细胞色素P450 2 e1和3都参与p-nitrophenol O-hydroxylation,催化活性已知特定P450 2 e1。
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卢卡斯Zerilli, Ratanasavanh D, D, Goasduff T, Dreano Y, Menard C, Picart D, Berthou F
细胞色素P450 2 e1和3都参与p-nitrophenol O-hydroxylation,催化活性已知特定P450 2 e1。
化学Res Toxicol。10月1997;10(10):1205 - 12所示。
- PubMed ID
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9348445 (在PubMed]
- 文摘
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4-Nitrophenol 2-hydroxylation活动以前是主要催化P450 2 e1在动物和人类。这种化合物被广泛的用作体外探针P450 2 e1,这项研究其催化特异性进行了测试。首先,进行实验治疗的大鼠肝微粒体和肝细胞文化不同的诱导物。肝微粒体吡唑-和dexamethasone-treated老鼠羟化p-nitrophenol代谢率增加了2.5和2.7倍和控制。地塞米松治疗肝P450含量增加3但不是P450 2 e1。两个特定抑制剂P450 3催化活动,也就是说,酮康唑和troleandomycin(道),抑制50%的4-nitrophenol羟基化在dexamethasone-treated老鼠而不是控制。肝细胞培养dexamethasone-treated老鼠p-nitrophenol变成4-nitrocatechol 7.8倍的控制。这道催化活性被抑制。同样,从pyrazole-treated大鼠肝细胞文化羟化p-nitrophenol与vs控制代谢率增加了8倍。二乙基二硫代氨基甲酸反应被抑制,二甲亚砜,P450 2 e1的抑制剂。 Second, the capability of human P450s other than P450 2E1 to catalyze the formation of 4-nitrocatechol was examined in a panel of 13 human liver microsomes. Diethyl dithiocarbamate and ketoconazole reduced 4-nitrophenol hydroxylase activity by 77% (+/- 11) and 13% (+/- 16), respectively. Furthermore, the residual activity following diethyl dithiocarbamate inhibition was significantly correlated with seven P450 3A4 catalytic activities. Finally, the use of human cell lines genetically engineered for expression of human P450s demonstrated that P450 2E1 and 3A4 hydroxylated 4-nitrophenol with turnovers of 19.5 and 1.65 min-1, respectively. In conclusion, P450 3A may make a significant contribution to 4-nitrophenol hydroxylase activity in man and rat.