ROLE OF GLUTATHIONE-PEROXIDASE AND PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE IN THE REDUCTION OF LYSOPHOSPHOLIPID HYDROPEROXIDES

1-linoleoyl lysophosphatidylcholine hydroperoxide is a substrate of GS H peroxidase (GPx) both purified from bovine erythrocytes and nonpurif ied from rat liver. The initial reaction rate for bovine erythrocyte G Px with l-linoleoyl lysophosphatidylcholine hydroperoxide is about 76 and 95% of the reaction rate for hydrogen peroxide and linoleic acid h ydroperoxide respectively. For rat liver GPx these initial reaction ra tes are about 66 and 75%, respectively. The rate constants for the rea ction of GPx with 1-linoleoyl lysophosphatidylcholine hydroperoxide we re calculated to be similar to 3 x 10(7) M(-1)s(-1) and similar to 2 x 10(6) M(-1)s(-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 hydropero xides in vivo is the peroxidation of lysophospholipids, both in mitoch ondrial inner membranes and in endoplasmic reticulum; (2) a specialize d enzyme able to reduce directly lysophospholipid hydroperoxides is im portant for the reduction of these hydroperoxides, because the detoxif ication of these species mediated by the action of acyl ester bond cle aving enzymes is not efficient; (3) the reduction through GPx predomin ates over phospholipid hydroperoxide glutathione peroxidase (PHGPx) in mitochondrial inner membranes and in the cytosolic phase of the endop lasmic reticulum; (4) in the luminal phase of endoplasmic reticulum PH GPx is predominant. Copyright (C) 1997 Elsevier Science Inc.