Function
Catechol-O-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids, are substrates of COMT.
Levodopa, a precursor of catecholamines, is an important substrate of COMT. COMT inhibitors, like entacapone, save levodopa from COMT and prolong the action of levodopa. Entacapone is a widely used adjunct drug of levodopa therapy. When given with an inhibitor of dopa decarboxylase (carbidopa or benserazide), levodopa is optimally saved. This "triple therapy" is becoming a standard in the treatment of Parkinson's disease.
Specific reactions catalyzed by COMT include:
- Dopamine → 3-Methoxytyramine
- DOPAC → HVA (homovanillic acid)
- Norepinephrine → Normetanephrine
- Epinephrine → Metanephrine
- Dihydroxyphenylethylene glycol (DOPEG) → Methoxyhydroxyphenylglycol (MOPEG)
- 3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid (VMA)
In the brain, COMT-dependent dopamine degradation is of particular importance in brain regions with low expression of the presynaptic dopamine transporter (DAT), such as the prefrontal cortex. This process is supposed to take place in postsynaptic neurons, as, in general, COMT is located intracellularly in the CNS.
COMT can also be found extracellularly, although extracellular COMT plays a less significant role in the CNS than it does peripherally. Despite its importance in neurons, COMT is actually primarily expressed in the liver.
Read more about this topic: Catechol-O-methyl Transferase
Famous quotes containing the word function:
“The function of comedy is to dispel ... unconsciousness by turning the searchlight of the keenest moral and intellectual analysis right on to it.”
—George Bernard Shaw (1856–1950)
“The press and politicians. A delicate relationship. Too close, and danger ensues. Too far apart and democracy itself cannot function without the essential exchange of information. Creative leaks, a discreet lunch, interchange in the Lobby, the art of the unattributable telephone call, late at night.”
—Howard Brenton (b. 1942)
“Morality and its victim, the mother—what a terrible picture! Is there indeed anything more terrible, more criminal, than our glorified sacred function of motherhood?”
—Emma Goldman (1869–1940)