Monoamine oxidase is a mitochondrial membrane flavin-containing enzyme that catalyzes the oxidative deamination of monoamines
according to the following equation: Substrates for this enzyme include several monoamines, secondary and tertiary amines in which the amine substrates are methyl groups.
The amine must be attached to an unsubstituted methylene group, and compounds having substitution at the α-carbon atom are poor
substrates for MAO (e.g., aniline, amphetamine, and ephedrine) but are oxidized by the microsomal CYP450 enzymes rather than by MAO. For secondary and tertiary amines, alkyl groups larger than a methyl and branched alkyl groups (i.e., isopropyl, t-butyl, or
β-phenylisopropyl) inhibit MAO oxidation, but such substrates may function as reversible inhibitors of MAO. Nonselective irreversible
inhibitors of MAO include hydrazides (phenelzine) and tranylcypromine and the MAO-B selective inhibitors pargyline and selegiline.
Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural tissues, and hepatic
MAO has a crucial defensive role in inactivating circulating monoamines or those that originated in the gastrointestinal tract and were
absorbed into the systemic circulation (e.g., tyramine). Two types of MAO are isolated: MAO-A, and MAO-B. They show dissimilar substrate preferences and different sensitivities to inhibitors.
The type MAO-A is found mainly in peripheral adrenergic nerve terminals and shows substrate preference for 5-hydroxytryptamine,
norepinephrine, and epinephrine. The type MAO-B is found principally in platelets and shows selectivity for nonphenolic, lipophilic
β-phenethylamines. Common substrates to both MAO-A and MAO-B are dopamine, tyramine, and other monophenolic phenylethylamines.
