Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate

Stable Identifier
Homo sapiens
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Somatic mutations affecting arginine residue 132 of IDH1 (isocitrate dehydrogenase 1, a cytosolic enzyme that normally catalyzes the NADP+-dependent conversion of isocitrate to 2-oxoglutarate), are very commonly found in human glioblastomas (Parsons et al. 2008). These mutant proteins efficiently catalyze the NADPH-dependent reduction of 2-oxoglutarate to form 2-hydroxyglutarate. Cells expressing the mutant protein accumulate elevated levels of 2-hydroxyglutarate, probably in the cytosol as IDH1 is a cytosolic enzyme. The fate of the 2-hydroxyglutarate is unclear, but the high frequency with which the mutation is found in surveys of primary tumors is consistent with the possibility that it is advantageous to the tumor cells (Dang et al 2009).
Literature References
PubMed ID Title Journal Year
19935646 Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

Keenan, MC, White, DW, Su, SM, Liau, LM, Yen, KE, Bittinger, MA, Gross, S, Fantin, VR, Dang, L, Thompson, CB, Jin, S, Cantley, LC, Rabinowitz, JD, Ward, PS, Bennett, BD, Jang, HG, Marks, KM, Prins, RM, Vander Heiden, MG, Driggers, EM

Nature 2009
18772396 An integrated genomic analysis of human glioblastoma multiforme

Bigner, DD, McLendon, R, Gallia, GL, Strausberg, RL, Karchin, R, Mankoo, P, Papadopoulos, N, Marie, SK, Parsons, DW, Hartigan, J, Kinzler, KW, Nikolsky, Y, Vogelstein, B, Diaz Jr, LA, Angenendt, P, Shinjo, SM, Velculescu, VE, Lin, JC, Jones, S, Parmigiani, G, Zhang, X, Leary, RJ, Yan, H, Smith, DR, Nikolskaya, T, Riggins, GJ, Keir, S, Olivi, A, Rasheed, BA, Siu, IM, Carter, H, Tekleab, H, Busam, DA

Science 2008
Event Information
Name Identifier Synonyms
glioblastoma multiforme DOID:3068 GBM, adult glioblastoma multiforme, grade IV adult Astrocytic tumor, primary glioblastoma multiforme, spongioblastoma multiforme
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