Reactome: A Curated Pathway Database

Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate (R-HSA-2978092)

Species Homo sapiens


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).

Locations in the PathwayBrowser
Additional Information
Compartment cytosol
GO Biological Process 2-oxoglutarate metabolic process (0006103)
Name Identifier Synonyms
adult glioblastoma multiforme 3075 [grade IV adult Astrocytic tumor]
Literature References
pubMedId Title Journal Year
18772396 An integrated genomic analysis of human glioblastoma multiforme Science 2008
19935646 Cancer-associated IDH1 mutations produce 2-hydroxyglutarate Nature 2009