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Pathway Description
Monoamine Oxidase-A Deficiency (MAO-A)
Homo sapiens
Disease Pathway
Created: 2013-08-29
Last Updated: 2025-01-24
Momoamine oxidase A (MAO-A) deficiency, or Brunner syndrome, is an X-linked recessive genetic disorder caused by a mutation in the MAOA gene that encodes for monoamine oxidase A. As such it is almost exclusively found in men.
MAO-A is an enzyme that catalyzes the deamination of amines such as epinephrine, dopamine and tyramine, as part of the tyrosine metabolism pathway.
In this disorder, some neurotransmitters such as serotonin and dopamine build up in the brain due to their inability to be properly metabolized. Since serotonin helps to regulate emotions and mood, with epinephrine and norepinephrine regulating stress, the unnecessary presence of the chemicals in the brain can lead to poor impulse control, aggression and other effects. The buildup of chemicals may also damage the brain, leading to a lower IQ in individuals with this disorder. In addition, foods containing the compounds that cannot be broken down, such as tyramine, can cause episodes of increased symptoms in the patients.
In the subpathway that converts dopamine to homovanillic acid, there are two instances of MAO-A that are inactivated in this disorder, both in different branches. The first reaction converts dopamine to 3,4-dihydroxyphenylacetaldehyde, while the second converts 3-methoxytyramine to homovanillin. With the inactivation of MAO-A, 3-methoxytyramine builds up as there are no reactions that use it, and both of these paths lead to a decrease in the concentration of homovanillic acid, as there are no other reactions present that produce it. Another reaction, this time converting tyramine to homovanillin, is also prevented by the lack of MAO-A, which leads to an accumulation of tyramine in the body.
In another branch of tyrosine metabolism, the absence of MAO-A prevents the oxidation of norepinephrine and epinephrine into 3,4-dihydroxymandelaldehyde. Its absence also prevents the oxidative deamination of metanephrine and normetanephrine into 3-methoxy-4-hydroxyphenylglycolaldehyde. As this is no longer produced, it leads to a decrease in the concentration of vanillylmandelic acid, which is produced from 3-methoxy-4-hydroxyphenylglycolaldehyde in a reaction catalyzed by aldehyde dehydrogenase.
References
Monoamine Oxidase-A Deficiency (MAO-A) References
[Metagen: MONOAMINE OXIDASE-A DEFICIENCY (MAO-A)](http://metagene.de/program/d.prg?id_d=446)
[OMIM: 309850](http://omim.org/entry/309850})
[NIH](https://rarediseases.info.nih.gov/diseases/3531/monoamine-oxidase-a-deficiency)
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Pubmed: 25807999
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