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Author Notes:

Correspondence: Department of Biochemistry, Emory University, 1510 Clifton Road, Atlanta, Georgia USA 30322; Phone: 01-404-727-5972; Fax: 01-404-727-2738; Email: deedmon@emory.edu

Authors' Contributions: MA and BKA contributed equally to the experimental work described in this manuscript.

Disclosures: The authors thank Drs. Jin Wang, Claudia Binda, and Andrea Mattevi for helpful discussions.

Subjects:

Research Funding:

This work was supported by National Institutes of Health grant GM-29433 to DEE.

Keywords:

  • zebrafish
  • monoamine oxidase
  • inhibitor binding
  • substrate specificity

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

Tools:

Journal Title:

Comparative Biochemistry and Physiology - Part B: Biochemistry and Molecular Biology

Volume:

Volume 159, Number 2

Publisher:

, Pages 78-83

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2011 Elsevier Inc. All rights reserved

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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