Membrane-bound catechol-O-methyltransferase (MB-COMT) (MB-COMT)

Membrane-bound catechol-O-methyltransferase (MB-COMT) is a bitopic enzyme anchored to the rough endoplasmic reticulum, primarily expressed in the central nervous system and peripheral tissues like the liver and kidneys [1.3.2, 1.4.1]. It plays a critical role in the inactivation of catecholamine neurotransmitters, such as dopamine, epinephrine, and norepinephrine, by transferring a methyl group from S-adenosyl-L-methionine to the catechol ring [1.2.1, 1.4.2]. In the brain, MB-COMT is the dominant isoform responsible for dopamine clearance in the prefrontal cortex, where dopamine transporters are less abundant [1.2.2, 1.3.5]. This enzyme is a key therapeutic target in Parkinson's disease, as its inhibition prevents the peripheral metabolism of levodopa into 3-O-methyldopa, thereby increasing levodopa's bioavailability and brain penetration [1.1.3, 1.3.2]. Genetic polymorphisms, most notably the Val158Met (rs4680) variant, significantly alter MB-COMT activity and have been associated with cognitive performance, pain sensitivity, and psychiatric conditions like schizophrenia [1.2.3, 1.3.5]. Pharmacological inhibitors such as entacapone and opicapone are used clinically to manage motor fluctuations in Parkinson's patients [1.1.2, 1.1.4]. However, the use of certain inhibitors like tolcapone is limited by risks of severe hepatotoxicity, requiring stringent liver function monitoring [1.1.1, 1.1.3].

Other names

MB-COMTMembrane-bound COMTCatechol-O-methyltransferase membrane-bound isoformCatechol methyltransferaseCatecholamine O-methyltransferase

Inhibition of the COMT enzyme to prevent the O-methylation of levodopa and dopamine, thereby increasing the half-life and bioavailability of levodopa in the treatment of Parkinson's disease.