Monoamine oxidase
20953
219291586
2008-06-14T14:46:16Z
DOI bot
6652755
Citation maintenance. Initiated by [[User:Fconaway|Fconaway]]. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]].
{{redirect|MAO|other uses|Mao (disambiguation)}}
{{protein
| Name = [[MAOA|monoamine oxidase A]]
| caption = Ribbon diagram of a [[monomer]] of human MAO-A, with [[FAD]] and [[clorgiline]] bound, oriented as if attached to the [[outer membrane]] of a [[mitochondrion]]. From {{PDB|2BXS}}.
| image = Monoamine oxidase A 2BXS.png
| width =
| HGNCid = 6833
| Symbol = [[MAOA]]
| AltSymbols =
| EntrezGene = 4128
| OMIM = 309850
| RefSeq = NM_000240
| UniProt = P21397
| PDB =
| ECnumber = 1.4.3.4
| Chromosome = X
| Arm = p
| Band = 11
| LocusSupplementaryData = .4-p11.3
}}
{{protein
| Name = monoamine oxidase B
| caption = Cartoon diagram of human MAO-B. From {{PDB|1GOS}}.
| image = MonoamineOxidase-1GOS.png
| width =
| HGNCid = 6834
| Symbol = MAOB
| AltSymbols =
| EntrezGene = 4129
| OMIM = 309860
| RefSeq = NM_000898
| UniProt = P27338
| PDB =
| ECnumber = 1.4.3.4
| Chromosome = X
| Arm = p
| Band = 11
| LocusSupplementaryData = .4-p11.3
}}
'''Monoamine oxidases''' (singular abbreviation '''MAO''') ({{EC number|1.4.3.4}}) are [[enzyme]]s that [[catalysis|catalyze]] the [[oxidation]] of [[monoamine]]s. They are found bound to the outer membrane of [[mitochondria]] in most cell types in the body. The enzyme was discovered by Mary Hare in the [[liver]], and received the name of tyramine oxidase.<ref>Hare MLC (1928) Tyramine oxidase. I. A new enzyme system in liver. Biochem J 22:968Y979 </ref> They belong to [[protein family]] of [[flavin containing amine oxidoreductase]]s.
==Locations of MAO-A and MAO-B==
In humans there are two types of MAO: [[Monoamine oxidase A|MAO-A]] and [[MAOB|MAO-B]].
* Both are found in [[neuron]]s and [[astroglia]].
* Outside the [[central nervous system]]:
** MAO-A is also found in the [[liver]], [[gastrointestinal tract]] and [[placenta]].
** MAO-B is mostly found in [[blood]] [[platelet]]s.
==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
[[Image:GabeTheNerd_01_in_2008.png|center|General Form of MAO Oxidations]]
Monoamine [[oxidase]]s contain the covalently-bound [[cofactor (biochemistry)|cofactor]] [[FAD]] and are thus classified as [[flavoprotein]]s.
==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 [[neurotransmitter]]s, for which they display different [[Enzyme#Specificity|specificities]].
* [[Serotonin]], [[norepinephrine]] (noradrenaline), and [[epinephrine]] (adrenaline) are mainly broken down by MAO-A.
* [[Phenethylamine]] is broken down by MAO-B.
* Both forms break down [[dopamine]].
==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 [[clinical depression|depression]], [[substance abuse]], [[attention deficit disorder]], and irregular sexual maturation. [[Monoamine oxidase inhibitor]]s are one of the major classes of drug prescribed for the treatment of depression, although they are last line treatment due to risk of the drug's interaction with diet or other drugs. Excessive levels of [[catecholamine]]s ([[epinephrine]], [[norepinephrine]], and [[dopamine]]) may lead to a hypertensive crisis, and excessive levels of [[serotonin]] may lead to [[serotonin syndrome]].
[[Positron emission tomography|PET]] research has shown that MAO is also heavily depleted by use of [[tobacco]] cigarettes.<ref>{{cite journal |author=Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, MacGregor R, Alexoff D, Wolf AP, Warner D, Cilento R, Zezulkova I |title=Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition. |journal=Journal of addictive diseases |year=1998 |pmid=9549600}}</ref>
==Genetics==
The [[gene]]s encoding MAO-A and MAO-B are located side-by-side on the short arm of the [[X chromosome]], and have about 70% sequence similarity. Rare mutations in the gene are associated with [[Brunner syndrome]].
A study reported in ''[[Science (journal)|Science]]'' in August 2002 based on the [[Dunedin cohort]] concluded that maltreated children with a low-activity polymorphism in the [[promoter]] region of the MAO-A gene were more likely to develop [[conduct disorder|antisocial conduct disorders]] than maltreated children with the high-activity variant.<ref>{{cite journal |author=Caspi A, McClay J, Moffitt T, Mill J, Martin J, Craig I, Taylor A, Poulton R |title=Role of genotype in the cycle of violence in maltreated children |journal=Science |volume=297 |issue=5582 |pages=851–4 |year=2002 |pmid=12161658 | doi = 10.1126/science.1072290 <!--Retrieved from CrossRef by DOI bot-->}}</ref> Out of the 442 total males in the study (maltreated or not), 37% had the low activity variant. Of the 13 maltreated males with low MAO-A activity, 11 had been assessed as exhibiting [[adolescent conduct disorder]] and 4 were convicted for violent offenses. The suggested mechanism for this effect is the decreased ability of those with low MAO-A activity to quickly degrade norepinephrine, the synaptic neurotransmitter involved in [[sympathetic nervous system|sympathetic]] arousal and rage. This is alleged to provide direct support for the idea that genetic susceptibility to disease is not determined at birth, but varies with exposure to environmental influences. Note however that most of those with conduct disorder or convictions did not have low activity of MAO-A; maltreatment was found to caused stronger predisposition for antisocial behavior than differences in MAO-A activity.
Research also uncovered a possible link between predisposition to [[neophilia|novelty seeking]] and a [[genotype]] of the MAO-A gene.<ref>[http://www.medialifemagazine.com/cgi-bin/artman/exec/view.cgi?archive=226&num=5439 The disorder of these times, neophilia], by Heidi Dawley, published June 18, 2006, retrieved on May 22, 2007</ref>
In 2006, a New Zealand researcher, Dr Rod Lea said that a particular variant (or [[genotype]]) was over-represented in [[Māori]], a [[Warrior gene]]. This supported earlier studies finding 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 low-activity MAO-A [[promoter]] variant.<ref>{{cite journal |author=Sabol S, Hu S, Hamer D |title=A functional polymorphism in the monoamine oxidase A gene promoter |journal=Hum Genet |volume=103 |issue=3 |pages=273–9 |year=1998 |pmid=9799080 | doi = 10.1007/s004390050816 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
==See also==
*[[Monoamine oxidase inhibitor]]
*[[Genetics and violence]]
*[[Neophilia]]
*[[Warrior gene]]
*[[Brunner syndrome]]
==References==
{{Reflist|2}}
==External links==
* [http://www.eurekalert.org/pub_releases/2001-11/euhs-sdt_1112101.php MAO-B Structure at eurekalert.org]
* [http://opm.phar.umich.edu/families.php?superfamily=128 Calculated orientations of Monoamine oxidases in membrane]
* [http://alpha2.bmc.uu.se/gerard/research_mao.html Monoamine oxidase (MAO) at bmc.uu.se]
* [http://www.nida.nih.gov/meetsum/nicotine/slides/16Volkow/VolkowSlides.html Slides showing the effects of tobacco smoking on MAO at nida.nih.gov]
*[http://nepenthes.lycaeum.org/Misc/maoi.foods.html Foods to avoid when taking MAO inhibitors at lycaeum.org]
*[http://www.ihop-net.org/UniPub/iHOP/gs/89975.html Information Hyperlinked Over Proteins -- MAO-A]
{{CH-NH2 oxidoreductases}}
{{Mitochondrial enzymes}}
{{Neurotransmitter metabolism enzymes}}
[[Category:EC 1.4.3]]
[[Category:Integral membrane proteins]]
[[de:Monoaminooxidase]]
[[es:Monoamino oxidasa]]
[[fr:Monoamine oxydase]]
[[it:Ammino ossidasi]]
[[he:מונואמין אוקסידאז]]
[[nl:Monoamino-oxidase]]
[[ja:モノアミン酸化酵素]]
[[pl:Monoaminooksydaza]]
[[pt:Monoamina oxidase]]
[[ru:Моноаминоксидаза]]
[[fi:Monoamiinioksidaasi]]