Metabolism of epoxidized phosphatidylcholine by phospholipase A2 and epoxide hydrolase.

The isolation and measurement of phospholipid epoxides as major peroxidation products in biomembrane preparations prompted an investigation of enzymatic mechanisms which may be responsible for their elimination. Analysis of microsomal epoxide hydrolase and phospholipase A2 activity against a phospholipid epoxide commonly encountered in tissues indicated it to be a poor substrate for epoxide hydrolase, but rapidly hydrolyzed by phospholipase A2. Microsomal and purified phospholipase A2 preparations hydrolyzed the phospholipid epoxide at rates 2-fold greater than were observed with a monoenoic phospholipid from which the epoxide would be derived. The product fatty acid epoxide, cis-9,10-epoxystearic acid, was rapidly hydrated by microsomal and cytosolic epoxide hydrolase. On the basis of earlier reports demonstrating increased phospholipase activity against oxidized phospholipids, and on the results of the present study, a model for the metabolism of oxidized membrane phospholipids is proposed.