Catalytic and Inhibitor Binding Properties of Zebrafish Monoamine Oxidase (zMAO): Comparisons with human MAO A and MAO B

• Authors: Milagros Aldeco, Emory University; Betul Kacar Arslan, Emory University; Dale E Edmondson, Emory University
• Journal Title: Comparative Biochemistry and Physiology - Part B: Biochemistry and Molecular Biology
• Volume: Volume 159, Number 2
• Publisher: Elsevier: 12 months | 2011-06, Pages 78-83
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.cbpb.2011.02.002
• Subjects: Chemistry, Biochemistry; Biology, Molecular
• Keywords: zebrafish; monoamine oxidase; inhibitor binding; substrate specificity

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 kcat 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 analogues exhibiting Dkcat and D(kcat/Km) values ranging from 2–8. Structure-activity correlations show a dependence of log kcat with the electronic factor σp 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 analogue 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.