Chang T, Levine M, Bellward G D
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Can J Physiol Pharmacol. 1990 Dec;68(12):1510-3. doi: 10.1139/y90-229.
To study the regulation of the multiple forms of erythromycin N-demethylase, we determined the influence of sex and inducer treatment on this mixed-function oxidase activity in adult Wistar rats injected intraperitoneally once daily for 4 days with dexamethasone, pregnenolone-16 alpha-carbonitrile, phenobarbital, or 2% Tween 80 (control). Based on the results from a computer curve-fitting procedure (ENZFITTER) as well as Eadie-Hofstee and Lineweaver-Burk plots, at least two forms of erythromycin N-demethylase were present in control, dexamethasone, pregnenolone-16 alpha-carbonitrile, and phenobarbital-treated male rats and in control and dexamethasone-treated female rats. Only a high-affinity form was apparent in pregnenolone-16 alpha-carbonitrile and phenobarbital-treated female rats. Therefore, more than one form of erythromycin N-demethylase exists in hepatic microsomes from adult rats, depending on sex and inducer treatment. As well, at a substrate concentration commonly used in the erythromycin N-demethylase assay, the relative contribution of the high- and low-affinity forms to the enzyme activity varies with sex and inducer treatment.
为研究红霉素N - 脱甲基酶多种形式的调控机制，我们测定了性别及诱导剂处理对成年Wistar大鼠混合功能氧化酶活性的影响。将大鼠每日腹腔注射地塞米松、孕烯醇酮 - 16α - 腈、苯巴比妥或2%吐温80（对照），持续4天。基于计算机曲线拟合程序（ENZFITTER）以及伊迪 - 霍夫斯泰因和林恩韦弗 - 伯克作图法的结果，在对照、地塞米松、孕烯醇酮 - 16α - 腈和苯巴比妥处理的雄性大鼠以及对照和地塞米松处理的雌性大鼠中，至少存在两种形式的红霉素N - 脱甲基酶。在孕烯醇酮 - 16α - 腈和苯巴比妥处理的雌性大鼠中，仅有一种高亲和力形式明显。因此，成年大鼠肝微粒体中存在不止一种形式的红霉素N - 脱甲基酶，这取决于性别和诱导剂处理。同样，在红霉素N - 脱甲基酶测定常用的底物浓度下，高亲和力和低亲和力形式对酶活性的相对贡献随性别和诱导剂处理而变化。
