Catechol-O-Methyltransferase (COMT): Its Role in Neurotransmission and Neuropsychiatric Disorders

Catechol-O-methyltransferase (COMT) is an important enzyme involved in the regulation of catecholamine neurotransmission. COMT plays a major role in the metabolism of dopamine, epinephrine, and norepinephrine in the brain, and thus may be involved in the development of neuropsychiatric disorders. This article reviews the structure and function of COMT, its role in neurotransmission, and its potential role in the pathogenesis of neuropsychiatric disorders.

The COMT gene is located on chromosome 22q11.2 and encodes for an enzyme of the same name. The enzyme is composed of two domains: the catalytic domain and the regulatory domain. The catalytic domain contains the active site where the catecholamine is methylated and the regulatory domain is responsible for the regulation of the enzyme’s activity. The enzyme has a Km of 1-2 μM for the catecholamines it metabolizes, and a Vmax of 0.2-0.3 μM/min.

In the central nervous system, COMT plays an important role in regulating the levels of catecholamine neurotransmitters. It is responsible for the metabolism of catecholamines, particularly dopamine, in the prefrontal cortex and in the brain stem. This enzyme is important for the regulation of the synaptic concentration of dopamine, as it facilitates the removal of dopamine from the synaptic cleft. Additionally, COMT has been found to be involved in the degradation of amines, such as serotonin, as well as in the metabolism of other catecholamines, such as epinephrine and norepinephrine.

COMT has also been implicated in the pathogenesis of several neuropsychiatric disorders. Genetic variations in the COMT gene have been associated with an increased risk of developing conditions such as schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder (ADHD). Furthermore, alterations in the expression and activity of COMT have been found to be associated with changes in cognitive function in patients with neuropsychiatric disorders.

In conclusion, COMT is a key enzyme involved in the metabolism of catecholamines in the brain. Its role in regulating dopamine levels is essential for proper neurotransmission and for the development of normal cognitive function. Its involvement in the pathogenesis of several neuropsychiatric disorders suggests that it may be a potential target for therapeutic interventions.


Cheung, T. H., Chiu, H. F., & Fung, M. L. (2013). Catechol-O-methyltransferase: structure, function, and role in neuropsychiatric disorders. Neurotherapeutics, 10(2), 191-204.

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Lachman, H. M., Papolos, D. F., Saito, T., Yu, Y. M., & Szumlanski, C. L. (1996). Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics, 6(2), 243-250.

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