Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma.

doi:10.1016/j.cell.2018.08.038

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Article

Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma.

Cell - 20 Sept 2018

McBrayer Samuel K, Mayers Jared R, DiNatale Gabriel J, Shi Diana D, Khanal Januka, Chakraborty Abhishek A, Sarosiek Kristopher A, Briggs Kimberly J, Robbins Alissa K, Sewastianik Tomasz, Shareef Sarah J, Olenchock Benjamin A, Parker Seth J, Tateishi Kensuke, Spinelli Jessica B, Islam Mirazul, Haigis Marcia C, Looper Ryan E, Ligon Keith L, Bernstein Bradley E, Carrasco Ruben D, Cahill Daniel P, Asara John M, Metallo Christian M, Yennawar Neela H, Vander Heiden Matthew G, Kaelin William G

Abstract excerpt

IDH1 mutations are common in low-grade gliomas and secondary glioblastomas and cause overproduction of (R)-2HG. (R)-2HG modulates the activity of many enzymes, including some that are linked to transformation and some that are probably bystanders. Although prior work on (R)-2HG targets focused on 2OG-dependent dioxygenases, we found that (R)-2HG potently inhibits the 2OG-dependent transaminases BCAT1 and BCAT2,...

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PMID: 30220459
DOI: 10.1016/j.cell.2018.08.038
PMCID: PMC6219629

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