Isocitrate dehydrogenase (IDH) enzymes catalyze the oxidative decarboxylation of isocitrate to form α-ketoglutarate and contribute to the circuitry of central metabolism. Mammalian IDH1 and IDH2 are NADP-dependent enzymes that exist as homodimers and catalyze the reversible conversion of isocitrate to α-ketoglutarate. In contrast, mammalian IDH3 is a mitochondrial, NAD-dependent heterotetramer comprising two catalytic alpha subunits together with regulatory beta and gamma subunits. IDH3 strictly catalyzes the forward reaction, and is the key enzyme driving the tricarboxylic acid cycle by supplying α-ketoglutarate from the isocitrate pool. (Adapted from PMID:28375741 and PMID:28139779.)