[L-2-hydroxyglutaric aciduria, an error of metabolism].
The neurometabolic disorder L-2-hydroxyglutaric aciduria was recently shown to be due to a defect in L-2-hydroxyglutarate dehydrogenase. This FAD-linked 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 which normally catalyses the interconversion of oxaloacetate and L-malate, but which also catalyses the NADH-dependent conversion of alpha-ketoglutarate to L-2-hydroxyglutarate. Though very slow, this activity accounts for the in vivo formation of L-2-hydroxyglutarate. As the latter compound is most likely toxic, L-2-hydroxyglutarate dehydrogenase catalyses a metabolite repair reaction.
Van Schaftingen
E
E
Laboratoire de Chimie physiologique, de Duve Institute et U.C.L.
D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005977:Glutarates / Q000378:metabolism; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism*; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D062907:Oxaloacetic Acid / Q000378:metabolism
D005977:Glutarates; D007656:Ketoglutaric Acids; C019417:alpha-hydroxyglutarate; D062907:Oxaloacetic Acid; D000429:Alcohol Oxidoreductases; C023858:2-hydroxyglutarate dehydrogenase