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兔肺单加氧酶系统。酶成分的免疫化学和生物化学特性

The rabbit pulmonary monooxygenase system. Immunochemical and biochemical characterization of enzyme components.

作者信息

Serabjit-Singh C J, Wolf C R, Philpot R M

出版信息

J Biol Chem. 1979 Oct 10;254(19):9901-7.

PMID:114516
Abstract

The enzymatic components of the rabbit pulmonary monooxygenase system, cytochromes P-450I and P-450II and NADPH-cytochrome P-450 reductase, are immunochemically distinct proteins. In pulmonary microsomes, the N-demethylation of benzphetamine, amino-pyrine, and ethylmorphine, and the O-deethylation of 7-ethoxycoumarin are dependent only on cytochrome P-450I, and the hydroxylation of coumarin is apparently catalyzed by both cytochromes. Cytochrome P-450II is immunochemically distinct from the major forms of hepatic cytochrome P-450 induced by phenobarbital or 3-methylcholanthrene, whereas cytochrome P-450I is indistinguishable from the former on the basis of physical and catalytic as well as immunochemical characteristics. Pulmonary and hepatic NADPH-cytochrome P-450 reductases also have identical physical, catalytic, and immunochemical properties. The lack of response of the lung monooxygenase system to phenobarbital, therefore, is apparently not due to an inability of the lung to synthesize the enzymes induced by phenobarbital in the liver. The relatively high proportion of cytochrome P-450I in the lung appears to be responsible for the higher rates (per nmol of P-450) of N-demethylation that have been observed in rabbit pulmonary as compared to hepatic microsomal fractions.

摘要

兔肺单加氧酶系统的酶成分,即细胞色素P - 450I、细胞色素P - 450II和NADPH - 细胞色素P - 450还原酶,是免疫化学上不同的蛋白质。在肺微粒体中,苄非他明、氨基比林和乙基吗啡的N - 去甲基化,以及7 - 乙氧基香豆素的O - 去乙基化仅依赖于细胞色素P - 450I,而香豆素的羟基化显然由两种细胞色素催化。细胞色素P - 450II在免疫化学上与苯巴比妥或3 - 甲基胆蒽诱导的肝细胞色素P - 450的主要形式不同,而细胞色素P - 450I在物理、催化以及免疫化学特性方面与前者无法区分。肺和肝的NADPH - 细胞色素P - 450还原酶在物理、催化和免疫化学性质上也相同。因此,肺单加氧酶系统对苯巴比妥缺乏反应显然不是由于肺无法合成肝脏中由苯巴比妥诱导的酶。与肝微粒体部分相比,肺中细胞色素P - 450I的相对高比例似乎是兔肺中观察到的较高N - 去甲基化速率(每nmol P - 450)的原因。

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