Biochemical characterization of human 3-methylglutaconyl-CoA hydratase and its role in leucine metabolism.

摘要: The metabolic disease 3-methylglutaconic aciduria type I (MGA1) is characterized by an abnormal organic acid profile in which there excessive urinary excretion of acid, 3-methylglutaric and 3-hydroxyisovaleric acid. Affected individuals display variable clinical manifestations ranging from mildly delayed speech development to severe psychomotor retardation with neurological handicap. MGA1 caused reduced or absent 3-methylglutaconyl-coenzyme A (3-MG-CoA) hydratase activity within the leucine degradation pathway. human AUH gene has been reported encode for a bifunctional enzyme both RNA-binding enoyl-CoA-hydratase activity. In addition, it was shown that mutations are linked MGA1. Here we present kinetic data purified product using different CoA-substrates. best substrates were (E)-3-MG-CoA (V(max) = 3.9 U.mg(-1), K(m) 8.3 microM, k(cat) 5.1 s(-1)) (E)-glutaconyl-CoA 1.1 2.4 1.4 giving strong evidence encodes major 3-MG-CoA degradation. Based on these results, new assay fibroblast homogenates developed. only missense mutation found phenotypes, c.719C>T, leading amino exchange A240V, produces 9% wild-type