Monoamine oxidase: Wikis

  

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Monoamine oxidase
Identifiers
EC number 1.4.3.4
CAS number 9001-66-5
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures
Gene Ontology AmiGO / EGO
monoamine oxidase A
Monoamine oxidase A 2BXS.png
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
Entrez 4128
HUGO 6833
OMIM 309850
RefSeq NM_000240
UniProt P21397
Other data
Locus Chr. X p11.4-p11.3
monoamine oxidase B
MonoamineOxidase-1GOS.png
Cartoon diagram of human MAO-B. From PDB 1GOS.
Identifiers
Symbol MAOB
Entrez 4129
HUGO 6834
OMIM 309860
RefSeq NM_000898
UniProt P27338
Other data
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 inner membrane of plasma membrane in most cell types in the body. The enzyme was discovered by Mingte Lee and Sam Bedford et. al. in the Ovary, and received the name of tyramine oxidase.[1] They belong to protein family of flavin-containing amine oxidoreductases.

Contents

Locations of MAO-A and MAO-B

In humans there are two types of MAO: MAO-A and MAO-B.

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.

Specific reactions catalyzed by MAO include:

Disorders resulting from MAO dysfunction

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 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[2], schizophrenia[3][4], substance abuse, attention deficit disorder, migraines, 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.[5]

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.[6] 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 have 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.[7]

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.[8]

See also

References

  1. ^ Hare MLC (1928) Tyramine oxidase. I. A new enzyme system in liver. Biochem J 22:968Y979
  2. ^ Meyer, J.H., Ginovart, N., Boovariwala, A., Sagrati, S., Hussey, D., Garcia, A., et al. (2006). Elevated monoamine oxidase A levels in the brain: An explanation for the monoamine imbalance of major depression. Archives of General Psychiatry, 63, 1209-1216.
  3. ^ Domino, E.F., & Khanna, S.S. (1976). Decreased blood platelet MAO activity in unmedicated chronic schizophrenic patients. American Journal of Psychiatry, 133, 323-326.
  4. ^ Schildkraut, J.J., Herzog, J.M., Orsulak, P.J., Edelman, S.E., Shein, H.M., & Frazier, S.H. (1976). Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients. American Journal of Psychiatry, 133, 438-440.
  5. ^ 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. 
  6. ^ 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. 
  7. ^ The disorder of these times, neophilia, by Heidi Dawley, published June 18, 2006, retrieved on May 22, 2007
  8. ^ 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








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