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Mutation of either IDH1 or IDH2 imparts a "neomorphic enzymatic activity" on the encoded enzymes, resulting in the gain-of-function ability to convert alpha-ketoglutarate (α-KG) into the oncometabolite 2-hydroxyglutarate (2-HG), while simultaneously converting NADPH to NADP+.
Abbreviations: 2-HG, 2-hydroxyglutarate; α-KG, alpha-ketoglutarate; IDH, isocitrate dehydrogenase; NADP+/NADPH nicotinamide adenine dinucleotide phosphate; PDH, pyruvate dehydrogenase.
(Source: Guo J, Zhang R, Yang Z, Duan Z, Yin D, Zhou Y. Biological roles and therapeutic applications of IDH2 mutations in human cancer. Front Oncol 2021;11:644857. Creative Commons Attribution License [CC BY].)