人脑膜结合儿茶酚-O-甲基转移酶对多巴胺O-甲基化的动力学研究。

Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase.

作者信息

Rivett A J, Roth J A

出版信息

Biochemistry. 1982 Apr 13;21(8):1740-2. doi: 10.1021/bi00537a006.

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.

摘要

人脑膜结合型儿茶酚-O-甲基转移酶对多巴胺和S-腺苷甲硫氨酸（AdoMet）的米氏常数分别为3.3微摩尔和3.1微摩尔。S-腺苷同型半胱氨酸是一种对AdoMet非常有效的竞争性抑制剂，其抑制常数（Ki）值为1微摩尔。产物抑制模式有力地支持了一种稳态强制顺序三元复合物机制，即AdoMet在多巴胺之前与酶结合。托酚酮对膜结合型儿茶酚-O-甲基转移酶的抑制作用对多巴胺而言是竞争性的（Ki = 5微摩尔），对AdoMet而言是非竞争性的，这与这种机制类型相符。所提出的机制与可溶性儿茶酚-O-甲基转移酶的机制不同。