Marinho H S, Antunes F, Pinto R E
Departamento de Quimica e Bioquimica, Faculdade de Ciências, Universidade de Lisboa, Portugal.
Free Radic Biol Med. 1997;22(5):871-83. doi: 10.1016/s0891-5849(96)00468-6.
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 approximately 3 x 10(7) M-1s-1 and approximately 2 x 10(6) 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.
1 - 亚油酰溶血磷脂酰胆碱氢过氧化物是从牛红细胞中纯化得到以及未从大鼠肝脏中纯化得到的谷胱甘肽过氧化物酶（GPx）的底物。牛红细胞GPx与1 - 亚油酰溶血磷脂酰胆碱氢过氧化物的初始反应速率分别约为过氧化氢和亚油酸氢过氧化物反应速率的76%和95%。对于大鼠肝脏GPx，这些初始反应速率分别约为66%和75%。计算得出，牛红细胞和大鼠肝脏中的GPx与1 - 亚油酰溶血磷脂酰胆碱氢过氧化物反应的速率常数分别约为3×10⁷M⁻¹s⁻¹和约2×10⁶M⁻¹s⁻¹。通过使用脂质过氧化的动力学模型，我们通过模拟发现：（1）体内溶血磷脂氢过氧化物的主要来源是线粒体内膜和内质网中溶血磷脂的过氧化；（2）一种能够直接还原溶血磷脂氢过氧化物的特殊酶对于这些氢过氧化物的还原很重要，因为由酰基酯键裂解酶作用介导的这些物质的解毒效率不高；（3）在线粒体内膜和内质网的胞质相中，通过GPx的还原作用比磷脂氢过氧化物谷胱甘肽过氧化物酶（PHGPx）占主导；（4）在内质网的腔相中，PHGPx占主导。
