COMT

About COMT

COMT Catechol O Methyltransferase on chromosome 22q11.21 encodes an enzyme that inactivates catecholamines, including dopamine, norepinephrine, and epinephrine, as well as catechol estrogens and catechol drugs, by transferring a methyl group from S adenosylmethionine. The common Val158Met polymorphism produces enzyme variants with different stability, the Val form having higher activity and the Met form lower activity, which affects dopamine levels especially in the prefrontal cortex, where dopamine transporters are scarce. This polymorphism has been extensively studied in relation to working memory, executive function, pain sensitivity, and stress responses, although many reported associations with psychiatric conditions have been inconsistent across studies. COMT lies within the region deleted in 22q11.2 deletion syndrome, also called DiGeorge or velocardiofacial syndrome, which carries a markedly increased risk of psychosis, and reduced COMT dosage has been studied as one contributor. COMT inhibitors such as entacapone, opicapone, and tolcapone are used in Parkinson disease to reduce peripheral breakdown of levodopa and prolong its effect. The enzyme was described by Julius Axelrod in 1957, part of the work on neurotransmitter metabolism recognized by his 1970 Nobel Prize.