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

Milagros Aldeco, Betül Kacar Arslan, Dale E. Edmondson

Research output: Contribution to journalArticle

20 Scopus citations

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 analogs exhibiting Dkcat and D(kcat/Km) values ranging from 2 to 8. Structure-activity correlations show a dependence of log kcat with the electronic factor σp with a σ 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 (σ=+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.

Original languageEnglish (US)
Pages (from-to)78-83
Number of pages6
JournalComparative Biochemistry and Physiology - B Biochemistry and Molecular Biology
Volume159
Issue number2
DOIs
StatePublished - Jun 2011

Keywords

  • Inhibitor binding
  • Monoamine oxidase
  • Substrate specificity
  • Zebrafish

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology

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