TAILIEUCHUNG - Báo cáo khoa học: Biochemical characterization of human 3-methylglutaconyl-CoA hydratase and its role in leucine metabolism

The metabolic disease 3-methylglutaconic aciduria type I (MGA1) is char-acterized by an abnormal organic acid profile in which there is excessive urinary excretion of 3-methylglutaconic acid, 3-methylglutaric acid and 3-hydroxyisovaleric acid. Affected individuals display variable clinical manifestations ranging from mildly delayed speech development to severe psychomotor retardation with neurological handicap. | iFEBS Journal Biochemical characterization of human 3-methylglutaconyl-CoA hydratase and its role in leucine metabolism Matthias Mack1 Ute Schniegler-Mattox2 Verena Peters3 Georg F. Hoffmann3 Michael Liesert4 Wolfgang Buckel4 and Johannes Zschocke2 1 Institut fur Technische Mikrobiologie der Hochschule Mannheim Germany 2 Institut fur Humangenetik Ruprecht-Karls-Universitat Heidelberg Germany 3 Abteilung fur Allgemeine Padiatrie Ruprecht-Karls-Universitat Heidelberg Germany 4 Labor fur Mikrobiologie der Philipps-Universitat-Marburg Germany Keywords leucine metabolism 3-methylglutaconic aciduria type I 3-methylglutaconyl-coenzyme A hydratase AUH Correspondence M. Mack Institut fur Technische Mikrobiologie der Hochschule Mannheim Windeckstr. 110 68163 Mannheim Germany Fax 49 6212926420 Tel 49 6212926496 E-mail Received 14 September 2005 revised 3 March 2006 accepted 7 March 2006 doi The metabolic disease 3-methylglutaconic aciduria type I MGA1 is characterized by an abnormal organic acid profile in which there is excessive urinary excretion of 3-methylglutaconic acid 3-methylglutaric acid and 3-hydroxyisovaleric acid. Affected individuals display variable clinical manifestations ranging from mildly delayed speech development to severe psychomotor retardation with neurological handicap. MGA1 is caused by reduced or absent 3-methylglutaconyl-coenzyme A 3-MG-CoA hydratase activity within the leucine degradation pathway. The human AUH gene has been reported to encode for a bifunctional enzyme with both RNA-binding and enoyl-CoA-hydratase activity. In addition it was shown that mutations in the AUH gene are linked to MGA1. Here we present kinetic data of the purified gene product of AUH using different CoA-substrates. The best substrates were E -3-MG-CoA Vmax U-mg-1 Km pM kcat s-1 and E -glutaconyl-CoA Vmax U-mg-1 Km pM kcat s-1 giving strong evidence that the AUH gene encodes for the major .

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