Monoamine oxidase
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.
[7] 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.
Autopsied brains demonstrated the predicted increased concentration of MAO-A in regions dense in serotonergic neurotransmission, however MAO-B only correlated with norepinephrine.
[14][15] It has been found that MAO-B, via the putrescine pathway, importantly mediates GABA synthesis in astrocytes in various brain areas, including in the hippocampus, cerebellum, striatum, cerebral cortex, and substantia nigra pars compacta (SNpc).
[medical citation needed] Specific reactions catalyzed by MAO include:[18][19] Other endogenous substrates of MAO include telemethylhistamine, a metabolite of histamine, and N-acetylputrescine, a metabolite of putrescine and a precursor and metabolic intermediate in a minor metabolic pathway resulting in the synthesis of γ-aminobutyric acid (GABA).
[28][32][33][34] Examples include substituted phenethylamine sympathomimetics and sympatholytics like phenylephrine, propranolol, and pronethalol, substituted tryptamine serotonergic agents like dimethyltryptamine (DMT), 5-MeO-DMT, bufotenin, almotriptan, rizatriptan, and sumatriptan, and other compounds like bicifadine, citalopram, CP-409092, KW-2449, milacemide, MPTP, nomifensine, primaquine, rivaroxaban, sertraline, and ticlopidine, among others.
Unusually high or low levels of MAOs in the body have been associated with schizophrenia,[35][36] depression,[37] attention deficit disorder,[38] substance abuse,[39] migraines,[40][41] and irregular sexual maturation.
[42] 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.
[medical citation needed] MAO activity has been detected in Rhipicephalus microplus and chlordimeform is an MAOI in R. m..[55] 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.
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.
