Monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) (MAO-A and COMT)

Monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) are the two primary enzymes responsible for the metabolic degradation of catecholamines and other monoamine neurotransmitters derived from tyrosine (UniProt: P21397, P22735). MAO-A is located on the outer mitochondrial membrane and performs oxidative deamination of serotonin, norepinephrine, and dopamine, while COMT catalyzes the O-methylation of catechol substrates using S-adenosyl-L-methionine as a methyl donor (PubMed: 25637919). Together, these enzymes maintain the homeostatic balance of neurotransmitters in the central nervous system and peripheral tissues. Dysregulation of this metabolic pathway is heavily implicated in neuropsychiatric and neurodegenerative conditions, such as major depressive disorder and Parkinson's disease (StatPearls: Monoamine Oxidase Inhibitors). Pharmacological inhibition of MAO-A is used to treat depression by increasing the synaptic availability of monoamines. COMT inhibitors are utilized as adjunct therapy in Parkinson's disease to prevent the peripheral breakdown of levodopa, thereby extending its therapeutic half-life and efficacy (StatPearls: COMT Inhibitors).

Other names

MAOACOMTAmine oxidase [flavin-containing] ACatechol-O-methyltransferaseMonoamine oxidase type A

Inhibition of these enzymes prevents the metabolic breakdown of monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin, thereby increasing their synaptic availability and prolonging their physiological effects.