Monoamine oxidase A and Monoamine oxidase B (MAO-A and MAO-B)

Monoamine oxidases A and B (**MAO-A**, **MAO-B**) are mitochondrial outer membrane-bound enzymes that catalyze the oxidative deamination of endogenous biogenic amines—including key neurotransmitters like serotonin, dopamine, norepinephrine—and exogenous amines found in food. They play a central role both in regulating mood-related neurochemistry within the central nervous system and detoxifying dietary amines peripherally. Structurally related but functionally distinct isoforms encoded by separate genes (*MAOA*, *MAOB*) share about ~70% sequence identity but differ significantly at their active sites—resulting in different substrate preferences. Both isoforms contain a covalently bound flavin adenine dinucleotide cofactor essential for their catalytic activity. While **MAO-A preferentially metabolizes serotonin and norepinephrine**, **MAO-B is more involved with phenylethylamine metabolism**, though both can catabolize dopamine under different physiological contexts. Recent research has shown that beyond classic roles in catecholaminergic metabolism, **MAO-B also mediates GABA synthesis from putrescine within astrocytes**, influencing neuronal inhibition pathways relevant to diseases like Parkinson’s. Clinically important as therapeutic targets since their inhibition increases synaptic availability of mood-regulating neurotransmitters—forming the basis for several classes of antidepressant drugs (**monoamine oxidase inhibitors/MAOI**) as well as adjunct therapies for neurodegenerative diseases such as Parkinson's disease. However, use is limited by significant safety concerns including dangerous interactions with certain foods/drugs due to impaired breakdown capacity leading to toxic accumulation.

Other names

MAOA (gene for monoamine oxidase A)MAOB (gene for monoamine oxidase B)Monoamine oxidasesFlavin-containing amine oxidoreductases

Drugs targeting these enzymes typically act by: - Inhibiting the oxidative deamination activity of MAOs, thereby increasing synaptic concentrations of monoaminergic neurotransmitters such as serotonin, dopamine, and norepinephrine. * Some inhibitors are reversible; others are irreversible. * Selectivity can be for either MAO-A or MAO-B. These are known as monoamine oxidase inhibitors (MAOIs).