苯巴比妥治疗及细胞色素P-450抑制剂对大鼠肝微粒体月桂酸ω-和（ω-1）-羟化酶活性的影响。

Effect of phenobarbital treatment and cytochrome P-450 inhibitors on the laurate omega- and (omega - 1)-hydroxylase activities of rat liver microsomes.

作者信息

Okita R T, Masters B S

出版信息

Drug Metab Dispos. 1980 May-Jun;8(3):147-51.

Abstract

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.

摘要

在大鼠肝微粒体中研究了月桂酸的ω-羟化酶和（ω-1）-羟化酶活性。用苯巴比妥处理大鼠可选择性地使脂肪酸（ω-1）-羟化酶活性的羟基化增加2至3倍，但对ω-羟化反应影响很小。SKF 525-A、甲吡酮和α-萘黄酮抑制（ω-1）-羟化，但对ω-羟化只有微不足道的影响。在苯巴比妥预处理的大鼠中，10^(-4)浓度的甲吡酮抑制（ω-1）-羟化酶的比活性70%，但对ω-羟化活性仅产生10%的抑制。10^(-4)M浓度的α-萘黄酮在未处理和β-萘黄酮预处理的大鼠中抑制（ω-1）-羟化酶活性60%，而ω-羟化酶活性仅降低20%。当微粒体在4℃下储存过夜时也观察到了选择性效应。分别在24小时和48小时后，（ω-1）-羟化酶活性下降了50%和70%，而ω-羟化仅下降10%-20%。各种条件对ω-羟化酶和（ω-1）-羟化酶活性的不同影响表明，不同的细胞色素P-450介导肝微粒体中的两种脂肪酸羟化酶。