Monoamine oxidase (mitochondrial) (MAO)

Monoamine oxidase is a family of flavin-containing enzymes located in the outer mitochondrial membrane, responsible for the oxidative deamination of monoamines such as neurotransmitters (e.g., serotonin, dopamine, norepinephrine) and dietary amines[1][4]. There are two closely related isoforms, MAO-A and MAO-B, that differ in substrate specificity and inhibitor sensitivity. MAO-A primarily degrades serotonin and norepinephrine, while MAO-B acts preferentially on phenethylamine and benzylamine, with both contributing to dopamine metabolism depending on tissue context[1][4]. These enzymes play central roles in neurochemistry, neurodegeneration, and are targets for MAO inhibitor drugs in the treatment of depression, Parkinson’s disease, and anxiety disorders[1][3][4]. MAO-B is also implicated in GABA synthesis in astrocytes, further regulating neuronal inhibition[1]. Their structure includes a membrane-anchoring domain, a FAD-binding domain, and active site cavities critical for substrate and inhibitor selectivity[2][3][4]. Inhibition or genetic variation of MAOs can produce profound therapeutic and adverse effects due to their central role in neurotransmitter metabolism.

Other names

Monoamine oxidase A (MAO-A)Monoamine oxidase B (MAO-B)mitochondrial MAOtyramine oxidase (historical)

Irreversible inhibition: Covalent modification of the FAD cofactor or active site residues (as with tranylcypromine); Reversible inhibition: Competitive binding to substrate or entrance cavity; Enzyme activity reduction: Blocks oxidative deamination, increases monoamine levels.