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Inhibition of Carbohydrate Metabolism by Oxygen and N-Ethylmaleimide in Rat Heart Homogenates

From the ¹ From the Department of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

The inhibitory effects of oxygen and N-ethylmaleimide upon glycolysis and adenosine triphosphate accumulation in rat heart homogenate systems were studied. The main effect of N-ethylmaleimide was to inhibit ATP synthesis and thus to decrease the phosphorylation of glucose and fructose 6-phosphate. It is likely that this compound exerts its action by interfering with reactions of the tricarboxylic acid cycle or electron transport. Oxygen at a pressure of 1 atm was found to inhibit glycolysis directly. The experiments provide strong evidence that the mechanism of this inhibitory effect of oxygen involves the inactivation of glyceraldehyde 3-phosphate dehydrogenase by oxidation of enzyme sulfhydryl groups. Depression of glycolysis by oxygen was prevented by reduced glutathione, cysteine, and dithiothreitol. Some protection against oxygen toxicity was afforded by ascorbic acid. Addition of dithiothreitol or reduced glutathione to a homogenate system inhibited by oxygen caused a reversal of the toxic effects of oxygen.

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