Differential substrate selectivity of murine hepatic cytosolic and microsomal epoxide hydrolases.
Differential substrate selectivity of murine hepatic cytosolic and microsomal epoxide hydrolases.
复制标题
鼠肝胞质和微粒体环氧化物水解酶的不同底物选择性。
DOI：
10.1016/0006-2952(83)90264-2
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发表时间：
1983
影响因子：
5.8
通讯作者：
Hasagawa,LS
中科院分区：
文献类型：
--
作者：
Hammock,BD;Hasagawa,LS
在小鼠肝脏的胞质和微粒体组分的存在下，测定了十六种环氧化物的初始水合速率。发现1，2-二取代反式环氧化物是胞质环氧化物水解酶的优良的选择性底物，而当一个或多个取代基是苯基部分时，1，2-顺式环氧化物的水合性差。环氧化物的环状系统，包括苯并[a]芘4，5-氧化物，和两个环二烯类似物水合几乎完全由微粒体环氧化物水解酶，而单取代的环氧化物水合由两个系统。一些环氧化物，这是平庸的底物被证明是合理的抑制剂的胞质环氧化物水解酶，表明底物结合和营业额的结构要求是不同的。一些已知与巯基相互作用的试剂，包括氧化苯乙烯，被证明是良好的抑制剂。这项工作有利于设计的放射化学和分光光度法测定两种主要形式的环氧化物水解酶以及潜在的内在底物的预测。此外，这些数据可能对评估人类接触环氧化异生物质的风险有意义。
The initial rates of hydration of sixteen epoxides in the presence of cytosolic and microsomal fractions of mouse liver were determined. 1,2-Disubstitutedtrans-epoxides were found to be excellent, selective substrates for the cytosolic epoxide hydrolase, while 1,2-cis-epoxides were poorly hydrated when one or more substituents was a phenyl moiety. Epoxides of cyclic systems including benzo[a]pyrene 4,5-oxide, and two cyclodiene analogs were hydrated almost exclusively by the microsomal epoxide hydrolase while monosubstituted epoxides were hydrated by both systems. Some epoxides which were mediocre substrates proved to be reasonable inhibitors of the cytosolic epoxide hydrolase, indicating that the structural requirements for substrate binding and turnover are different. Some reagents known to interact with sulfhydryl groups, including styrene oxide, proved to be good inhibitors. This work facilitates the design of radiochemical and spectrophotometric assays for both major forms of epoxide hydrolase as well as prediction of potential intrinsic substrates. Also such data may be meaningful in assessing the risk involved in human exposure to epoxidized xenobiotics.