Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid.

Abstract

Arachidonic acid is oxidatively metabolized by rat liver microsomes at a rate of .apprx. 5 nmol/min per mg of protein at 25.degree. C. This reaction is dependent on the presence of NADPH and O2. Studies with various inhibitors indicate a role for membrane-bound cytochrome P-450 in the transformation of arachidonic acid to a mixture of hydroxy acid derivatives. The stoichiometry of the reaction conforms to that of a monooxygenase reaction i.e., 1 mol of NADPH is oxidized per mole of O2 utilized suggesting a reaction mechanism different from that proposed for lipid peroxidation reactions. No evidence for the formation of prostaglandin-like metabolites was obtained. The diene character of some of the metabolites formed suggests another role for cytochrome P-450, i.e., participation in hydrogen abstraction reactions for the activation of various substrates.