Catalytic and inhibitor binding properties of zebrafish monoamine oxidase (zMAO): Comparisons with human MAO A and MAO B

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 sigma(p) with a rho 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 (rho = +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. (C) 2011 Elsevier Inc. All rights reserved.