Monoamine oxidase
From Wikipedia, the free encyclopedia
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monoamine oxidase A
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| Identifiers | |
| Symbol(s) | MAOA |
| Entrez | 4128 |
| OMIM | 309850 |
| RefSeq | NM_000240 |
| UniProt | P21397 |
| Other data | |
| EC number | 1.4.3.4 |
| Locus | Chr. X p11.4-p11.3 |
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monoamine oxidase B
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| Identifiers | |
| Symbol(s) | MAOB |
| Entrez | 4129 |
| OMIM | 309860 |
| RefSeq | NM_000898 |
| UniProt | P27338 |
| Other data | |
| EC number | 1.4.3.4 |
| Locus | Chr. X p11.4-p11.3 |
Monoamine oxidases (singular abbreviation MAO) (EC 1.4.3.4) are enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body.
In humans there are two types of MAO: MAO-A and MAO-B. Both are found in neurons and astroglia; MAO-A is also found in the liver, gastrointestinal tract and placenta. Outside the central nervous system, MAO-B is mostly found in blood platelets.
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[edit] Function
Monoamine oxidases catalyze the oxidative deamination of monoamines. Oxygen is used to remove an amine group from a molecule, resulting in the corresponding aldehyde and ammonia. The general form of the catalyzed reaction (with R denoting an arbitrary group) is
H H
R-C-NH2 + O2 + H2O → R-C=O + NH3 + H2O2
H
Monoamine oxidase contains the covalently-bound cofactor FAD.
[edit] Subtype Specificities
MAO-A is particularly important in the catabolism of monoamines ingested in food. Both MAOs are also vital to the inactivation of monoaminergic neurotransmitters, for which they display different specificities. Thus, serotonin is mainly broken down by MAO-A, as is norepinephrine (noradrenaline) and epinephrine (adrenaline), while phenethylamine is broken down by MAO-B. Both forms break down dopamine.
[edit] Disorders resulting from MAO dysfunction
Because of the vital role that MAOs play in the inactivation of neurotransmitters, MAO dysfunction (too much/too little MAO activity) is thought to be responsible for a number of neurological disorders. For example, unusually high or low levels of MAOs in the body have been associated with depression, substance abuse, criminality, attention deficit disorder, and social phobias. Monoamine oxidase inhibitors are one of the major classes of drug prescribed for the treatment of depression.
Recent PET research has shown that MAO is also heavily depleted by tobacco use.
[edit] Genetics
The promoters and genes encoding MAO-A and MAO-B are all located on the short arm of the X chromosome. The two encoding genes are to be found side-by-side, and have about 70% similarity.
A study reported in Science in August 2002 concluded that maltreated children with a low-activity MAO-A promoter were more likely to develop antisocial conduct disorders than maltreated children with high-activity promoters. The suggested mechanism for this effect is the decreased ability of those with low-activity promoters to quickly degrade norepinephrine, the synaptic neurotransmitter involved in sympathetic arousal and rage. [1] This is alleged to provide direct support for the idea that 'promoter genes' are mechanisms by which experience influences us.
Research also uncovered a possible link between predisposition to novelty seeking and a genotype of the MAO-A gene. [2]
An American group studying monkeys called MAO-A a "warrior gene" in 2004.[3]. In 2006, a New Zealand researcher, Dr Rod Lea said that a particular variant (or genotype) was over-represented in Māori. 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 weaker MAO-A promoter. [4]. Note that the promoter is in the regulatory region about 1000 bases from the start of the MAO-A coding gene.
The reported suggestion that a single 'gene' alone, in this case the MAO-A promoter gene, can cause any complex behavior has been refuted by Nobel Prize winner Paul Nurse [5] (NZ Herald)
[edit] Reference
- Caspi, A. Moffitt, T.E. et al. 2002. Role of genotype in the cycle of violence in maltreated children. Science 297 (Aug. 2):851-854. PMID 12161658
