Editing Monoamine oxidase (section)

== Function ==
[[File:Noradrenaline breakdown.svg|thumb|350px|Norepinephrine degradation. Monoamine oxidase is shown left in the blue box.<ref name=Rang&Dale6th-11-4>Figure 11-4 in: {{cite book | vauthors = Flower R, Rang HP, Dale MM, Ritter JM | title = Rang & Dale's pharmacology | publisher = Churchill Livingstone | location = Edinburgh | year = 2007 | isbn = 978-0-443-06911-6 }}</ref>]]

Monoamine oxidases catalyze the [[oxidative deamination]] of monoamines. In the first part of the reaction, [[Cofactor (biochemistry)|cofactor]] [[Flavin adenine dinucleotide|FAD]] oxidizes the substrate yielding the corresponding [[imine]] which converts the cofactor into its reduced form [[FADH2]]. The imine is then non-enzymatically hydrolyzed to the corresponding [[ketone]] (or [[aldehyde]]) and [[ammonia]]. [[Oxygen]] is used to restore the reduced [[Flavin adenine dinucleotide|FADH2]] cofactor back to the active [[FAD]] form. Monoamine [[oxidase]]s contain the covalently bound [[cofactor (biochemistry)|cofactor]] [[Flavin adenine dinucleotide|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 within [[Monoamine oxidase B|MAO-B]],  407 and 444 within [[MAO-A]]) 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<ref>{{cite journal| vauthors = Vianello R, Repič M, Mavri J |date=2012-10-25|title=How are Biogenic Amines Metabolized by Monoamine Oxidases? |journal=European Journal of Organic Chemistry |volume=2012 |issue=36 |pages=7057–7065 |doi=10.1002/ejoc.201201122}}</ref>) although there is insufficient evidence to support any of them.<ref name="pmid22022344">{{cite journal | vauthors = Gaweska H, Fitzpatrick PF | title = Structures and Mechanism of the Monoamine Oxidase Family | journal = Biomolecular Concepts | volume = 2 | issue = 5 | pages = 365–377 | date = October 2011 | pmid = 22022344 | pmc = 3197729 | doi = 10.1515/BMC.2011.030 }}</ref>

In 2021, it was discovered that MAO-B does not mediate dopamine [[catabolism]] in the rodent [[striatum]] but instead participates in striatal [[γ-aminobutyric acid]] (GABA) synthesis from [[putrescine]] and that synthesized GABA in turn inhibits [[dopaminergic]] [[neuron]]s in this brain area.<ref name="NamSaJu2022">{{cite journal | vauthors = Nam MH, Sa M, Ju YH, Park MG, Lee CJ | title = Revisiting the Role of Astrocytic MAOB in Parkinson's Disease | journal = Int J Mol Sci | volume = 23 | issue = 8 | date = April 2022 | page = 4453 | pmid = 35457272 | pmc = 9028367 | doi = 10.3390/ijms23084453 | doi-access = free | url = }}</ref><ref name="ChoKimSim2021" /> It has been found that MAO-B, via the putrescine pathway, importantly mediates GABA synthesis in [[astrocyte]]s in various brain areas, including in the [[hippocampus]], [[cerebellum]], striatum, [[cerebral cortex]], and [[substantia nigra pars compacta]] (SNpc).<ref name="NamSaJu2022" /><ref name="ChoKimSim2021" /> These findings may warrant a rethinking of the actions of [[MAO-B inhibitor]]s in the treatment of [[Parkinson's disease]].<ref name="NamSaJu2022" /><ref name="ChoKimSim2021" />