title: Catalytic and inhibitor binding properties of zebrafish monoamine oxidase (zMAO): comparisons with human MAO A and MAO B.
abstract: A comparative investigation of substrate specificity and inhibitor binding properties of recombinant zebrafish (Danio rerio) monoamine oxidase (zMAO) with those of recombinant human monoamine oxidases A and B (hMAO A and hMAO B) is presented. zMAO oxidizes the neurotransmitter amines (serotonin, dopamine and tyramine) with k(cat) values that exceed those of hMAO A or of hMAO B. The enzyme is competitively inhibited by hMAO A selective reversible inhibitors with the exception of d-amphetamine where uncompetitive inhibition is exhibited. The enzyme is unreactive with most MAO B-specific reversible inhibitors with the exception of chlorostyrylcaffeine. zMAO catalyzes the oxidation of para-substituted benzylamine analogs exhibiting (D)k(cat) and (D)(k(cat)/K(m)) values ranging from 2 to 8. Structure-activity correlations show a dependence of log k(cat) with the electronic factor σ(p) with a ρ value of +1.55±0.34; a value close to that for hMAO A but not with MAO B. zMAO differs from hMAO A or hMAO B in benzylamine analog binding correlations where an electronic effect (ρ=+1.29±0.31) is observed. These data demonstrate zMAO exhibits functional properties similar to hMAO A as well as exhibits its own unique behavior. These results should be useful for studies of MAO function in zebrafish models of human disease states.
authors.affiliation: Department of Biochemistry and Chemistry, Emory University, Atlanta, GA 30322, USA.
authors.forename: Milagros
authors.initials: M
authors.lastname: Aldeco
authors.forename: Betül Kacar
authors.initials: BK
authors.lastname: Arslan
authors.forename: Dale E
authors.initials: DE
authors.lastname: Edmondson
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000378:metabolism; D001665:Binding Sites; D055162:Biocatalysis / Q000187:drug effects; D003913:Dextroamphetamine / Q000737:chemistry / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D010843:Pichia; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D013379:Substrate Specificity; D014439:Tyramine / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011994:Recombinant Proteins; D012701:Serotonin; D008995:Monoamine Oxidase; D003913:Dextroamphetamine; D004298:Dopamine; D014439:Tyramine