Role of Glutathione Peroxidase and Phospholipid Hydroperoxide Glutathione Peroxidase in the Reduction of Lysophospholipid Hydroperoxides

1-linoleoyl lysophosphatidylcholine hydroperoxide is a substrate of GSH peroxidase (GPx) both purified from bovine erythrocytes and nonpurified from rat liver. The initial reaction rate for bovine erythrocyte GPx with 1-linoleoyl lysophosphatidylcholine hydroperoxide is about 76 and 95% of the reaction rate for hydrogen peroxide and linoleic acid hydroperoxide respectively. For rat liver GPx these initial reaction rates are about 66 and 75%, respectively. The rate constants for the reaction of GPx with 1-linoleoyl lysophosphatidylcholine hydroperoxide were calculated to be not, vert, similar3 × 107 M−1s−1 and not, vert, similar2 × 106 M−1s−1 for the bovine erythrocyte and the rat liver enzymes, respectively. By using kinetic models of lipid peroxidation we found by simulation that: (1) the main source of lysophospholipid hydroperoxides in vivo is the peroxidation of lysophospholipids, both in mitochondrial inner membranes and in endoplasmic reticulum; (2) a specialized enzyme able to reduce directly lysophospholipid hydroperoxides is important for the reduction of these hydroperoxides, because the detoxification of these species mediated by the action of acyl ester bond cleaving enzymes is not efficient; (3) the reduction through GPx predominates over phospholipid hydroperoxide glutathione peroxidase (PHGPx) in mitochondrial inner membranes and in the cytosolic phase of the endoplasmic reticulum; (4) in the luminal phase of endoplasmic reticulum PHGPx is predominant. Copyright © 1997 Elsevier Science Inc.