Cytochrome P-450 Interaction with Arachidonic Acid Hydroperoxides: Role in Lipid Peroxidation
The addition of the methyl ester of 15-hydroperoxyeicosa-5,8,11,13-tetraenoic acid, an arachidonic acid hydroperoxide, to rat liver microsomes results in the uptake of molecular oxygen and the formation of thiobarbituric acid reactive products, indicative of lipid peroxidation. Addition of the hydroperoxide to boiled microsomes does not lead to lipid peroxidation. Metyrapone and imidazole anti-mycotic agents, inhibitors of cytochrome P-450-dependent reactions, inhibit the initial rates of lipid peroxidation. The antioxidant butylated hydroxyanisole inhibits lipid peroxidation at a sub-stoichiometric concentration relative to the hydroperoxide, suggesting that the reaction is an autocatalytic free-radical process. The results indicate that microsomal cytochrome P-450 may play a role in the transformation of lipid hydroperoxides (such as those produced by the irradiation of membranes) to products of lipid peroxidation.
KeywordsLipid Peroxidation Methyl Ester Oxygen Uptake Liver Microsome Lipid Hydroperoxide
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