The mechanism of oxidation of aldehydes by glyceralde-hyde-3-phosphate dehydrogenase.

It has been demonstrated (1) that the oxidation-reduction of methylglyoxal to lactic acid occurs in two steps. The first step is a condensation of methylglyoxal and reduced glutathione to a thiol ester which is hydrolytically cleaved to lactic acid and reduced glutathione. It was pointed out that such a mechanism might be operative in other aldehyde-oxidizing systems such as glyceraldehyde phosphate dehydrogenase, and the possibility of obtaining energy-rich phosphate by phosphorolysis of the thiol ester was postulated. The requirement for CoA’ for the oxidation of pyruvic acid (2, 3), of acetaldehyde (4, 5), and of ketoglutaric acid (6, 7) has been demonstrated recently. The discovery by Lynen et al. (8) that acetyl CoA isolated from yeast is a thiol ester of CoA sheds considerable light on the mechanism by which these keto acids and aldehydes’ are oxidized. It has been proposed by Warburg and Christian (9) that the oxidation of glyceraldehyde-3-phosphate consists of the non-enzymatic uptake of phosphate by the aldehyde group, with the formation of 1,3-diphosphoglyceraldehyde, which is oxidized to the corresponding diphosphoglyceric acid. While evidence for the formation of diphosphoglyceric acid was obtained, the formation of the diphosphoglyceraldehyde remained hypothetical. Meyerhof and his collaborators (10, 11) reinvestigated this problem by equilibrium studies and came to the conclusion that inorganic phosphate does not participate in the reaction in the absence of triosephosphate dehydrogenase. The finding of glutathione as a firmly bound group of the enzyme (12) and studies on the glyoxalase enzymes which were carried out at the same time suggested another possible mechanism for triose phosphate oxidation in which the SH group takes an active part in the reaction. In the accompanying scheme it was proposed (1) that the aldehyde group combines with