Fig. 1.

In physiological conditions, IDH1/2 metabolizes isocitrate to a-KG with the production of NADPH and CO2. Cancerous mutated IDH1/2 synthesizes 2-HG and NADP+ from a-KG. 2-HG competitively inhibits numerous a-KG-dependent-dixoxygenases. Here illustrated is 2-HG‘s competitive inhibition of JHDMs and TET1/2, which results in histone and DNA methylation, respectively. 2-HG also inhibits ALKBHs, leading to less DNA repair of methylation damage. Overall, these effects induced by 2-HG alter the epigenome of glioma cells and promote tumorigenesis Isocitrate