OMEGA-HYDROXYLATION AND (OMEGA-1)-HYDROXYLATION OF ARACHIDONIC-ACID, LAURIC ACID AND PROSTAGLANDIN-A1 BY MULTIPLE FORMS OF CYTOCHROME-P-450 PURIFIED FROM RAT HEPATIC MICROSOMES

The metabolism of arachidonic acid, lauric acid and prostaglandin A1 by rat hepatic microsomes and multiple forms of cytochrome P-450 purified from rat hepatic microsomes was studied. Arachidonic acid was hydroxylated by hepatic microsomes of male rats by ω- and (ω - 1)-hydroxylation. Phenobarbital treatment of rats decreased the hydroxylation activity slightly, but 3-methylcholanthrene treatment increased the hydroxylation activity 2-fold. However, lauric acid and prostaglandin A1 ω- and ω - 1)-hydroxylation activities decreased after treatment with phenobarbital and 3-methylcholanthrene. Arachidonic acid and lauric acid were metabolized with similar ratios of ω- and (ω - 1)-hydroxylation, but prostaglandin A1 was efficiently metabolized at the ω-position by hepatic microsomes of untreated male rats. In a reconstituted system with purified cytochromes P-450, P-450 UT-1, UT-2 (P-450h), MC-1 (P-450d) and MC-5 (P-450c) effectively hydroxylated arachidonic acid at both the ω- and (ω - 1)-position. P-450 UT-8 hydroxylated arachidonic acid only at the ω-position. P-450 DM (P-450J) hydroxylated arachidonic acid at the (ω-1)-position efficiently. Lauric acid was also hydroxylated by P-450 UT-1, UT-2, PB-1, PB-2, MC-1, IF-3 (P-450a) and DM, at the (ω-1)-position only. Only P-450 UT-8 could hydroxylate lauric acid at the ω-position. Prostaglandin A1 was efficiently and specifically metabolized by P-450 UT-8 with ω-hydroxylation. P-450 UT-2 and PB-1 could hydroxylate prostaglandin A1 by (ω - 1)-hydroxylation, but with low activity. © 1990.