Nicotinamide adenine dinucleotide phosphate linked isocitrate dehydrogenase. Catalytic activation by the reduced coenzyme product of the reaction

The oxidative decarboxylation of D-isocitrate catalyzed by NADP-linked isocitrate dehydrogenase is activated by NADPH, the product of the reaction. We analyzed the autocatalytic behavior exhibited by the enzyme during the steady-state kinetics. NADP acts as a competitive inhibitor toward NADPH in the catalytic activation. In a large concentration range of the reduced and oxidized coenzymes, the activity of the enzyme is proportional to the ratio (NADPH)/(NADP). The results are compared with the results of experiments done with other NADP-linked decarboxylating dehydrogenases. Two different models are presented in order to explain the mechanism of action of isocitrate dehydrogenase, according to our data.