Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to 2-oxoglutarate. Mutations of Arg-132 in IDH to Cys, His, Leu or Ser abolish magnesium binding and 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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