METABOLISM OF HYDROPEROXY-PHOSPHOLIPIDS IN HUMAN HEPATOMA HEPG2 CELLS

Two enzymatic mechanisms have been proposed for the metabolism of hydr operoxy-phospholipids: i) the combined action of phospholipase A? and glutathione peroxidase, and/or ii) direct enzymatic reduction. The lat ter reaction may be catalyzed by selenium-dependent phospholipid hydro peroxide glutathione peroxidase and/or by glutathione S-transferase al pha. To study the pathway of this reaction, we used human hepatoma Hep G2 cells into which was incorporated labeled, hydroperoxy-phospholipid s. The major product of incorporated 1-palmitoyl-2-(13-hydroperoxy-cis -9,trans-1 1-octadecadienoyl)-L-3-phosphatidylcholine was the correspo nding hydroxy-phospholipid with no hydroxy- or hydroperoxy-fatty acids . The contributions to reduction of hydroperoxy-phospholipids in HepG2 cells from glutathione S-transferase A1 and phospholipid hydroperoxid e glutathione peroxidase were calculated to be 0.5% and 99.5%, respect ively. Increasing selenium in the cell culture medium led to increases in selenium-dependent phospholipid hydroperoxide glutathione peroxida se activity but not in glutathione S-transferase alpha. This increase in the selenium-dependent enzyme was paralleled by a concomitant incre ase in the extent of reduction of the incorporated hydroperoxy-phospho lipid. We conclude that the main metabolic fate of hydroperoxy-phospho lipids in HepG2 cells is by direct reduction to hydroxy-phospholipids by phospholipid hydroperoxide glutathione peroxidase but also by gluta thione S-transferase alpha, and that phospholipase A(2)/selenium-depen dent glutathione peroxidase does not play a significant role in the re duction.