Monoamine oxidases (MAO) () are a family of enzyme
s that catalyze
s, employing oxygen to clip off their amine group.
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.
The MAOs belong to the protein family
of flavin-containing amine oxidoreductase
MAOs are important in the breakdown of monoamines ingested in food, and also serve to inactivate monoamine neurotransmitter
s. 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.
Subtypes and tissue distribution
In humans there are two types of MAO: MAO-A
* Both are found in neuron
s 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 platelet
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.
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.
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).
Pituitary has the lowest level of MAO-B activity when compared with brain areas studied.
Monoamine oxidases catalyze the oxidative deamination
of monoamines. Oxygen
is used to remove an amine
group (plus the adjacent hydrogen atom) from a molecule, resulting in the corresponding ketone
) and ammonia
. Monoamine oxidase
s contain the covalently bound cofactor FAD
and are, thus, classified as flavoprotein
s. 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, 407 and 444) 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) although there is insufficient evidence to support any of them.
They are well known enzymes
, 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 neurotransmitter
s, for which they display different specificities
, and epinephrine
are mainly broken down by MAO-A.
are mainly broken down by MAO-B.
* Both forms break down dopamine
, and tryptamine
Specific reactions catalyzed by MAO include:
to 3,4-Dihydroxymandelic acid
to vanillylmandelic acid (VMA)
to dihydroxyphenylacetic acid
to homovanillic acid
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 psychiatric and neurological disorders. For example, unusually high or low levels of MAOs in the body have been associated with schizophrenia
attention deficit disorder
, substance abuse
, migraines, 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 often last-line treatment due to risk of the drug's interaction with diet or other drugs. Excessive levels of catecholamine
, and dopamine
) may lead to a hypertensive crisis
, and excessive levels of serotonin
may lead to serotonin syndrome
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
Some research suggests that certain phenotypes of depression, such as those with anxiety, and "atypical" symptoms involving psychomotor retardation, weight gain and interpersonal sensitivity. However the findings related to this have not been consistent. MAOIs may be effective in treatment resistant depression, especially those that do not respond to tricyclic antidepressants.
research shows that use of tobacco
cigarettes heavily depletes MAO-B, mimicking the action of an MAO-B inhibitor. Smokers who smoke for emotional relief may therefore be unintentionally treating depression and/or anxiety that is better addressed by an MAO-B inhibitor.
- 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
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 monkey
s and humans.
Mice unable to produce either MAO-A or MAO-B display autistic-like
These knockout mice
display an increased response to stress.
Insect brains express MAOs,
and some insecticide
work by inhibiting them. An MAOI effect is especially important for chlordimeform
(although one result shows little or no effect in ''Periplaneta americana
or may not
be an MAOI in ''Locusta migratoria
MAO activity has been detected in ''Rhipicephalus microplus
'' and chlordimeform is an MAOI in ''R. m.''.
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 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.
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.
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.
A possible link between predisposition to novelty seeking
and a genotype
of the MAO-A gene has been found.
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
Unlike many other enzymes, MAO-B activity is increased during aging in the brain of humans and other mammals. Increased MAO-B activity was also found in the pineal gland
of aging rats.
This may contribute to lowered levels of monoamines in aged brain and pineal gland.
*Monoamine oxidase inhibitor
Category:Single-pass transmembrane proteins