IDH2 and cancer: IDH1 and IDH2 share significant similarity and catalyse reversible reactions, whereas IDH3 catalyses an irreversible reaction with greater regulation (i.e., calcium, ADP and citrate), however all forms convert isocitrate to α-ketoglutarate while reducing NAD(P)+ to NAD(P)H.248–251 IDH1 localizes (variably) to the cytoplasm and IDH2/3 localise to the mitochondria.252 Examination of several gene expression databases from a range of cancer cell lines displayed co-expression of ME1 mRNA with G6PD and IDH1, indicating a coordination of metabolic pathways that produce NADPH.246