Inhibition of citrate oxidation by glyoxylate in rat-liver homogenates

Abstract

The effect of low concentrations (0.001 [image]) of glyoxylate on the oxidative rate of the main intermediates of the tri-carboxylic acid cycle was investigated in respiring rat-liver homogenates.-The addition of glyoxylate had little effect on the endogenous O2 uptake of the homogenate, but produced a small inhibition of the oxidative rate with citrate, D-isocitrate, cis-aconitate, [alpha]-oxoglutarate, succinate, fumerate, malate and pyruvate, and a small increase in the accumulation of citrate. A very marked inhibition of the uptake of O2, and a large accumulation of citrate, occurred when oxaloacetate was the substrate. The oxidation of citrate was inhibited either by glyoxylate alone, after incubation for 20 minutes or by glyoxylate plus oxaloacetate, after incubation for 5 minutes. Both these results indicate that oxaloacetate was necessary for obtaining maximal rates on inhibition. The dependence of citrate accumulation on oxaloacetate and glyoxylate suggests that the 2 substances react together to form an inhibitor of citrate metabolism. This would account for both citrate accumulation and the depressed O2 uptake.