Immunochemical studies on the metabolism of nitrosamines by ethanol-inducible cytochrome P-450.
Immunochemical studies on the metabolism of nitrosamines by ethanol-inducible cytochrome P-450.
复制标题
乙醇诱导细胞色素 P-450 代谢亚硝胺的免疫化学研究。
DOI：
10.1016/0006-291x(85)90147-0
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发表时间：
1985
影响因子：
3.1
通讯作者：
Coon,MJ
中科院分区：
文献类型：
--
作者：
Yang,CS;Koop,DR;Wang,TY;Coon,MJ
乙醇诱导的兔肝微粒体细胞色素P-450，P-450 LM 3a，以前已被证明能有效地催化N-亚硝基二甲胺（NDMA）的去甲基化，Km为2.9 mM。由于乙醇处理的兔肝微粒体的主要Kmin为0.07 mM，P-450 LM 3a在激活这种致癌物质中的作用尚不确定。在本研究中，抗P-450 LM 3a的抗体几乎完全抑制重组系统中纯化的P-450的NDMA去甲基化以及对照或乙醇处理的兔肝微粒体的低Km活性。相反，抗体不抑制微粒体中的高KmNDMA脱甲基酶活性。这些结果表明，P-450 LM_3是导致KmNDMA脱甲基酶活性降低的主要P-450。此外，证据是存在的细胞色素的免疫化学类似于P-450 LM 3从大鼠，小鼠和豚鼠的肝微粒体，有效地催化NDMA的去甲基化。
The ethanol-induced rabbit liver microsomal cytochrome P-450, P-450LM3a, has been shown previously to efficiently catalyze the demethylation of N-nitrosodimethylamine (NDMA) with a Kmof 2.9 mM. Since the predominant Kmin hepatic microsomes from ethanol-treated rabbits is 0.07 mM, the role of P-450LM3ain the activation of this carcinogen has been uncertain. In the present study, antibodies to P-450LM3awere shown to almost completely inhibit NDMA demethylation by the purified P-450 in a reconstituted system as well as the low-Kmactivity of liver microsomes from control or ethanol-treated rabbits. In contrast, the antibody did not inhibit the high-KmNDMA demethylase activity in the microsomes. These results indicate that P-450LM3ais the major P-450 responsible for the low-KmNDMA demethylase activity. In addition, evidence is provided for the existence of a cytochrome immunochemically similar to P-450LM3ain liver microsomes from rats, mice, and guinea pigs that effectively catalyzes the demethylation of NDMA.