Erschienen in:
01.04.2009 | Ssiem Symposium 2008
l-2-Hydroxyglutaric aciduria, a disorder of metabolite repair
verfasst von:
E. Van Schaftingen, R. Rzem, M. Veiga-da-Cunha
Erschienen in:
Journal of Inherited Metabolic Disease
|
Ausgabe 2/2009
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Summary
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’.