Isocitrate Dehydrogenase (IDH)

Isocitrate dehydrogenase (IDH) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producingalpha-ketoglutarate (α-ketoglutarate) and CO₂. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate(a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD⁺ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP⁺ as a cofactor instead of NAD⁺. They localize to the cytosol as well as themitochondrion and peroxisome.