Isocitrate dehydrogenase (IDH) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. 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 the mitochondrion and peroxisome. Mutations in IDH1 are also implicated in cancer. Originally mutations in IDH1 were detected in an integrated genomic analysis of human glioblastoma multiforme. In addition to being mutated in diffuse gliomas, IDH1 has also been shown to harbor mutations in human acute myeloid leukemia (AML).
