PUBLICATION
Catalytic and inhibitor binding properties of zebrafish monoamine oxidase (zMAO): Comparisons with human MAO A and MAO B
- Authors
- Aldeco, M., Arslan, B.K., and Edmondson, D.E.
- ID
- ZDB-PUB-110316-37
- Date
- 2011
- Source
- Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 159(2): 78-83 (Journal)
- Registered Authors
- Edmondson, Dale E.
- Keywords
- Zebrafish, Monoamine oxidase, Inhibitor binding, Substrate specificity
- MeSH Terms
-
- Animals
- Benzylamines/metabolism
- Binding Sites
- Biocatalysis/drug effects
- Dextroamphetamine/chemistry
- Dextroamphetamine/pharmacology
- Dopamine/metabolism
- Gene Expression
- Humans
- Isoenzymes/genetics
- Isoenzymes/metabolism*
- Kinetics
- Monoamine Oxidase/genetics
- Monoamine Oxidase/metabolism*
- Monoamine Oxidase Inhibitors/chemistry
- Monoamine Oxidase Inhibitors/pharmacology
- Oxidation-Reduction
- Pichia
- Protein Binding
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism*
- Serotonin/metabolism
- Species Specificity
- Substrate Specificity
- Tyramine/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism*
- PubMed
- 21354322 Full text @ Comp. Biochem. Physiol. B Biochem. Mol. Biol.
Citation
Aldeco, M., Arslan, B.K., and Edmondson, D.E. (2011) Catalytic and inhibitor binding properties of zebrafish monoamine oxidase (zMAO): Comparisons with human MAO A and MAO B. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 159(2):78-83.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping