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The roles of isocitrate dehydrogenases in cancer metabolism

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].)

Associated Disorders

  • Ataxia
  • Cardiomyopathy
  • Cerebellar atrophy
  • Dystonia
  • Mental retardation
  • Primary brain tumors
  • Progressive intellectual deterioration
  • Seizures
  • Subcortical leukoencephalopathy