Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase.
Km values for dopamine and S-adenosylmethionine (AdoMet) of human brain membrane-bound catechol O-methyltransferase are 3.3 microM and 3.1 microM, respectively. S-Adenosylhomocysteine is a very potent competitive inhibitor with respect to AdoMet with a Ki value of 1 microM. Product inhibition patterns strongly support a steady-state compulsory-order ternary complex mechanism in which AdoMet binds to the enzyme before dopamine. Inhibition of membrane-bound COMT by tropolone is competitive with respect to dopamine (Ki = 5 microM) and uncompetitive with respect to AdoMet and is consistent with this type of mechanism. The mechanism proposed is different from that suggested for soluble catechol O-methyltransferases.
D001921:Brain / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008745:Methylation; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000378:metabolism; D014334:Tropolone / Q000494:pharmacology
D014334:Tropolone; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D002394:Catechol O-Methyltransferase; C001746:3-methoxytyramine; D004298:Dopamine