Monoamine oxidase A

Target id: 2489

Nomenclature: Monoamine oxidase A

Abbreviated Name: MAO-A

Family: Catecholamine turnover

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Monoamine oxidase A in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 527 Xp11.4-p11.3 MAOA monoamine oxidase A
Mouse - 526 X A2 Maoa monoamine oxidase A
Rat - 526 Xq12 Maoa monoamine oxidase A
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 1.4.3.4
Description Reaction Reference
Dopamine -> 3,4-dihydroxyphenylacetaldehyde + NH3
(-)-Noradrenaline -> 3,4-dihydroxymandelic acid + NH3
(-)-Adrenaline -> 3,4-dihydroxymandelic acid + NH3
5-Hydroxytryptamine -> 5-hydroxyindole acetaldehyde + NH3
Tyramine -> 4-hydroxyphenyl acetaldehyde + NH3
Cofactors
Cofactor Species Comments Reference
flavin adenine dinucleotide Human

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
moclobemide Hs Inhibition 8.3 pKi 4
pKi 8.3 (Ki 5x10-9 M) [4]
phenelzine Hs Irreversible inhibition 7.3 pKi 2
pKi 7.3 (Ki 4.7x10-8 M) [2]
selegiline Hs Inhibition 4.2 pKi 6
pKi 4.2 (Ki 6.725x10-5 M) [6]
tranylcypromine Hs Inhibition 4.7 pIC50 8
pIC50 4.7 (IC50 2x10-5 M) [8]
clorgiline Hs Inhibition - -
befloxatone Hs Inhibition - - 3
[3]
pirlindole Hs Inhibition - - 5
[5]
Inhibitor Comments
Differential inhibition of the A or B isozymes of MAO have different clinical outcomes. Inhibition of MAOA results in antidepressant activity [1], whereas inhibition of MAOB results in antiparkinsonian activity [7]. Important substrates for MAO activity in the CNS include dopamine, adrenaline, noradrenaline, serotonin (5-HT), and β-phenylethylamine.
Tranylcypromine is an irreversible MAO inhibitor with equal potency for the A and B isozymes [8].
Clinically-Relevant Mutations and Pathophysiology
Disease:  Brunner syndrome
Synonyms: Monoamine oxidase A deficiency [Orphanet: ORPHA3057]
OMIM: 300615
Orphanet: ORPHA3057

References

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1. Binda C, Hubálek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A. (2004) Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J. Med. Chem.47 (7): 1767-74. [PMID:15027868]

2. Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson DE. (2008) Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry47 (20): 5616-25. [PMID:18426226]

3. Curet O, Damoiseau-Ovens G, Sauvage C, Sontag N, Avenet P, Depoortere H, Caille D, Bergis O, Scatton B. (1998) Preclinical profile of befloxatone, a new reversible MAO-A inhibitor. J Affect Disord51 (3): 287-303. [PMID:10333983]

4. Jagrat M, Behera J, Yabanoglu S, Ercan A, Ucar G, Sinha BN, Sankaran V, Basu A, Jayaprakash V. (2011) Pyrazoline based MAO inhibitors: synthesis, biological evaluation and SAR studies. Bioorg. Med. Chem. Lett.21 (14): 4296-300. [PMID:21680183]

5. Medvedev AE, Shvedov VI, Chulkova TM, Fedotova OA, Saederup E, Squires RF. (1998) The influence of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase A and GABAA receptor binding. J. Neural Transm. Suppl.52: 337-42. [PMID:9564636]

6. Mishra N, Sasmal D. (2011) Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation. Bioorg. Med. Chem. Lett.21 (7): 1969-73. [PMID:21377879]

7. Tetrud JW, Langston JW. (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science245 (4917): 519-22. [PMID:2502843]

8. Yoshida S, Rosen TC, Meyer OG, Sloan MJ, Ye S, Haufe G, Kirk KL. (2004) Fluorinated phenylcyclopropylamines. Part 3: Inhibition of monoamine oxidase A and B. Bioorg. Med. Chem.12 (10): 2645-52. [PMID:15110846]

How to cite this page

Catecholamine turnover: Monoamine oxidase A. Last modified on 16/04/2015. Accessed on 23/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2489.