Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by alpha-naphthoflavone.
Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by alpha-naphthoflavone.
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发表时间：
1988-05
影响因子：
3.6
通讯作者：
G. Schwab;J. Raucy;Eric F. Johnson
中科院分区：
文献类型：
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作者：
G. Schwab;J. Raucy;Eric F. Johnson
利福平诱导兔肝微粒体细胞色素P-450 3c、孕酮16 α-和6 β-羟基化、17 β-雌二醇2-羟基化、苯并[a]芘羟基化和红霉素N-去甲基化。由利福平处理的B/J家兔制备的肝微粒体催化的孕酮6 β-羟基化的动力学分析显示出曲线双倒数图，表明底物活化。进一步的实验表明，α-萘醌可以增加对孕酮的16 α-和6 β-羟基化以及17 β-雌二醇的2-羟基化观察到的催化效率[Vmax/Km]，而红霉素N-脱甲基酶活性被部分抑制。在人肝微粒体中也发现了α-萘酚酮对这些类固醇羟化酶的变构激活，表明这些酶的激活在人和兔中是保守的。
Rifampicin induces cytochrome P-450 3c, progesterone 16 alpha- and 6 beta-hydroxylation, 17 beta-estradiol 2-hydroxylation, benzo[a] pyrene hydroxylation, and erythromycin N-demethylation in rabbit liver microsomes. Kinetic analysis of the 6 beta-hydroxylation of progesterone as catalyzed by liver microsomes prepared from rifampicin-treated B/J rabbits exhibits a curvilinear double-reciprocal plot, suggestive of substrate activation. Further experimentation demonstrated that alpha-naphthoflavone could augment the catalytic efficiency [Vmax/Km] observed for the 16 alpha- and 6 beta-hydroxylation of progesterone and the 2-hydroxylation of 17 beta-estradiol, whereas erythromycin N-demethylase activity was partially inhibited. Allosteric activation of these steroid hydroxylases by alpha-naphthoflavone is also found for human liver microsomes, indicating that the activation of these enzymes is conserved in man and rabbit.