EFFECT OF PHENOBARBITAL TREATMENT AND CYTOCHROME-P-450 INHIBITORS ON THE LAURATE OMEGA-HYDROXYLASE AND (OMEGA - 1)-HYDROXYLASE ACTIVITIES OF RAT-LIVER MICROSOMES

  • 1 January 1980
    • journal article
    • research article
    • Vol. 8  (3) , 147-151
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 2- to 3-fold, but had little effect on the .omega.-hydroxylation reaction. SKF 525-A [proadifen hydrochloride], metyrapone and .alpha.-naphthoflavone inhibited (.omega. - 1)-hydroxylation, but had only negligible 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.-naphthoflavone-pretreated rats, while .omega.-hydroxylase activity was decreased only 20%. A selective effect was observed when microsomes were stored overnight at 4.degree. C. Decline of 50 and 70% were observed in the (.omega. - 1)-hydroxylase activities after 24 and 48 h, respectively, but .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 2 fatty acid hydroxylases in liver microsomes.