Coupled Oxidation of Keto-Acids with Glutathione

Abstract

WHEN glutathione is oxidized by copper ions or the cytochrome c–cytochrome-oxidase system in the presence of pyruvate, the added pyruvate is partially oxidized to acetic acid and carbon dioxide¹. It was suggested that this reaction occurred by the production of a hemimercaptol compound between pyruvate and glutathione which is oxidized instead of free glutathione. Slater², disproving the hemimercaptol hypothesis, emphasized a model similar to that found by one of us³ for the coupled oxidation of pyruvate by ascorbic acid, which involves the intermediate production of hydrogen peroxide. But the two points made by Slater in support of his postulate have been found to be inconsistent : (1) the chromatic effect of the methylglyoxal–glutathione complex in the ultra-violet, not shown by the pyruvate–glutathione complex, is mainly due to the enediol compound in equilibrium with the thio-ester resulting from the interaction⁴; enediols and thioesters are not likely to be produced by the interaction of glutathione with pyruvate, which forms only mercaptols; (2) the effect of catalase has been thoroughly investigated and we have been unable to reproduce the inhibitory effect reported by Slater. Moreover, (3) we now present evidence that in our experimental conditions a complex between glutathione and pyruvate is actually formed.