Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R-2-hydroxyglutarate. Elevated levels of R-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors.
Pathway
2-Oxocarboxylic acid metabolism; Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate; Biosynthesis of amino acids; Carbon metabolism
Citations
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