EC2.1.1.6
カテコールアミンを基質として、３位または４位のヒドロキシ基をメトキシ化する。S-アデノシルメチオニンをメチルドナーとする。
３位メトキシ体と４位メトキシ体は５：１の比率で生成する。
カテコールアミンは活性を失う。
Function
O-メチル化により神経伝達物質のカテコラミンの不活性化をおこなう。L-DOPAなどの半減期の短縮に関与する。
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Catalytic activity
SAMからメチル基の転移
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol.
Cofactor
Binds 1 magnesium ion per subunit.
Subcellular location
Isoform Soluble: Cytoplasm.
Isoform Membrane-bound: Cell membrane; Single-pass type II membrane protein; Extracellular side.
Tissue specificity
Brain, liver, placenta, lymphocytes and erythrocytes.
Post-translational modification
The N-terminus is blocked.
Polymorphism
Two alleles, COMT*1 or COMT*H with Val-158 and COMT*2 or COMT*L with Met-158 are responsible for a three to four-fold difference in enzymatic activity.
Low enzyme activity alleles are associated with genetic susceptibility to alcoholism [MIM:103780].
Sequence similarities
Belongs to the mammalian catechol-O-methyltransferase family.
Mass spectrometry
Molecular mass is 24352±2 Da from positions 52 - 271. Determined by ESI. Ref.11
