title: L: -2-Hydroxyglutaric aciduria, a disorder of metabolite repair.
abstract: 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'.
authors.affiliation: de Duve Institute, Université catholique de Louvain, Brussels, Belgium. emile.vanschaftingen@uclouvain.be
authors.forename: E
authors.initials: E
authors.lastname: Van Schaftingen
authors.forename: R
authors.initials: R
authors.lastname: Rzem
authors.forename: M
authors.initials: M
authors.lastname: Veiga-da-Cunha
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005977:Glutarates / Q000652:urine*; D006801:Humans; D009243:NAD / Q000378:metabolism; D009422:Nervous System Diseases / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D005977:Glutarates; D009243:NAD; D005182:Flavin-Adenine Dinucleotide; C019417:alpha-hydroxyglutarate; D000429:Alcohol Oxidoreductases; C023858:2-hydroxyglutarate dehydrogenase