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Neomorphic enzyme activity of mutant IDH enzymes. IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to generate αKG, using NADP+ as a cofactor and producing NADPH and CO2. Recurrent mutations in the active site of IDH1 and IDH2 confer a gain-of-function activity that catalyzes the conversion of αKG into D2HG in a manner that consumes NADPH.
