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L: -2-Hydroxyglutaric aciduria, a disorder of metabolite repair.

Review article
Van Schaftingen E, et al. J Inherit Metab Dis. 2009.


The neurometabolic disorder L: -2-hydroxyglutaric aciduria is caused by mutations in a gene present on chromosome 14q22.1 and encoding L: -2-hydroxyglutarate dehydrogenase. This FAD-linked mitochondrial enzyme catalyses the irreversible conversion of L: -2-hydroxyglutarate to alpha-ketoglutarate. The formation of L: -2-hydroxyglutarate results from a side-activity of mitochondrial L: -malate dehydrogenase, the enzyme that interconverts oxaloacetate and L: -malate, but which also catalyses, very slowly, the NADH-dependent conversion of alpha-ketoglutarate to L: -2-hydroxyglutarate. L: -2-Hydroxyglutarate has no known physiological function in eukaryotes and most prokaryotes. Its accumulation is toxic to the mammalian brain, causing a leukoencephalopathy and increasing the susceptibility to develop tumours. L: -2-Hydroxyglutaric aciduria appears to be the first disease of 'metabolite repair'.


19020988 [Indexed for MEDLINE]

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