A Multiple Role for the Coenzyme in the Mechanism of Action of 6-Phosphogluconate Dehydrogenase

• Published in: The Journal of biological chemistry Vol. 248; no. 14; pp. 4920 - 4925
• Main Authors: Rippa, Mario, Signorini, Marco, Dallocchio, Franco
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.07.1973; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)43652-1

6-Phosphogluconate dehydrogenase from Candida utilis catalyzes the oxidative decarboxylation of 2-deoxy-6-phosphogluconate. The 3-keto-2-deoxy-6-phosphogluconate, an intermediate of the reaction, is reduced to 2-deoxy-6-phosphogluconate and decarboxylated to 1-deoxyribulose 5-phosphate when incubated with the enzyme and TPNH. The decarboxylation process does not occur in the absence of the reduced coenzyme, which does not have, in this step, an oxidation-reduction role. Since TPNH also has a non-redox role in a tritium exchange reaction catalyzed by the enzyme, it appears that the coenzyme has a multiple role in the mechanism of action of 6-phosphogluconate dehydrogenase: a redox role in the dehydrogenation and another (or others) role(s) in the decarboxylation and tritium exchange reactions. The hydroxyl group present at carbon 2 of 6-phosphogluconate seems to have a dual role in the mechanism of action of the enzyme: one in the binding of the substrate to the enzyme, another in enhancing the decarboxylation of the dehydrogenation product. These findings are discussed with relations to the mechanism of action of isocitrate dehydrogenase and of the malic enzyme. The enzymatic oxidative decarboxylation of 2-deoxy-6-phosphogluconate is a new step for the metabolism of the metabolic inhibitor 2-deoxyglucose.