monoamine oxidase

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 Search PMC articles PubMed articles

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 Entrez 4128 HUGO 6833 OMIM 309850 RefSeq NM_000240 UniProt P21397 Other data Locus Chr. X p11.4-p11.3

monoamine oxidase B 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 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.

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:

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 mainly broken down by MAO-B.
• Both forms break down dopamine equally.

Specific reactions catalyzed by MAO include:

• epinephrine or norepinephrine to 3,4-Dihydroxymandelic acid
• metanephrine or normetanephrine to vanillylmandelic acid (VMA)
• dopamine to dihydroxyphenylacetic acid
• 3-Methoxytyramine to homovanillic acid

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 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

• Monoamine oxidase inhibitor
• Genetics and violence
• Neophilia
• Warrior gene
• Brunner syndrome

References

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