Figure 2.

Oncogenic mutations in cytoplasmic or mitochondrial IsocitrateDehydrogenases and production of 2-Hydroxyglutarate interfere withα-ketoglutarate-dependent enzymatic functions. Inhibition of branched chainaminoacid aminotransferases decreases glutamate production and enhances thecells’ reliance on Glutaminase for Glutathione synthesis. Inhibition of lysinehistone demethylases can in certain tissue contexts compromise DNA damagerepair, whereas in other cases in can promote homologous recombination andgenomic stability