Catechol-O-methyl transferase (COMT) (EC 18.104.22.168) is an enzyme first discovered by biochemistJulius Axelrod. COMT is the name given to the gene that codes for this enzyme. The O in the name stands for oxygen, not for ortho.
Catechol-O-methyl transferase is involved in the inactivation of the catecholamineneurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). COMT is an intracellular enzyme located in the postsynaptic neuron. Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids, are substrates of COMT.
L-DOPA, a precursor of catecholamines, is an important substrate of COMT. COMT inhibitors, like entacapone, save L-dopa from COMT and prolong the action of L-DOPA. Entacapone is a widely-used adjunct drug of L-DOPA therapy. When given with an inhibitor of dopa decarboxylase (carbidopa or benserazide), L-DOPA is optimally saved. This "triple therapy" is becoming a standard in the treatment of Parkinson's disease.
A functional single nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyl transferase has been shown to affect cognitive tasks broadly related to executive function, such as set shifting, response inhibition, abstract thought, and the acquisition of rules or task structure. This polymorphism in the COMT gene results in the substitution of the amino acid valine for methionine. It has been shown that this valine variant catabolizes dopamine at up to four times the rate of its methionine counterpart, resulting in a significant reduction of synaptic dopamine following neurotransmitter release, ultimately reducing dopaminergic stimulation of the post-synaptic neuron. As a consequence, neurons with valine-variant COMT show higher levels of activation during certain cognitive tasks, as they require higher levels of neuron firing to achieve the same level of post-synaptic stimulation.
The link between impairments in these sorts of cognitive tasks and the COMT gene is thought to be mediated by an effect on dopamine signaling in the frontal lobes.
Comparable effects on similar cognitive tasks, the frontal lobes, and the neurotransmitter dopamine have also all been linked to schizophrenia. It is not surprising, then, that an inherited variant of COMT is thought to be one of the genetic factors that may predispose someone to developing schizophrenia later in life, naturally or due to adolescent-onset cannabis use.
COMT inhibitors are found in green tea. Drinking green tea is, therefore, thought to provide a useful short-term boost to antidepressant medication by increasing the half-life of extracellular norepinephrine and dopamine. Tea may also help reduce the risk of breast cancer.
COMT inhibitors include tolcapone and entacapone.
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