肝微粒体N-氧化形成机制的研究。细胞色素P-450和混合功能胺氧化酶在N,N-二甲基苯胺N-氧化中的作用。
Studies on the mechanism of hepatic microsomal N-oxide formation. The role of cytochrome P-450 and mixed-function amine oxidase in the N-oxidation of NN-dimethylaniline.
作者信息
Hlavica P, Kehl M
出版信息
Biochem J. 1977 Jun 15;164(3):487-96. doi: 10.1042/bj1640487.
Abstract
Evidence is established for the existence of alternative metabolic routes of N-oxidation of NN-dimethylaniline in rabbit liver microsomal fraction. One pathway involves the participation of two types of cytochrome P-450 with different sensitivities towards heat. Both types may represent distinct haemoprotein species or two physical forms of a single pigment. The other pathway is represented by the mixed-function amine oxidase. The enzyme lacks NADPH dehydrogenase activity and is insensitive to treatment with 2-bromo-4'-nitroacetophenone and steapsin: it catalyses N-oxidation of imipramine, trimethylamine and NN-dimethylaniline in molar proportions considerably different from those of the cytochrome P-450-supported reactions. Cytochrome P-450 is estimated to account for the formation of at least 50-60% of the total NN-dimethylaniline N-oxide formed in the intact rabbit liver microsomal fraction, the remainder arising from the action of the mixed-function amine oxidase.
摘要
已证实兔肝微粒体部分中存在NN-二甲基苯胺N-氧化的替代代谢途径。一条途径涉及两种对热敏感度不同的细胞色素P-450的参与。这两种类型可能代表不同的血红蛋白种类或单一色素的两种物理形式。另一条途径由混合功能胺氧化酶代表。该酶缺乏NADPH脱氢酶活性，对2-溴-4'-硝基苯乙酮和胰脂肪酶处理不敏感：它催化丙咪嗪、三甲胺和NN-二甲基苯胺的N-氧化，其摩尔比例与细胞色素P-450支持的反应有很大不同。据估计，细胞色素P-450在完整兔肝微粒体部分中形成的总NN-二甲基苯胺N-氧化物中至少占50-60%，其余部分由混合功能胺氧化酶的作用产生。
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