Sevanian A, Stein R A, Mead J F
Biochim Biophys Acta. 1980 Aug 7;614(2):489-500. doi: 10.1016/0005-2744(80)90238-7.
The activity of rat lung epoxide hydrolase (epoxide hydrolase, EC 3.3.2.3) was studied using two lipid epoxides which can be isolated from lung tissue. These epoxides displayed different Km,app and hydration rates. Methyl cis-9,10-epoxystearate was hydrated 20-times more rapidly than cholest-5 alpha,6 alpha-epoxy-3 beta-ol. The Km for the lung microsomal enzyme was variable and dependent on the microsome concentration in the medium. A soluble epoxide hydrolase was also detected in both lung and liver. This enzyme appears similar to the microsomal enzyme in its activity toward methyl epoxystearate. The measured activities for liver microsomal epoxide hydrolase were over 8-times those for lung microsomes; activity against cholesterol epoxide was 40-times greater for liver. In spite of the slow rates measured with cholesterol epoxide in lung preparations, this compound was an effective competitive inhibitor against methyl epoxystearate over a wide concentration range. This suggests that cholesterol epoxide readily binds to epoxide hydrolase and is an effective competitive inhibitor against a much more actively metabolized substrate, methyl epoxystearate. Such circumstances indicate that cholesterol epoxide binds with a high degree of nonproductivity to lung microsomal epoxide hydrolase. This attribute of lung epoxide hydrolase may relate to the relatively high concentrations of cholesterol epoxide found in lung tissue.
利用两种可从肺组织中分离得到的脂质环氧化物，对大鼠肺环氧化物水解酶（环氧化物水解酶，EC 3.3.2.3）的活性进行了研究。这些环氧化物表现出不同的表观米氏常数（Km,app）和水化速率。顺式-9,10-环氧硬脂酸甲酯的水化速度比胆甾-5α,6α-环氧-3β-醇快20倍。肺微粒体酶的Km是可变的，并且取决于培养基中微粒体的浓度。在肺和肝脏中还检测到一种可溶性环氧化物水解酶。该酶对环氧硬脂酸甲酯的活性似乎与微粒体酶相似。测得的肝脏微粒体环氧化物水解酶的活性比肺微粒体的活性高8倍以上；肝脏对胆固醇环氧化物的活性比对肺的活性高40倍。尽管在肺制剂中用胆固醇环氧化物测得的速率较慢，但在很宽的浓度范围内，该化合物是环氧硬脂酸甲酯的有效竞争性抑制剂。这表明胆固醇环氧化物很容易与环氧化物水解酶结合，并且是一种针对代谢更活跃的底物环氧硬脂酸甲酯的有效竞争性抑制剂。这种情况表明胆固醇环氧化物与肺微粒体环氧化物水解酶的结合具有高度的非生产性。肺环氧化物水解酶的这一特性可能与在肺组织中发现的相对较高浓度的胆固醇环氧化物有关。
