Kinetic mechanism of monoamine oxidase A.
Steady-state kinetic data for monoamine oxidase A in crude extracts suggest an exclusively ping-pong mechanism, in contrast to those for monoamine oxidase B, which indicate alternate mechanisms involving either a binary or ternary complex. In this study, with use of purified monoamine oxidase A, steady-state data for the inhibition by D-amphetamine of the oxidation of primary amines indicate the possibility of a ternary complex mechanism for monoamine oxidase A also. Stopped-flow studies demonstrate that the rate of reoxidation of reduced enzyme is enhanced by substrates but not by the product, 1-methyl-4-phenylpyridinium. Thus, for the A enzyme, the ternary complex with substrate, but not product, is reoxidized at a faster rate than the free, reduced enzyme. For both the A and B forms of monoamine oxidase, the mechanism is determined by competition between alternate pathways on the basis of the relative rate constants and dissociation constants.
Ramsay
R R
RR
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology; D013379:Substrate Specificity / Q000187:drug effects
D000661:Amphetamine; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium