Deficiency of 3-methylglutaconyl-coenzyme A hydratase in two siblings with 3-methylglutaconic aciduria.
We studied two patients with 3-methylglutaconic aciduria in order to determine the molecular defect. A new assay for 3-methylglutaconyl-coenzyme A (CoA) hydratase has been developed in which the substrate, [5-14C]3-methylglutaconyl-CoA, was synthesized using 3-methylcrotonyl-CoA carboxylase purified from bovine kidney. In this assay the products of the reaction are isolated by reverse-phase high performance liquid chromatography and the rates of conversion from substrate are measured. The Michaelis constant for 3-methylglutaconyl-CoA in normal fibroblasts was 6.9 mumol/liter. The mean activity of 3-methylglutaconyl-CoA hydratase in control fibroblasts was 495 pmol/min per mg protein. In the two patients the values were 11 and 17 pmol/min per mg protein, or 2-3% of normal.
Narisawa
K
K
Gibson
K M
KM
Sweetman
L
L
Nyhan
W L
WL
Duran
M
M
Wadman
S K
SK
D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000652:urine; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D005977:Glutarates / Q000652:urine*; D006801:Humans; D006836:Hydro-Lyases / Q000172:deficiency*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008596:Menotropins / Q000378:metabolism
D005977:Glutarates; C022034:3-methylglutaconic acid; D008596:Menotropins; D006836:Hydro-Lyases; C035867:methylglutaconyl-CoA hydratase