Isocitrate dehydrogenase 1 (IDH1) mutations are found in the majority of low-grade gliomas and secondary glioblastoma. IDH1 mutants convert 2-oxoglutarate (2OG) to 2-hydroxyglutarate (2HG), which inhibits 2OG-dependent dioxygenases and leads to changes in the epigenetic landscape of gliomas. However, cells also have other 2OG-dependent enzymes, including transaminases that catalyze the production of glutamate needed for the production of the antioxidant glutathione. Previous work showed that IDH mutant cells have decreased levels of branched-chain α-ketoacids, which are made from the branched-chain amino acids (BCAA) by the transaminases BCAT1 and BCAT2, suggesting that these transaminases are inhibited in IDH mutant cells.
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