Nonenzymatically evoked and cytochrome P450-dependent lipid peroxidation inhibits synthesis of phosphatidylethanolamine via the ethanolamine base exchange reaction in rat liver microsomes

Abstract

In the present study the relationship between lipid peroxidation, changes in the redox state of membrane and phosphatidylethanolamine (PE) synthesis via base exchange reaction in rat liver microsomes was investigated. It was found that PE synthesis is enhanced in the presence of antioxidants, butylated hydroxytoluene (BHT), or unsaturated free fatty acids. Prooxidants, tert-butyl hydroxyperoxide (BHP), ferrous ions combined with ascorbate or NADPH (via cytochrome P450-dependent proteins), increased the amount of lipid peroxidation products in the membrane, and in consequence inhibited the reaction. The effect of BHP was fully reversed by reduced glutathione and dithiothreitol (DTT), whereas the effect of other compounds could be reversed only by BHT. In contrast, a reversal of the inhibitory effect of cadmium ions on base exchange activity was observed in the presence of DTT, but not BHT. Therefore, both the -SH/-S-S- ratio in the membrane, affected by BHP and cadmium ions, and the lipid hydroxyperoxides (rather than aldehydes), generated by ferrous ions and ascorbate or NADPH, are equally responsible for the inactivation of the ethanolamine base exchange enzyme in rat liver microsomes. This may suggest that the synthesis of PE via the base exchange reaction may be considered an element of the superfine cellular machinery involved in the repair of damage to unsaturated fatty acid chains of phospholipids caused by reactive oxygen species under oxidative stress.