Effect of phenobarbital treatment and cytochrome P-450 inhibitors on the laurate omega- and (omega - 1)-hydroxylase activities of rat liver microsomes.
Effect of phenobarbital treatment and cytochrome P-450 inhibitors on the laurate omega- and (omega - 1)-hydroxylase activities of rat liver microsomes.
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苯巴比妥治疗和细胞色素 P-450 抑制剂对大鼠肝微粒体月桂酸 omega- 和 (omega-1)-羟化酶活性的影响。
DOI：
10.1124/dmd.8.3.147
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
B. Masters
中科院分区：
文献类型：
--
作者：
R. Okita;B. Masters
研究了大鼠肝微粒体中月桂酸的omega-和(omega-1)-羟基酶活性。用苯巴比妥处理大鼠，选择性地诱导脂肪酸(omega-1)羟化反应活性增加2~3倍，但对omega-羟化反应影响不大。SKF 525-A、甲孕酮和α-萘黄酮对(omega-1)-羟化有抑制作用，但对omega-羟化无明显影响。浓度为10(-4)的甲孕酮对苯巴比妥处理的大鼠的(omega-1)-羟化酶比活力抑制70%，但对omega-羟化活性的抑制仅为10%。在10(-4)M浓度下，α-萘黄酮对未处理和β-胡椒黄酮预处理大鼠的(omega-1)羟基酶活性抑制60%，而omega-羟基酶活性仅降低20%。当微粒体于4℃下保存过夜时，也观察到了选择性效应，24小时和48小时后，(omega-1)-羟基酶活性分别下降了50%和70%，而omega-羟化仅下降了10%-20%。不同条件对omega-和(omega-1)-羟基酶活性的不同影响表明，不同的细胞色素P-450介导了肝微粒体中的这两种脂肪酸羟基酶。
The omega- and (omega - 1)-hydroxylase activities for lauric acid were investigated in rat liver microsomes. Treatment of rats with phenobarbital selectively induced the hydroxylation of the fatty acid (omega - 1)-hydroxylase activity two- to threefold, but had little effect on the omega-hydroxylation reaction. SKF 525-A, metyrapone, and alpha-naphthoflavone inhibited (omega - 1)-hydroxylation, but had only neglible effects on omega-hydroxylation. Metyrapone at 10(-4) inhibited the specific activity of (omega - 1)-hydroxylase 70% in phenobarbital-pretreated rats, but produced only a 10% inhibition of the omega-hydroxylation activity. alpha-Naphthoflavone at 10(-4)M inhibited (omega - 1)-hydroxylase activity 60% in untreated and beta-haphthoflavone-pretreated rats, while omega-hydroxylase activity was decreased only 20%. A selective effect was also observed when microsomes were stored overnight at 4 degrees C. Declines of 50% and 70% were observed in the (omega - 1)-hydroxylase activities after 24 and 48 hr, respectively, whereas omega-hydroxylation decreased only 10-20%. The differential effects on omega- and (omega - 1)-hydroxylase activities of a variety of conditions suggest that distinct cytochromes P-450 mediate the two fattty acid hydroxylases in liver microsomes.