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. a catechol + S-adenosyl-L-methionine = a guaiacol + H(+) + S-adenosyl-L-homocysteine 2-hydroxyestrone + S-adenosyl-L-methionine = 2-hydroxy-3-methoxy-estrone + H(+) + S-adenosyl-L-homocysteine 4-hydroxyestrone + S-adenosyl-L-methionine = 4-methoxyestrone + H(+) + S-adenosyl-L-homocysteine 2-hydroxyestrone + S-adenosyl-L-methionine = 2-methoxyestrone + H(+) + S-adenosyl-L-homocysteine 4-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 4-methoxy-17beta-estradiol + H(+) + S-adenosyl-L-homocysteine 2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2-hydroxy-3-methoxy-17beta-estradiol + H(+) + S-adenosyl-L-homocysteine 2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2-methoxy-17beta-estradiol + H(+) + S-adenosyl-L-homocysteine Binds 1 Mg(2+) ion per subunit. kcats are 6.8 min(-1), 3.4 min(-1), 3.3 min(-1) and 6.7 min(-1) with 2-hydroxy-17beta-estradiol, 4-hydroxy-17beta-estradiol, 2-hydroxyestrone and 4-hydroxyestrone as subrates, respectively. Brain, liver, placenta, lymphocytes and erythrocytes. The N-terminus is blocked. 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]. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Catechol-O-methyl transferase entry