catechol O-methyltransferase (COMT)

Function

• catalyzes the O-methylation, & thus inactivation, of catecholamine neurotransmitters & catechol hormones
• transfers methyl group from SAM to catecholamines
• both a soluble & membrane-bound form from same precursor
• shortens the biological half-lives of certain neuroactive drugs, including L-DOPA, alpha-methyl DOPA & isoproterenol

S-adenosyl-L-methionine + a catechol
              <-->
S-adenosyl-L-homocysteine + a guaiacol

Cofactor: binds 1 Mg+2 per subunit (putative)

Structure

• N-terminus is blocked
• belongs to the mammalian catechol-O-methyltransferase family

Compartment

• isoform soluble: cytoplasm
• isoform membrane-bound: cell membrane, extracellular side

Alternative initiation

• named isoforms=2

Expression

• brain, liver, placenta, lymphocytes & erythrocytes

Polymorphism

• low enzyme activity alleles are associated with genetic susceptibility to alcoholism
• val158met polymorphism predicts placebo effect in irritable bowel syndrome

Laboratory

• COMT gene mutation

More general terms

• O-methyl transferase

Additional terms

• catechol O-methyltransferase 2 (COMT2)
• catecholamine metabolism

Database

• UniProt: http://www.uniprot.org/uniprot/P21964.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1312
• OMIM: https://mirror.omim.org/entry/103780
• OMIM: https://mirror.omim.org/entry/116790