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07-SEPTEMBER-2008 03:17:44 - oxidase MAO redirects here. For other uses, see Mao disambiguation. 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. monoamine oxidase A Identifiers Symbol MAOA Entrez 4128 HUGO 6833 OMIM 309850 RefSeq NM_000240 UniProt P21397 Other data EC number 1.4.3.4 Locus Chr. X p11.4-p11.3 Cartoon diagram of human MAO-B. From PDB 1GOS. monoamine oxidase B Identifiers Symbol MAOB Entrez 4129 HUGO 6834 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. The enzyme was discovered by Mary Hare in the liver, and received the name of tyramine oxidase.1 They belong to protein family of flavin containing amine oxidoreductases. Contents 1 Locations of MAO-A and MAO-B 2 Function 3 Subtype Specificities 4 Disorders resulting from MAO dysfunction 5 Genetics 6 See also 7 References 8 External links Locations of MAO-A and MAO-B In humans there are two types of MAO: MAO-A and MAO-B. Both are found in neurons 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 platelets. 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 General Form of MAO Oxidations Monoamine oxidases contain the covalently-bound cofactor FAD and are thus classified as flavoproteins. 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. 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 depression, substance abuse, attention deficit disorder, and irregular sexual maturation. Monoamine oxidase inhibitors 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 catecholamines epinephrine, norepinephrine, and dopamine may lead to a hypertensive crisis, and excessive levels of serotonin may lead to serotonin syndrome. PET research has shown that MAO is also heavily depleted by use of tobacco cigarettes.2 Genetics The genes 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 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 antisocial conduct disorders than maltreated children with the high-activity variant.3 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 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 novelty seeking and a genotype of the MAO-A gene.4 In 2006, a New Zealand researcher, Dr Rod Lea said that a particular variant or genotype was over-represented in MÄ?ori, 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.5 See also Monoamine oxidase inhibitor Genetics and violence Neophilia Warrior gene Brunner syndrome References ^ Hare MLC 1928 Tyramine oxidase. I. A new enzyme system in liver. Biochem J 22:968Y979 ^ Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, MacGregor R, Alexoff D, Wolf AP, Warner D, Cilento R, Zezulkova I 1998. Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B MAO B inhibition. Journal of addictive diseases. PMID 9549600. ^ Caspi A, McClay J, Moffitt T, Mill J, Martin J, Craig I, Taylor A, Poulton R 2002. Role of genotype in the cycle of violence in maltreated children. Science 297 5582: 851-4. doi:10.1126/science.1072290. PMID 12161658. ^ The disorder of these times, neophilia, by Heidi Dawley, published June 18, 2006, retrieved on May 22, 2007 ^ Sabol S, Hu S, Hamer D 1998. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103 3: 273-9. doi:10.1007/s004390050816. PMID 9799080. External links MAO-B Structure at eurekalert.org Calculated orientations of Monoamine oxidases in membrane Monoamine oxidase MAO at bmc.uu.se Slides showing the effects of tobacco smoking on MAO at nida.nih.gov Foods to avoid when taking MAO inhibitors at lycaeum.org Information Hyperlinked Over Proteins -- MAO-A v d e CH-NH2 oxidoreductases EC 1.4 - primarily amino acid oxidoreductases 1.4.1 - NAD/NADP acceptor Glutamate dehydrogenase GLUD1 1.4.3 - oxygen acceptor D-amino acid oxidase - Amine oxidase - Lysyl oxidase - Monoamine oxidase 1.4.4 - disulfide acceptor Glycine decarboxylase complex 1.4.99 - other acceptors D-amino acid dehydrogenase - Amine dehydrogenase v d e Mitochondrial enzymes and transporters Outer membrane fatty acid degradation Carnitine palmitoyltransferase I, Long fatty acyl CoA synthetase tryptophan metabolism Kynureninase monoamine neurotransmitter metabolism Monoamine oxidase Intermembrane space Adenylate kinase - Creatine kinase Inner membrane oxidative phosphorylation Coenzyme Q - cytochrome c reductase, Cytochrome c, NADH dehydrogenase, Succinate dehydrogenase pyrimidine metabolism Dihydroorotate dehydrogenase mitochondrial shuttle Malate-aspartate shuttle, Glycerol phosphate shuttle other Glutamate aspartate transporter, Glycerol-3-phosphate dehydrogenase, ATP synthase, Carnitine palmitoyltransferase II Matrix citric acid cycle Citrate synthase, Aconitase, Isocitrate dehydrogenase, Oxoglutarate dehydrogenase, Succinyl coenzyme A synthetase, Fumarase, Malate dehydrogenase anaplerotic reactions Aspartate transaminase, Glutamate dehydrogenase, Pyruvate dehydrogenase complex urea cycle Carbamoyl phosphate synthetase I, Ornithine transcarbamylase, N-Acetylglutamate synthase alcohol metabolism ALDH2 Other/to be sorted Cholesterol side-chain cleavage enzyme Mitochondrial DNA Complex I 7 units - Complex III 1 unit - Complex IV 3 units - ATP synthase 2 units v d e Metabolism: amino acid metabolism - neurotransmitter enzymes histidine→histamine anabolism: Histidine decarboxylase catabolism: Histamine N-methyltransferase - Amine oxidase tyrosine→dopamine→epinephrine anabolism: Tyrosine hydroxylase - Aromatic L-amino acid decarboxylase - Dopamine beta hydroxylase - Phenylethanolamine N-methyltransferase catabolism: Catechol-O-methyl transferase - Monoamine oxidase glutamate→GABA anabolism: Glutamate decarboxylase catabolism: 4-aminobutyrate aminotransferase - 4-aminobutyrate transaminase tryptophan→serotonin→melatonin Tryptophan hydroxylase - Aromatic L-amino acid decarboxylase - Acetylserotonin O-methyltransferase arginine→NO Nitric oxide synthase NOS1, NOS2A, NOS3 choline→Acetylcholine anabolism: Choline acetyltransferase catabolism: Cholinesterase Acetylcholinesterase, Butyrylcholinesterase see also intermediates Retrieved from http://en..org/wiki/Monoamine_oxidase Categories: Genes on chromosome X | EC 1.4.3 | Integral membrane proteins Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Español Français Italiano עברית Nederlands 日本語 Polski Português РуÑ?Ñ?кий Suomi This page was last modified on 13 August 2008, at 19:10
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