monoaminoxidase

Monoamine oxidase (MAO) is a flavin adenine dinucleotide (FAD)-dependent enzyme that oxidatively deaminates monoamines, a group of neurotransmitters and related amines. The reaction converts substrates such as dopamine, norepinephrine, serotonin, and phenylethylamine into their corresponding aldehydes, releasing ammonia and hydrogen peroxide in the process. The aldehydes are subsequently metabolized to acids or other compounds.

There are two isoforms, MAO-A and MAO-B, encoded by the MAOA and MAOB genes, respectively. Both are located on the outer mitochondrial membrane and are widely distributed in tissues. MAO-A is relatively abundant in the gut, placenta, and certain brain regions and preferentially metabolizes serotonin and norepinephrine. MAO-B is abundant in the brain and platelets and metabolizes phenylethylamine, with both isoforms contributing to dopamine catabolism.

Physiologically, MAO activity regulates the levels of monoamines, influencing mood, sleep, appetite, and vascular tone. The production of hydrogen peroxide links MAO activity to cellular redox state, and byproducts are further processed by cellular antioxidant systems.

Pharmacologically, MAO inhibitors (MAOIs) are used as antidepressants and in the treatment of Parkinson’s disease. Irreversible MAOIs include phenelzine, tranylcypromine, and isocarboxazid; reversible inhibitors include moclobemide. Selegiline is a selective MAO-B inhibitor at certain doses. Because MAOIs can elevate monoamines, dietary restrictions are advised to avoid tyramine-induced hypertensive crises (the cheese effect). Interactions with other serotonergic drugs can cause serotonin syndrome.

MAO thus plays a central role in monoaminergic signaling and is a notable target in psychiatric and neurological therapy.