COMT

Catechol O-methyltransferase (COMT) is the enzyme responsible for the O-methylation of endogenous neurotransmitters and of xenobiotic substances and hormones incorporating catecholic structures. COMT is present in mammals as soluble (S-COMT) and membrane-bound (MB-COMT) forms. S-COMT is the predominant form of COMT in the peripheral organs and MB-COMT is more abundant in the Central Nervous System.

Physiological substrates of COMT include L-dopa, catecholamines (dopamine, norepinephrine, and epinephrine), their hydroxylated metabolites, catecholestrogens, ascorbic acid, and dihydroxyindolic intermediates of melanin. Specifically, COMT plays a critical role in the inactivation and metabolism of dopamine and other catechol compounds. The enzyme reduces a catechol molecule in order to prevent genomic damage through DNA adduct formation or via oxygen radicals produced from the redox cycling of catechols. COMT is a druggable biological target for the treatment of various central and peripheral nervous system disorders, including Parkinson's disease, depression, schizophrenia, and other dopamine deficiency-related diseases.