doi: 10.1021/bi00537a006.
Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase
- PMID: 7082642
- DOI: 10.1021/bi00537a006
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Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase
Biochemistry.
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Abstract
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.
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