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MetaCyc Enzyme: monoamine oxidase A

Gene: Maoa Accession Number: G-11441 (MetaCyc)

Synonyms: amine oxidase [flavin-containing] A, monoamine oxidase type A, MAO-A

Species: Rattus norvegicus

Subunit composition of monoamine oxidase A = [Maoa]2
         monoamine oxidase A subunit = Maoa

Summary:
Monoamine oxidase activity has a central role in regulating intracellular levels of amines important to the nervous system, including neurotransmitters, trace amines and neurotoxins. Two structurally distinct forms, A and B, exist that share ~70% amino acid sequence identity, but have different substrate and inhibitor specificities. These two enzymes are the major neurotransmitter catabolizing enzymes in both the central nervous system and peripheral tissues. Monoamine oxidase A preferentially oxidizes serotonin and is irreversibly inactivated by clorgyline. In [Ma04a, Tsugeno97] and reviewed in [Abell01].

The rat enzyme has been cloned, expressed in Saccharomyces cerevisiae strain TD-1 cells and characterized by site-directed mutagenesis [Tsugeno97, Ma02a].

The crystal structure of the rat enzyme has been determined. It is thought to form a dimer in vivo [Ma04a].

Gene Citations: [Kuwahara90]

Locations: mitochondrial outer membrane

Map Position: [17,678,536 <- 17,747,006]

Molecular Weight of Polypeptide: 59.508 kD (from nucleotide sequence)

Unification Links: Entrez-gene:29253 , PhosphoSite:P21396 , Pride:P21396 , Protein Model Portal:P21396 , SMR:P21396 , String:P21396 , UniProt:P21396

Relationship Links: InterPro:IN-FAMILY:IPR001613 , InterPro:IN-FAMILY:IPR002937 , InterPro:IN-FAMILY:IPR016040 , PDB:Structure:1O5W , Pfam:IN-FAMILY:PF01593 , Prints:IN-FAMILY:PR00757

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005741 - mitochondrial outer membrane [Schnaitman67]

Credits:
Created 28-Jul-2009 by Fulcher CA , SRI International


Enzymatic reaction of: monoamine oxidase

EC Number: 1.4.3.4

a monoamine + H2O + oxygen <=> an aldehyde + a primary amine + hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.


Enzymatic reaction of: metanephrine oxidase (monoamine oxidase A)

EC Number: 1.4.3.4

metanephrine + H2O + oxygen <=> 3-methoxy-4-hydroxyphenylglycolaldehyde + methylamine + hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: noradrenaline and adrenaline degradation

Summary:
Please see the summary for noradrenaline oxidase activity, below.


Enzymatic reaction of: normetanephrine oxidase (monoamine oxidase A)

EC Number: 1.4.3.4

normetanephrine + H2O + oxygen <=> 3-methoxy-4-hydroxyphenylglycolaldehyde + ammonium + hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: noradrenaline and adrenaline degradation

Summary:
Please see the summary for noradrenaline oxidase activity, below.


Enzymatic reaction of: adrenaline oxidase (monoamine oxidase A)

EC Number: 1.4.3.4

(R)-adrenaline + H2O + oxygen <=> 3,4-dihydroxyphenylglycolaldehyde + methylamine + hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: noradrenaline and adrenaline degradation

Summary:
Please see the summary for noradrenaline oxidase activity, below.


Enzymatic reaction of: noradrenaline oxidase (monoamine oxidase A)

EC Number: 1.4.3.4

(R)-noradrenaline + H2O + oxygen <=> 3,4-dihydroxyphenylglycolaldehyde + ammonium + hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: noradrenaline and adrenaline degradation

Summary:
Rat tracer studies of infused tritiated (R)-noradrenaline, (R)-adrenaline, normetanephrine and metanephrine were performed along with studies of the effects of the monoamine oxidase A inhibitor clorgyline and a monoamine oxidase B inhibitor. Plasma concentrations of metabolites were measured and monoamine oxidases A and B were assayed in samples of liver homogenates. Monoamine oxidasse A activity was assayed using serotonin as substrate [Eisenhofer94].


Enzymatic reaction of: serotonin oxidase (monoamine oxidase A)

EC Number: 1.4.3.4

serotonin + oxygen + H2O <=> 5-hydroxyindole acetaldehyde + ammonium + hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: serotonin degradation


Enzymatic reaction of: tryptamine oxidase (monoamine oxidase A)

EC Number: 1.4.3.4

tryptamine + H2O + oxygen <=> ammonium + indole acetaldehyde + hydrogen peroxide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for tryptamine: tyramine [Tsugeno97 ] , serotonin [Tsugeno97 ] , 2-phenylethylamine [Tsugeno97 ]

In Pathways: tryptophan degradation X (mammalian, via tryptamine)

Cofactors or Prosthetic Groups: FAD [Ma04a]

Inhibitors (Irreversible): clorgyline [Ma04a]

Kinetic Parameters:

Substrate
Km (μM)
Citations
tryptamine
230.0
[Tsugeno97]


References

Abell01: Abell CW, Kwan SW (2001). "Molecular characterization of monoamine oxidases A and B." Prog Nucleic Acid Res Mol Biol 65;129-56. PMID: 11008487

Eisenhofer94: Eisenhofer G, Finberg JP (1994). "Different metabolism of norepinephrine and epinephrine by catechol-O-methyltransferase and monoamine oxidase in rats." J Pharmacol Exp Ther 268(3);1242-51. PMID: 8138937

Kuwahara90: Kuwahara T, Takamoto S, Ito A (1990). "Primary structure of rat monoamine oxidase A deduced from cDNA and its expression in rat tissues." Agric Biol Chem 54(1);253-7. PMID: 1368522

Ma02a: Ma J, Ito A (2002). "Tyrosine residues near the FAD binding site are critical for FAD binding and for the maintenance of the stable and active conformation of rat monoamine oxidase A." J Biochem 131(1);107-11. PMID: 11754741

Ma04a: Ma J, Yoshimura M, Yamashita E, Nakagawa A, Ito A, Tsukihara T (2004). "Structure of rat monoamine oxidase A and its specific recognitions for substrates and inhibitors." J Mol Biol 338(1);103-14. PMID: 15050826

Schnaitman67: Schnaitman C, Erwin VG, Greenawalt JW (1967). "The submitochondrial localization of monoamine oxidase. An enzymatic marker for the outer membrane of rat liver mitochondria." J Cell Biol 32(3);719-35. PMID: 4291912

Tsugeno97: Tsugeno Y, Ito A (1997). "A key amino acid responsible for substrate selectivity of monoamine oxidase A and B." J Biol Chem 272(22);14033-6. PMID: 9162023


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, biocyc12.