Kinetic Studies on the O-Methylation of Dopamine by Human Brain Membrane-Bound Catechol O-Methyltransferase

A. Jennifer Rivett; Jerome A. Roth

doi:10.1021/bi00537a006

Kinetic Studies on the O-Methylation of Dopamine by Human Brain Membrane-Bound Catechol O-Methyltransferase

A. Jennifer Rivett
, Jerome A. Roth

Pharmacology and Toxicology

SUNY Buffalo

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

K_m values for dopamine and S-adenosylmethionine (AdoMet) of human brain membrane-bound catechol O-methyltransferase are 3.3 µM and 3.1 µM, respectively. S-Adenosylhomocysteine is a very potent competitive inhibitor with respect to AdoMet with a K_i value of 1 µM. 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 (K_i = 5 µM) 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.

Original language	English
Pages (from-to)	1740-1742
Number of pages	3
Journal	Biochemistry
Volume	21
Issue number	8
DOIs	https://doi.org/10.1021/bi00537a006
State	Published - Apr 1 1982

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title = "Kinetic Studies on the O-Methylation of Dopamine by Human Brain Membrane-Bound Catechol O-Methyltransferase",

abstract = "Km values for dopamine and S-adenosylmethionine (AdoMet) of human brain membrane-bound catechol O-methyltransferase are 3.3 µM and 3.1 µM, respectively. S-Adenosylhomocysteine is a very potent competitive inhibitor with respect to AdoMet with a Ki value of 1 µM. 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 µM) 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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year = "1982",

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journal = "Biochemistry",

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T1 - Kinetic Studies on the O-Methylation of Dopamine by Human Brain Membrane-Bound Catechol O-Methyltransferase

AU - Rivett, A. Jennifer

AU - Roth, Jerome A.

PY - 1982/4/1

Y1 - 1982/4/1

N2 - Km values for dopamine and S-adenosylmethionine (AdoMet) of human brain membrane-bound catechol O-methyltransferase are 3.3 µM and 3.1 µM, respectively. S-Adenosylhomocysteine is a very potent competitive inhibitor with respect to AdoMet with a Ki value of 1 µM. 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 µM) 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.

AB - Km values for dopamine and S-adenosylmethionine (AdoMet) of human brain membrane-bound catechol O-methyltransferase are 3.3 µM and 3.1 µM, respectively. S-Adenosylhomocysteine is a very potent competitive inhibitor with respect to AdoMet with a Ki value of 1 µM. 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 µM) 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.

UR - https://www.scopus.com/pages/publications/0020320008

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DO - 10.1021/bi00537a006

M3 - Article

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AN - SCOPUS:0020320008

SN - 0006-2960

VL - 21

SP - 1740

EP - 1742

JO - Biochemistry

JF - Biochemistry

IS - 8

ER -

Kinetic Studies on the O-Methylation of Dopamine by Human Brain Membrane-Bound Catechol O-Methyltransferase

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