Fig. 1. Normal functions and subcellular locations of IDH1, IDH2, and IDH3.
All three enzymes oxidize isocitrate (ISO) to alpha-ketoglutarate (α-KG). IDH1 and IDH2 are homodimers, whereas IDH3 is a heterotetramer. IDH1 and IDH2 utilize nicotinamide adenine dinucleotide phosphate (NADP+) as a cofactor, generating NADPH. IDH3 uses NAD+ and produces NADH. IDH2 and 3 are located in mitochondria while IDH1 is in the cytosol and peroxisomes. In certain circumstances IDH1 and IDH2 can reduce α-KG to isocitrate, whereas IDH3 is unidirectional. (The structure in the upper left of the cell depicts a nucleus.)