title: Oxidation of tetrahydrostilbazole by monoamine oxidase A demonstrates the effect of alternate pathways in the kinetic mechanism.
abstract: The steady-state kinetics for the oxidation of 1-methyl-1,2,3,6-tetrahydrostilbazole (MTHS) by purified human liver monoamine oxidase A yielded biphasic double-reciprocal plots. Rate constants from stopped-flow studies were determined to show that the apparent stimulation at high substrate concentrations can be explained in terms of the alternate oxidative pathways available to monoamine oxidase A [Ramsay, R. R. (1991) Biochemistry 30, 4624-4629]. At low substrate concentrations, the slower reoxidation of the free enzyme (second-order rate constant was 4000 M-1 s-1) predominates, but at higher concentrations the faster reoxidation of the reduced enzyme-substrate complex (38,300 M-1 s-1) becomes significant. Computer simulation using this model predicts that similar biphasic curves could be obtained for the oxidation of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, but that nonlinearity would be obvious only at concentrations above 200 Km.
authors.affiliation: Department of Biochemistry and Biophysics, University of California at San Francisco 94143.
authors.forename: R R
authors.initials: RR
authors.lastname: Ramsay
authors.forename: S O
authors.initials: SO
authors.lastname: Sablin
authors.forename: S O
authors.initials: SO
authors.lastname: Bachurin
authors.forename: T P
authors.initials: TP
authors.lastname: Singer
mesh_terms: D001667:Binding, Competitive; D006801:Humans; D007700:Kinetics; D007735:Kynuramine / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008956:Models, Chemical; D008995:Monoamine Oxidase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013343:Styrenes / Q000378:metabolism*
chemical_list: D011725:Pyridines; D011994:Recombinant Proteins; D013343:Styrenes; C083057:1-methyl-1,2,3,6-tetrahydrostilbazole; D007735:Kynuramine; D008995:Monoamine Oxidase; D010100:Oxygen