Effects of lipid peroxidation on the activity of microsomal UDPglucuronosyltranserase.

This study is concerned with effects of lipid peroxidation of liver microsomal fractions in vitro on the activity of the membrane-dependent enzyme UDPglucuronosyltransferase. Peroxidation was initiated by the ascorbate-Fe2+ redox couple. Peroxidation had a biphasic effect on transferase activity (with p-nitrophenol or o-aminophenol as acceptors). An initial activation at low levels of peroxidation was followed by inactivation after more prolonged peroxidation. Activation was more pronounced with rat preparations than with those from guinea pig. When taken in conjunction with previous work on the effects of membrane perturbants on transferase activity the results indicate that activation was the result of membrane perturbation, probably resulting from shortening of phospholipid hydrocarbon chains. The inactivation of the enzyme in guinea pig liver microsomal preparations was not reversed by adding phospholipids. It is concluded that the irreversible inactivation was probably due to chemical reaction of intermediate products of peroxidation with essential membrane components, possibly the enzyme itself. Further experiements suggested that lipid peroxides were responsible.