Monoamine oxidase
Monoamine oxidase | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
EC no. | 1.4.3.4 | ||||||||
CAS no. | 9001-66-5 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
|
Monoamine oxidase | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | MAO | ||||||||
Pfam | PF01593 | ||||||||
InterPro | IPR001613 | ||||||||
OPM superfamily | 119 | ||||||||
OPM protein | 2z5x | ||||||||
Membranome | 418 | ||||||||
|
monoamine oxidase A | |||||||
---|---|---|---|---|---|---|---|
![]() 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. | |||||||
Identifiers | |||||||
Symbol | MAOA | ||||||
NCBI gene | 4128 | ||||||
HGNC | 6833 | ||||||
OMIM | 309850 | ||||||
RefSeq | NM_000240 | ||||||
UniProt | P21397 | ||||||
Other data | |||||||
Locus | Chr. X p11.4-p11.3 | ||||||
|
monoamine oxidase B | |||||||
---|---|---|---|---|---|---|---|
![]() | |||||||
Identifiers | |||||||
Symbol | MAOB | ||||||
NCBI gene | 4129 | ||||||
HGNC | 6834 | ||||||
OMIM | 309860 | ||||||
RefSeq | NM_000898 | ||||||
UniProt | P27338 | ||||||
Other data | |||||||
Locus | Chr. X p11.4-p11.3 | ||||||
|
Monoamine oxidases (MAO) (EC 1.4.3.4) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group.[1][2] They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase.[3][4] The MAOs belong to the protein family of flavin-containing amine oxidoreductases.[5]
MAOs are important in the breakdown of monoamines ingested in food, and also serve to inactivate monoamine neurotransmitters. Because of the latter, they are involved in a number of psychiatric and neurological diseases, some of which can be treated with monoamine oxidase inhibitors (MAOIs) which block the action of MAOs.[6]
Subtypes and tissue distribution
[edit]In humans there are two types of MAO: MAO-A and MAO-B.[7]
- Both are found in neurons and astroglia.
- Outside the central nervous system:
- MAO-A is also found in the liver, pulmonary vascular endothelium, gastrointestinal tract, and placenta.
- MAO-B is mostly found in blood platelets.
MAO-A appears at roughly 80% of adulthood levels at birth, increasing very slightly after the first 4 years of life, while MAO-B is almost non-detectable in the infant brain. Regional distribution of the monoamine oxidases is characterized by extremely high levels of both MAOs in the hypothalamus and hippocampal uncus, as well as a large amount of MAO-B with very little MAO-A in the striatum and globus pallidus. The cortex has relatively high levels of only MAO-A, with the exception of areas of the cingulate cortex, which contains a balance of both. Autopsied brains demonstrated the predicted increased concentration of MAO-A in regions dense in serotonergic neurotransmission, however MAO-B only correlated with norepinephrine.[8]
Other studies, in which the activities of MAO (not protein amounts) were examined in rat brain, revealed the highest MAO-B activity in the median eminence of hypothalamus. Dorsal raphe nucleus and medial preoptic area have relatively high MAO-B activity, but much lower than MAO-B activity in the median eminence.[9][10] Among cerebral endocrine glands, pineal gland has high MAO-B activity (its median value is lower than that for median eminence and higher than that for medial preoptic area).[10] Pituitary has the lowest level of MAO-B activity when compared with brain areas studied.[9]
Function
[edit]![](http://upload.wikimedia.org/wikipedia/commons/thumb/b/bd/Noradrenaline_breakdown.svg/350px-Noradrenaline_breakdown.svg.png)
Monoamine oxidases catalyze the oxidative deamination of monoamines. In the first part of the reaction, cofactor FAD oxidizes the substrate yielding the corresponding imine which converts the cofactor into its reduced form FADH2. The imine is then non-enzymatically hydrolyzed to the corresponding ketone (or aldehyde) and ammonia. Oxygen is used to restore the reduced FADH2 cofactor back to the active FAD form. Monoamine oxidases contain the covalently bound cofactor FAD and are, thus, classified as flavoproteins. Monoamine oxidase A and B share roughly 70% of their structure and both have substrate binding sites that are predominantly hydrophobic. Two tyrosine residues (398, 435 within MAO-B, 407 and 444 within MAO-A) in the binding pocket that are commonly involved in inhibitor activity have been hypothesized to be relevant to orienting substrates, and mutations of these residues are relevant to mental health. Four main models have been proposed for the mechanism of electron transfer (single electron transfer, hydrogen atom transfer, nucleophilic model, and hydride transfer[12]) although there is insufficient evidence to support any of them.[13]
Substrate specificities
[edit]Monoamine oxidases are well known enzymes in pharmacology, since they are the target for the action of a number of monoamine oxidase inhibitor drugs. MAO-A is particularly important in the catabolism of monoamines ingested in food. Both MAOs are also vital to the inactivation of monoamine neurotransmitters, for which they display different specificities.[medical citation needed]
- Serotonin, melatonin, norepinephrine, and epinephrine are mainly broken down by MAO-A.[medical citation needed]
- Phenethylamine and benzylamine are mainly broken down by MAO-B.[medical citation needed]
- Both forms metabolize dopamine, tyramine, and tryptamine;[14] however, some evidence suggests MAO-B may not be responsible for a significant amount of dopamine degradation.[15]
Specific reactions catalyzed by MAO include:
- Adrenaline or noradrenaline to 3,4-Dihydroxymandelic acid;[medical citation needed]
- Metanephrine or normetanephrine to vanillylmandelic acid (VMA);[medical citation needed]
- Dopamine to dihydroxyphenylacetic acid;[medical citation needed]
- 3-Methoxytyramine to homovanillic acid.[medical citation needed]
Clinical significance
[edit]Because of the vital role that MAOs play in the inactivation of neurotransmitters, MAO dysfunction (too much or too little MAO activity) is thought to contribute to a number of psychiatric and neurological disorders. Unusually high or low levels of MAOs in the body have been associated with schizophrenia,[16][17] depression,[18] attention deficit disorder,[19] substance abuse,[20] migraines,[21][22] and irregular sexual maturation.[citation needed] Monoamine oxidase inhibitors are one of the major classes of drug prescribed for the treatment of depression, although they are often 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.[medical citation needed]
In fact, MAO-A inhibitors act as antidepressant and anti-anxiety agents, whereas MAO-B inhibitors are used alone or in combination to treat Alzheimer's disease and Parkinson's disease.[23] Some research suggests that certain phenotypes of depression, such as those with anxiety, and "atypical" symptoms involving psychomotor retardation, weight gain and interpersonal sensitivity respond better to MAO inhibitors than other classes of anti-depressant. However the findings related to this have not been consistent.[24] MAOIs may be effective in treatment resistant depression, especially when it does not respond to tricyclic antidepressants.[25]
Parasite interactions
[edit]Sleeping sickness - caused by trypanosomes - gets its name from the sleep disruption it causes in mammals. That sleep disruption is caused, at least in part, by trypanosomes' tendency to disrupt MAO activity in the orexin system.[26]
Animal models
[edit]There are significant differences in MAO activity in different species. Dopamine is primarily deaminated by MAO-A in rats, but by MAO-B in vervet monkeys and humans.[27]
Mice unable to produce either MAO-A or MAO-B display autistic-like traits.[28] These knockout mice display an increased response to stress.[29]
Arthropods
[edit]Insects
[edit]Insect brains express MAOs,[30][31][32] and some insecticides[33][32] work by inhibiting them. An MAOI effect is especially important for chlordimeform[33][32][34] (although one result shows little or no effect in Periplaneta americana);[35] and dieldrin may[30] or may not[31] be an MAOI in Locusta migratoria.[medical citation needed]
Acari
[edit]MAO activity has been detected in Rhipicephalus microplus and chlordimeform is an MAOI in R. m..[36]
Genetics
[edit]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.[medical citation needed]
A study 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.[37] 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 argued to provide direct support for the idea that genetic susceptibility to disease is not determined at birth, but varies with exposure to environmental influences. However, most individuals with conduct disorder or convictions did not have low activity of MAO-A; maltreatment was found to have caused stronger predisposition for antisocial behavior than differences in MAO-A activity.[medical citation needed]
The claim that an interaction between low MAO-A activity and maltreatment would cause anti-social behavior has been criticized since the predisposition towards anti-social behavior could equally well have been caused by other genes inherited from abusive parents.[38]
A possible link between predisposition to novelty seeking and a genotype of the MAO-A gene has been found.[39]
A particular variant (or genotype), dubbed "warrior gene" in the popular press, was over-represented in Māori. 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.[40]
Aging
[edit]Unlike many other enzymes, MAO-B activity is increased during aging in the brain of humans and other mammals.[41] Increased MAO-B activity was also found in the pineal gland of aging rats.[10] This may contribute to lowered levels of monoamines in aged brain and pineal gland.[10][42]
See also
[edit]References
[edit]- ^ Tipton KF, Boyce S, O'Sullivan J, Davey GP, Healy J (August 2004). "Monoamine oxidases: certainties and uncertainties". Current Medicinal Chemistry. 11 (15): 1965–82. doi:10.2174/0929867043364810 (inactive 2024-04-05). PMID 15279561.
{{cite journal}}
: CS1 maint: DOI inactive as of April 2024 (link) - ^ Edmondson DE, Mattevi A, Binda C, Li M, Hubálek F (August 2004). "Structure and mechanism of monoamine oxidase". Current Medicinal Chemistry. 11 (15): 1983–93. doi:10.2174/0929867043364784 (inactive 2024-04-05). PMID 15279562.
{{cite journal}}
: CS1 maint: DOI inactive as of April 2024 (link) - ^ Hare ML (1928). "Tyramine oxidase: A new enzyme system in liver". The Biochemical Journal. 22 (4): 968–79. doi:10.1042/bj0220968. PMC 1252213. PMID 16744124.
- ^ Slotkin TA (1999). "Mary Bernheim and the discovery of monoamine oxidase". Brain Research Bulletin. 50 (5–6): 373. doi:10.1016/S0361-9230(99)00110-0. PMID 10643441. S2CID 35565156.
- ^ "CDD Conserved Protein Domain Family: Amino_oxidase".
- ^ Yeung AW, Georgieva MG, Atanasov AG, Tzvetkov NT (2019). "Monoamine Oxidases (MAOs) as Privileged Molecular Targets in Neuroscience: Research Literature Analysis". Frontiers in Molecular Neuroscience. 12: 143. doi:10.3389/fnmol.2019.00143. PMC 6549493. PMID 31191248.
- ^ Shih JC, Chen K (August 2004). "Regulation of MAO-A and MAO-B gene expression". Current Medicinal Chemistry. 11 (15): 1995–2005. doi:10.2174/0929867043364757. PMID 15279563.
- ^ Tong J, Meyer JH, Furukawa Y, Boileau I, Chang LJ, Wilson AA, et al. (June 2013). "Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies". Journal of Cerebral Blood Flow and Metabolism. 33 (6): 863–71. doi:10.1038/jcbfm.2013.19. PMC 3677103. PMID 23403377.
- ^ a b Razygraev AV, Arutjunyan AV (2007-09-01). "Monoamine oxidase activity in several structures of rat brain". Neurochemical Journal. 1 (3): 204–207. doi:10.1134/S1819712407030051. S2CID 9550341.
- ^ a b c d Razygraev AV, Taborskaya KI, Volovik KY, Bunina AA, Petrosyan MA (2016-04-01). "Monoamine oxidase activity in the rat pineal gland: Comparison with brain areas and alteration during aging". Advances in Gerontology. 6 (2): 111–116. doi:10.1134/S2079057016020120. S2CID 88975594.
- ^ Figure 11-4 in: Flower R, Rang HP, Dale MM, Ritter JM (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-06911-6.
- ^ Vianello R, Repič M, Mavri J (2012-10-25). "How are Biogenic Amines Metabolized by Monoamine Oxidases?". European Journal of Organic Chemistry. 2012 (36): 7057–7065. doi:10.1002/ejoc.201201122.
- ^ Gaweska H, Fitzpatrick PF (October 2011). "Structures and Mechanism of the Monoamine Oxidase Family". Biomolecular Concepts. 2 (5): 365–377. doi:10.1515/BMC.2011.030. PMC 3197729. PMID 22022344.
- ^ Kalgutkar AS, Dalvie DK, Castagnoli N, Taylor TJ (September 2001). "Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrates and inhibitors". Chemical Research in Toxicology. 14 (9): 1139–62. doi:10.1021/tx010073b. PMID 11559028.
- ^ Cho HU, Kim S, Sim J, Yang S, An H, Nam MH, et al. (July 2021). "Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis". Exp Mol Med. 53 (7): 1148–1158. doi:10.1038/s12276-021-00646-3. PMC 8333267. PMID 34244591.
- ^ Domino EF, Khanna SS (March 1976). "Decreased blood platelet MAO activity in unmedicated chronic schizophrenic patients". The American Journal of Psychiatry. 133 (3): 323–6. doi:10.1176/ajp.133.3.323. PMID 943955.
- ^ Schildkraut JJ, Herzog JM, Orsulak PJ, Edelman SE, Shein HM, Frazier SH (April 1976). "Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients". The American Journal of Psychiatry. 133 (4): 438–40. doi:10.1176/ajp.133.4.438. PMID 1267046.
- ^ Meyer JH, Ginovart N, Boovariwala A, Sagrati S, Hussey D, Garcia A, et al. (November 2006). "Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression". Archives of General Psychiatry. 63 (11): 1209–16. doi:10.1001/archpsyc.63.11.1209. PMID 17088501.
- ^ Domschke K, Sheehan K, Lowe N, Kirley A, Mullins C, O'sullivan R, et al. (April 2005). "Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 134B (1): 110–4. doi:10.1002/ajmg.b.30158. PMID 15717295. S2CID 24453719.
- ^ Oreland L (January 2004). "Platelet monoamine oxidase, personality and alcoholism: the rise, fall and resurrection". Neurotoxicology. 25 (1–2): 79–89. Bibcode:2004NeuTx..25...79O. doi:10.1016/S0161-813X(03)00115-3. PMID 14697883.
- ^ Bussone G, Boiardi A, Cerrati A, Girotti F, Merati B, Rivolta G (1 October 2016). "Monoamine oxidase activities in patients with migraine or with cluster headache during the acute phases and after treatment with L-5-hydroxytryptophan". Rivista di Patologia Nervosa e Mentale. 100 (5): 269–74. PMID 318025.
- ^ Filic V, Vladic A, Stefulj J, Cicin-Sain L, Balija M, Sucic Z, et al. (February 2005). "Monoamine oxidases A and B gene polymorphisms in migraine patients". Journal of the Neurological Sciences. 228 (2): 149–53. doi:10.1016/j.jns.2004.11.045. PMID 15694196. S2CID 572208.
- ^ Riederer P, Lachenmayer L, Laux G (August 2004). "Clinical applications of MAO-inhibitors". Current Medicinal Chemistry. 11 (15): 2033–43. doi:10.2174/0929867043364775 (inactive 2024-04-05). PMID 15279566.
{{cite journal}}
: CS1 maint: DOI inactive as of April 2024 (link) - ^ Maj M, Stein DJ, Parker G, Zimmerman M, Fava GA, De Hert M, et al. (October 2020). "The clinical characterization of the adult patient with depression aimed at personalization of management". World Psychiatry. 19 (3): 269–293. doi:10.1002/wps.20771. PMC 7491646. PMID 32931110.
- ^ Fiedorowicz JG, Swartz KL (July 2004). "The role of monoamine oxidase inhibitors in current psychiatric practice". Journal of Psychiatric Practice. 10 (4): 239–48. doi:10.1097/00131746-200407000-00005. PMC 2075358. PMID 15552546.
- ^ Kristensson K, Nygård M, Bertini G, Bentivoglio M (June 2010). "African trypanosome infections of the nervous system: parasite entry and effects on sleep and synaptic functions". Progress in Neurobiology. 91 (2): 152–71. doi:10.1016/j.pneurobio.2009.12.001. PMID 19995590. S2CID 207406469.
- ^ Garrick NA, Murphy DL (1980). "Species differences in the deamination of dopamine and other substrates for monoamine oxidase in brain". Psychopharmacology. 72 (1): 27–33. doi:10.1007/bf00433804. PMID 6781004. S2CID 30722852.
- ^ Bortolato M, Godar SC, Alzghoul L, Zhang J, Darling RD, Simpson KL, et al. (May 2013). "Monoamine oxidase A and A/B knockout mice display autistic-like features". The International Journal of Neuropsychopharmacology. 16 (4): 869–88. doi:10.1017/S1461145712000715. PMC 3517692. PMID 22850464.
- ^ Shih JC (January 2004). "Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B". Neurotoxicology. 25 (1–2): 21–30. Bibcode:2004NeuTx..25...21S. doi:10.1016/s0161-813x(03)00112-8. PMID 14697877.
- ^ a b Gripois D, Moreteau B, Ramade F (March 1977). "Sur l'activité monoaminoxydasique du cerveau de Locusta migratoria dans les conditions normales et après intoxication par deux insecticides: le chlordiméform et la diéldrine" [Monoamine oxidase activity of the brain of Locusta migratoria in normal conditions and after intoxication by two insecticides: chlordimeform and dieldrin]. Comptes Rendus de l'Académie des Sciences, Série D. 284 (12): 1079–82. PMID 406057. S2CID 29861405.
- ^ a b Evans PD (1980). "Biogenic Amines in the Insect Nervous System". Advances in Insect Physiology. Vol. 15. pp. 317–473. doi:10.1016/s0065-2806(08)60143-5. ISBN 978-0-12-024215-3. ISSN 0065-2806. S2CID 83010475.
- ^ a b c Lund AE, Hollingworth RM, Shankland DL (1979). "Chlordimeform: Plant protection by a sublethal, noncholinergic action on the central nervous system". Pesticide Biochemistry and Physiology. 11 (1–3): 117–128. Bibcode:1979PBioP..11..117L. doi:10.1016/0048-3575(79)90052-x. ISSN 0048-3575.
- ^ a b Aziz SA, Knowles CO (April 1973). "Inhibition of monoamine oxidase by the pesticide chlordimeform and related compounds". Nature. 242 (5397): 417–8. Bibcode:1973Natur.242..417A. doi:10.1038/242417a0. PMID 4701207. S2CID 4162760.
- ^ Beeman RW, Matsumura F (1974). "Studies on the action of chlordimeform in cockroaches". Pesticide Biochemistry and Physiology. 4 (3): 325–336. Bibcode:1974PBioP...4..325B. doi:10.1016/0048-3575(74)90115-1. ISSN 0048-3575. S2CID 83944360.
- ^ Sloley BD, Bailey BA, Downer RG (1985). "Effects of chlordimeform and lindane on monoamine levels in the central nervous system of the american cockroach, Periplaneta americana L.". Pesticide Biochemistry and Physiology. 24 (2): 213–219. Bibcode:1985PBioP..24..213S. doi:10.1016/0048-3575(85)90131-2. ISSN 0048-3575. S2CID 84947221.
- ^ P. Atkinson, K. Binnington, W. J. Roulston (1974). "High monoamine oxidase activity in the tick Boophilus Microplus and inhibition by chlordimeform and related pesticides". Australian Journal of Entomology. 13 (3): 207–210. doi:10.1111/j.1440-6055.1974.tb02174.x. S2CID 83731654.
- ^ Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, et al. (August 2002). "Role of genotype in the cycle of violence in maltreated children". Science. 297 (5582): 851–4. Bibcode:2002Sci...297..851C. doi:10.1126/science.1072290. PMID 12161658. S2CID 7882492.
- ^ Sesardic N (2005). Making sense of heritability. Cambridge, UK: Cambridge University Press. ISBN 978-0-521-82818-5.
- ^ Shiraishi H, Suzuki A, Fukasawa T, Aoshima T, Ujiie Y, Ishii G, et al. (April 2006). "Monoamine oxidase A gene promoter polymorphism affects novelty seeking and reward dependence in healthy study participants". Psychiatric Genetics. 16 (2): 55–8. doi:10.1097/01.ypg.0000199447.62044.ef. PMID 16538181. S2CID 25418973.
- Heidi Dawley (June 18, 2006). "The disorder of these times, neophilia". Media Life. Archived from the original on 2007-09-30.
- ^ Sabol SZ, Hu S, Hamer D (September 1998). "A functional polymorphism in the monoamine oxidase A gene promoter". Human Genetics. 103 (3): 273–9. doi:10.1007/s004390050816. PMID 9799080. S2CID 29954052. Archived from the original on 2021-04-04. Retrieved 2021-03-30.
- ^ Nicotra A, Pierucci F, Parvez H, Senatori O (January 2004). "Monoamine oxidase expression during development and aging". Neurotoxicology. 25 (1–2): 155–65. Bibcode:2004NeuTx..25..155N. doi:10.1016/S0161-813X(03)00095-0. PMID 14697890.
- ^ Razygraev AV, Arutiunian AV (2008). "[Pineal gland and brain structures monoamine oxidase activity in rats of different age]". Advances in Gerontology = Uspekhi Gerontologii (in Russian). 21 (3): 402–5. PMID 19432173.