1 mM pyruvate. The only compound, among those tested, which reversed this inhibition was malonate. Oxidation of leucine-2-14C to14CO2occurred at a rate which was 1% of that observed with leucine-1-14C and was sensitive to the presence of fatty acids as well as to pyruvate. Glutamine was a particularly effective inhibitor of leucine oxidation. The inhibition produced by isoleucine was competitive, the KIvalue being 0.13 mM compared with the KMvalue of 0.2 mM. It is suggested that the inhibition by pyruvate is due to a competition between pyruvate and the α-ketoisovaleric acid derived from leucine for the cofactors required for the oxidation of the α-keto acids. In contrast, oxidation of leucine-1-14C by mouse liver slices was increased approximately threefold by pyruvate.