Human brain monoamine oxidase type B: mechanism of deamination as probed by steady-state methods.
Recently, evidence has been published which suggests that [Husain, M., Edmondson, D. E., & Singer, T.P. (1982) Biochemistry 21, 595-600] monoamine oxidase [amine:oxygen oxidoreductase (MAO), EC 1.4.3.4] deaminates phenylethylamine and benzylamine via two distinct kinetic pathways which involve either binary or ternary complex formation, respectively. These conclusions were drawn largely from stopped-flow kinetic analysis performed on purified enzyme removed from its native membrane and in the presence of the inhibitory detergent Triton X-100. In this study, d-amphetamine and alternative substrates were used as steady-state probes of the kinetics of deamination by the B form of human brain MAO using native membrane-bound enzyme. Initial velocity studies showed mixed-type patterns for amphetamine inhibition of phenylethylamine, tryptamine, and tyramine when either amine or oxygen was the varied substrate. Slope and intercept vs. amphetamine concentration replots were linear in all cases except for phenylethylamine (hyperbolic); Ki values obtained from linear replots of slope or intercept values were comparable. In contrast, amphetamine was a competitive inhibitor of benzylamine deamination when amine concentration was varied and uncompetitive when oxygen concentration was varied; slope and intercept replots were linear for both. When benzylamine was the alternative substrate inhibitor and tyramine and tryptamine deamination was measured, mixed-type inhibition patterns were obtained when either amine or oxygen concentration was varied; replots of slope and intercept were linear in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
D001921:Brain / Q000201:enzymology*; D003913:Dextroamphetamine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology; D008956:Models, Chemical; D008995:Monoamine Oxidase / Q000302:isolation & purification / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism; D013379:Substrate Specificity; D014363:Tryptamines / Q000378:metabolism; D014439:Tyramine / Q000378:metabolism
D010627:Phenethylamines; D014363:Tryptamines; C029261:phenethylamine; C030820:tryptamine; D008995:Monoamine Oxidase; D003913:Dextroamphetamine; D014439:Tyramine