Effect of inhibitors on omega- and (omega-1)-hydroxylation of lauric acid by frog liver microsomes.
To investigate the involvement of different cytochrome P-450 monooxygenases in fatty acid hydroxylation in frog liver microsomes, the effect of various inhibitors of cytochrome P-450 monooxygenases on the omega- and (omega-1)-hydroxylation of laurate was examined. The omega/omega-1-hydroxylation ratios were changed significantly by various levels of carbon monoxide (CO) inhibition; the formation of omega-hydroxylaurate was more sharply inhibited by various levels of CO than was the formation of (omega-1)-hydroxylaurate. On the contrary, metyrapone inhibited only the formation of (omega-1)-hydroxylaurate and stimulated the formation of omega-hydroxylaurate, 7,8-Benzoflavone as well as CO was more inhibitory to the omega-hydroxylation of laurate. At low concentrations of KCN (0.2 and 0.1 mM), the (omega-1)-hydroxylase activity was stimulated, but both the omega- and (omega-1)-hydroxylase activities were inhibited at the higher concentrations (5-10 mM). The effect of drugs and hydroxylaurate isomers on the omega- and (omega-1)-hydroxylation was also examined. Aminopyrine showed a stimulative effect on omega-hydroxylase activity and no effect on the (omega-1)-hydroxylase activity, while p-nitroanisole inhibited the (omega-1)-hydroxylase activity and showed almost no effect on the omega-hydroxylase activity. 12-Hydroxylaurate inhibited both the omega- and (omega-1)-hydroxylase activities, but the omega-hydroxylase activity was inhibited to a much greater extent. 11-Hydroxylaurate had no effect on either hydroxylation. These findings strongly support the hypothesis that different cytochrome P-450 species are involved in the hepatic microsomal hydroxylation of laurate at omega- and (omega-1)-positions in the frog.
D000632:Aminopyrine / Q000494:pharmacology; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D007850:Lauric Acids / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011190:Potassium Cyanide / Q000494:pharmacology; D011892:Rana catesbeiana
D000840:Anisoles; D007850:Lauric Acids; D000632:Aminopyrine; C030358:lauric acid; D006899:Mixed Function Oxygenases; C005306:4-nitroanisole; D011190:Potassium Cyanide