Selective inhibition and selective induction of multiple microsomal epoxide hydrolases.
Selective inhibition and selective induction of multiple microsomal epoxide hydrolases.
复制标题
多种微粒体环氧化物水解酶的选择性抑制和选择性诱导。
DOI：
10.1016/0006-2952(86)90253-4
复制
发表时间：
1986
影响因子：
5.8
通讯作者：
Guenthner,TM
中科院分区：
文献类型：
--
作者：
Guenthner,TM
对微粒体反式二苯乙烯氧化物水解酶的体外抑制和体内诱导进行了研究。该微粒体环氧化物水解酶活性可通过许多催化标准与先前明确定义的微粒体芳烃氧化物水解酶区分开。两种取代的查尔酮氧化物4-苯基查尔酮氧化物和4 ′-苯基查尔酮氧化物是微粒体反式二苯乙烯氧化物水解酶的有效抑制剂，但对苯并[a]芘4，5-氧化物水解酶无明显活性。相反，作为苯并[a]芘4，5-氧化物水解酶的有效抑制剂的化合物，包括氧化苯乙烯、氧化环己烯和氧化三氯丙烯，仅在非常高的（毫摩尔）浓度下抑制微粒体反式二苯乙烯氧化物水解酶。查尔酮氧化物抑制microsomaltrans-stilbene氧化物水解酶非竞争性，并具有微摩尔或纳摩尔的酶的亲和常数。尝试在体内诱导微粒体反式二苯乙烯氧化物水解酶。在小鼠中诱导微粒体苯并[a]芘4，5-氧化物水解酶水平的化合物不同时诱导反式-二苯乙烯氧化物水解酶水平。氯贝特是一个例外，它诱导的两种酶的水平，以一个小的，但统计学显着的程度。因此，这两种微粒体水解酶活性具有非常不同的催化位点，并且似乎受到单独的遗传控制。4-苯基查尔酮氧化物和4 ′-苯基查尔酮氧化物是微粒体反式-二苯乙烯氧化物水解酶的选择性抑制剂，并可能被证明是非常有用的评估这种酶参与内源性或外源性环氧化物的代谢。
The inhibitionin vitroand inductionin vivoof microsomaltrans-stilbene oxide hydrolase have been studied. This microsomal epoxide hydrolase activity is distinguishable from the previously well-defined microsomal arene oxide hydrolase by a number of catalytic criteria. Two substituted chalcone oxides, 4-phenylchalcone oxide and 4′-phenylchalcone oxide, are potent inhibitors of microsomaltrans-stilbene oxide hydrolase, but have no apparent activity against benzo[a]pyrene 4,5-oxide hydrolase. Conversely, compounds that are potent inhibitors of benzo[a]pyrene 4,5-oxide hydrolase, including styrene oxide, cyclohexene oxide, and trichloropropene oxide, inhibit microsomal transstilbene oxide hydrolase only at very high (millimolar) concentrations. The chalcone oxides inhibit microsomaltrans-stilbene oxide hydrolase noncompetitively, and have micromolar or nanomolar affinity constants for the enzyme. Attempts were made to induce microsomaltrans-stilbene oxide hydrolasein vivo. Compounds that induced microsomal benzo[a]pyrene 4,5-oxide hydrolase levels in mice did not simultaneously inducetrans-stilbene oxide hydrolase levels. Clofibrate was an exception; it induced levels of both enzymes to a small but statistically significant degree. The two microsomal hydrolase activities have, therefore, very different catalytic sites and appear to be under separate genetic control. 4-Phenylchalcone oxide and 4′-phenylchalcone oxide are selective inhibitors of microsomaltrans-stilbene oxide hydrolase and may prove to be very useful in assessing the involvement of this enzyme in the metabolism of endogenous or xenobiotic epoxides.