ω-1 and ω-2 hydroxylation of prostaglandins by rabbit hepatic microsomal cytochrome P-450 isozyme 6

Incubation of prostaglandin E₁ (PGE₁) with liver microsomes from control rabbits and from rabbits treated with ethanol or imidazole yielded 18-, 19-, and 20-hydroxy metabolites, representing hydroxylation at ω-2, ω-1, and ω carbons, respectively. The current investigation demonstrates that rabbit liver P-450 isozyme 6 effectively catalyzes the ω-1 andg w-2 hydroxylation of PGE₁ and PGE₂. Additionally, a small amount of product with Chromatographic characteristics of the corresponding 20-hydroxy metabolite has been detected. The incorporation of cytochrome b₅ into the reconstituted system did not enhance the rate of PGE₁ hydroxylation and had no effect on the ratio of products formed. The K_m value for the ω-1 and ω-2 hydroxylation of PGE₁ with P-450 isozyme 6 from imidazole-treated rabbits was approximately 140 μm; the V_max's (nmol product min^-1 nmol P-450^-1) were 2.1 and 1.1 for the ω-1 and ω-2 hydroxylations, respectively. These rates represent the highest activities by hepatic P-450 isozymes for hydroxylation of PGs, and suggest that isozyme 6 is responsible for the ω-2 hydroxylation of PGEs observed in rabbit liver microsomes.