Catechol-O-methyltransferase

Catechol-O-methyltransferase (COMT) is an enzyme that is involved in the metabolism of catecholamines. It is encoded by the COMT gene in humans. This enzyme plays a crucial role in the degradation of catecholamines, such as dopamine, epinephrine, and norepinephrine.

Function

COMT is responsible for the methylation of catecholamines, which is a process that involves the transfer of a methyl group from S-adenosyl methionine (SAM) to the catecholamine. This reaction results in the formation of methoxy-derivatives, which are less active and more easily excreted from the body. The enzyme exists in two forms: a soluble form (S-COMT) and a membrane-bound form (MB-COMT).

Genetic Variability

The COMT gene exhibits genetic polymorphism, which can affect the enzyme's activity. One of the most studied polymorphisms is the Val158Met variant, where a substitution of valine (Val) with methionine (Met) at position 158 results in a significant reduction in enzyme activity. This polymorphism has been associated with various neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder (ADHD).

Clinical Significance

Alterations in COMT activity can have significant implications for mental health. For instance, individuals with the Met/Met genotype of the Val158Met polymorphism tend to have higher levels of dopamine in the prefrontal cortex, which can affect cognitive functions and susceptibility to stress. COMT inhibitors, such as entacapone and tolcapone, are used in the treatment of Parkinson's disease to prolong the effect of levodopa by preventing its breakdown.

Related Enzymes

COMT is part of a larger family of methyltransferases, which includes other enzymes such as histamine N-methyltransferase and phenylethanolamine N-methyltransferase. These enzymes also play roles in the metabolism of various biogenic amines.

See Also

• Dopamine
• Epinephrine
• Norepinephrine
• Parkinson's disease
• Schizophrenia
• Bipolar disorder
• Attention deficit hyperactivity disorder
• Methylation
• S-adenosyl methionine