Monoamine oxidase A

Monoamine oxidase A
Ribbon diagram of an MAO-A monomer, with FAD and clorgiline bound, oriented as if attached to the outer membrane of a mitochondrion.[1]
Available structures
2bxr, 2bxs
Identifiers
Symbols	MAOA;
External IDs	OMIM: 309850 MGI: 96915 HomoloGene: 203
EC number	1.4.3.4
Gene ontology Molecular function • amine oxidase activity • oxidoreductase activity Cellular component • mitochondrion • membrane • integral to membrane Biological process • electron transport • catecholamine metabolic process • behavior • dopamine catabolic process
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4128	17161
Ensembl	ENSG00000189221	ENSMUSG00000025037
UniProt	P21397	Q3TPD9
RefSeq	NM_000240 (mRNA)	NM_173740 (mRNA)
	NP_000231 (protein)	NP_776101 (protein)
Location	Chr X: 43.4 - 43.49 Mb	Chr X: 15.78 - 15.84 Mb
PubMed search	[1]	[2]

Monoamine oxidase A, also known as MAOA, is an enzyme which in humans is encoded by the MAOA gene.^[2][3] Monoamine oxidase A is an isozyme of monoamine oxidase. It preferentially deaminates norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin, and dopamine (dopamine is equally deaminated by MAO-A and MAO-B). It is inhibited by clorgiline and befloxatone.

Function

This gene encodes monoamine oxidase A, an enzyme that degrades amine neurotransmitters, such as dopamine, norepinephrine, and serotonin. The protein localizes to the outer mitochondrial membrane. The gene is adjacent to a related gene (MAOB) on the opposite strand of chromosome X. Mutation in this gene results in monoamine oxidase deficiency, or Brunner syndrome.^[4]

Clinical significance

An association between a rare 2 repeat of the VTNR region of the gene and an increase in the likelihood of committing serious crime or violence has been found.^[5][6]

MAO-A levels in the brain as measured using positron emission tomography are elevated by an average of 34 percent in patients with major depressive disorder.^[7] Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females,^[8] depressed suicide in males,^[9] major depression and sleep disturbance in males^[10] and major depressive disorder in both males and females.^[11] Other studies failed to find a significant relationship between high-activity variants of the MAO-A gene and major depressive disorder.^[12][13]

The version of the gene that a person carries may determine or at least significantly influence whether a traumatic childhood experience of violence leads to psychopathy.^[14]

In patients with major depressive disorder, those with MAO-A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme have a significantly lower magnitude of placebo response than those with other genotypes.^[15]

Warrior gene

A version of the primate monoamine oxidase-A gene has been referred to as the warrior gene. Several different versions of the gene are found in different individuals, although a functional gene is present in most humans (with the exception of a few individuals with Brunner syndrome).^[16] The genotype associated with behavioural traits is shorter (30 bases) and may produce less MAO-A enzyme.^[17] This gene variation is in a regulatory promoter region about 1000 bases from the start of the region that encodes the MAO-A enzyme. However, behaviour is dependent on both genes and the environment.^[14]

This variant (or genotype) of monoamine oxidase-A was over-represented in a small sample of current Māori.^[18] This supported earlier studies that there are different proportions of variants in different ethnic groups. This is the case for many genetic variants, with 33% White/Non-Hispanic, 61% Asian/Pacific Islanders having the shorter promoter variant of the MAO-A gene.^[17][19] Due to the sensitive political nature of the findings, and the standard peer review process, the research has been heavily scrutinized. Several objections have been raised, such as the small sample size, and the extrapolation of non-Maori studies to the Maori population. In addition, ideological objections were raised, as well as concerns about announcing such findings in the early stages of research.^{[20][21][22][23]}

Some MAO-A inhibitors

• Synthetic compounds
  • Befloxatone (MD370503)
  • Brofaromine (Consonar)
  • Cimoxatone
  • Clorgiline
  • Methylene Blue
  • Minaprine (Cantor)
  • Moclobemide (Aurox, Manerix)
  • Pirlindole (Pirazidol)
  • Toloxatone (Humoryl)
  • Tyrima (CX 157)
  • Tranylcypromine (non-selective)

• Herbal sources
  • Curcumin (Turmeric)
  • Harmala Alkaloids (Tobacco, Syrian Rue, Passion Flower)
    • Harmine
    • Harmaline
    • Tetrahydroharmaline

See also

• Monoamine oxidase

References

Further reading

v • d • e PDB Gallery 2bxr: HUMAN MONOAMINE OXIDASE A IN COMPLEX WITH CLORGYLINE, CRYSTAL FORM A   2bxs: HUMAN MONOAMINE OXIDASE A IN COMPLEX WITH CLORGYLINE, CRYSTAL FORM B