Catechol O-methyltransferase (COMT) (COMT)

Catechol O-methyltransferase (COMT) is a magnesium-dependent enzyme that plays a vital role in the metabolic degradation of catecholamines, such as dopamine, norepinephrine, and epinephrine, as well as catechol estrogens [1, 4]. It functions by transferring a methyl group from S-adenosyl-L-methionine (SAM) to a hydroxyl group on the catechol ring, effectively terminating the biological activity of these signaling molecules [1, 9]. The enzyme exists in two distinct isoforms: a soluble form (S-COMT) found in various peripheral tissues and a membrane-bound form (MB-COMT) that is particularly abundant in the brain's prefrontal cortex [1, 10]. In the management of Parkinson's disease, COMT is a primary therapeutic target; COMT inhibitors like entacapone and opicapone are administered alongside levodopa to inhibit its peripheral metabolism, thus enhancing its delivery to the central nervous system [6, 11]. Furthermore, genetic variations in the COMT gene, specifically the Val158Met polymorphism, have been linked to individual differences in executive function, pain sensitivity, and the risk of psychiatric disorders including schizophrenia [2, 12]. While these inhibitors are generally effective, safety concerns such as severe liver toxicity have been noted with certain agents like tolcapone, necessitating careful clinical monitoring [8, 11].

Other names

Catechol methyltransferaseHEL-S-98nS-COMTMB-COMTCatecholamine O-methyltransferase

Inhibition of the catechol O-methyltransferase enzyme to prevent the O-methylation and subsequent inactivation of catecholamines and levodopa, thereby increasing their bioavailability and duration of action.