Catechol-O-methyl transferase

Catechol-O-methyl transferase

Catechol-O-methyl transferase (COMT) is an enzyme that plays a crucial role in the metabolism of catecholamines, which include neurotransmitters such as dopamine, epinephrine, and norepinephrine. This enzyme is responsible for the transfer of a methyl group from S-adenosylmethionine (SAM) to catecholamines, thereby inactivating them. COMT is a key player in the regulation of mood, cognition, and stress response.

Structure and Function

COMT is encoded by the COMT gene located on chromosome 22q11.21. The enzyme exists in two forms: a soluble form (S-COMT) and a membrane-bound form (MB-COMT). The soluble form is found in the cytoplasm, while the membrane-bound form is associated with cellular membranes.

The primary function of COMT is to catalyze the O-methylation of catecholamines. This reaction involves the transfer of a methyl group from SAM to the hydroxyl group of catecholamines, resulting in the formation of methoxy-catecholamines. This process is essential for the degradation of catecholamines and the regulation of their levels in the synaptic cleft.

Genetic Variability

The COMT gene is known for its genetic polymorphisms, the most studied of which is the Val158Met polymorphism. This single nucleotide polymorphism (SNP) results in a valine (Val) to methionine (Met) substitution at position 158 of the enzyme. The Met variant is associated with lower enzymatic activity compared to the Val variant, leading to higher levels of dopamine in the prefrontal cortex.

Clinical Significance

COMT has been implicated in various psychiatric and neurological disorders. The Val158Met polymorphism, in particular, has been studied in relation to schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder (ADHD). Individuals with the Met/Met genotype may have an increased risk of developing these conditions due to altered dopamine metabolism.

COMT inhibitors, such as entacapone and tolcapone, are used in the treatment of Parkinson's disease. These drugs inhibit the activity of COMT, thereby increasing the availability of dopamine in the brain and improving motor symptoms in patients.

Research and Future Directions

Ongoing research is focused on understanding the role of COMT in cognitive function and its potential as a therapeutic target for neuropsychiatric disorders. Studies are also exploring the impact of COMT polymorphisms on individual responses to pharmacological treatments.

Also see

• Dopamine
• Neurotransmitter
• Parkinson's disease
• Schizophrenia
• Genetic polymorphism