Catechol O-methyltransferase (soluble isoform) (S-COMT)

Catechol O-methyltransferase (COMT) is a crucial enzyme involved in the degradation of catecholamines, including dopamine, epinephrine, and norepinephrine, as well as catechol estrogens (UniProt P21964). It exists in two primary forms: a soluble isoform (S-COMT) and a membrane-bound isoform (MB-COMT), with S-COMT being the predominant form in peripheral tissues such as the liver and kidneys. In the context of Parkinson's disease, S-COMT is a major therapeutic target because it metabolizes levodopa into 3-O-methyldopa, reducing the amount of levodopa available to cross the blood-brain barrier (PubMed, PMID: 11036155). By inhibiting S-COMT, drugs like entacapone and opicapone increase the half-life of levodopa and enhance its delivery to the brain, thereby alleviating motor fluctuations and "off" time in patients (StatPearls, 2023). Beyond Parkinson's, variations in the COMT gene, such as the Val158Met polymorphism, have been extensively studied for their impact on cognitive function, pain sensitivity, and psychiatric disorders due to their effect on prefrontal cortex dopamine levels (NIH, 2022).

Other names

S-COMTSoluble catechol-O-methyltransferaseCOMT

Inhibition of the COMT enzyme to prevent the O-methylation of levodopa and dopamine, thereby increasing the bioavailability of levodopa and prolonging the duration of action of dopamine in the central nervous system (StatPearls, 2023).