LIPID OXIDATION IN BIOLOGICAL-MEMBRANES - ELECTRON-TRANSFER PROTEINS AS INITIATORS OF LIPID AUTOXIDATION
LIPID OXIDATION IN BIOLOGICAL-MEMBRANES - ELECTRON-TRANSFER PROTEINS AS INITIATORS OF LIPID AUTOXIDATION
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DOI：
10.1016/0003-9861(75)90036-3
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发表时间：
1975-01-01
影响因子：
3.9
通讯作者：
HATEFI, Y
中科院分区：
文献类型：
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作者：
KASCHNITZ, RM;HATEFI, Y
以磷脂为底物，细胞膜中的电子传递蛋白为催化剂，在模型体系中研究了生物脂质的自氧化反应。血红素化合物，黄素蛋白，铁硫蛋白的能力，启动脂质自氧化进行了检查。在所测试的许多血红素化合物中，活性最高的是血红素、微过氧化物酶、高铁血红蛋白、细胞色素。与新鲜的磷脂制剂，反应速率（纳摩尔的氧气/分钟的血红素纳摩尔）范围从5（细胞色素）到350（血红素）。只有氧化的血红素化合物作为催化剂是活性的。还原血红素化合物、黄素蛋白和核黄素无活性。在血红素化合物的存在下，老化的超声处理的磷脂制剂比新鲜的制剂更迅速地氧化。从它们在234 nm处的特征二烯吸收峰判断，它们还具有较高含量的脂肪酸氢过氧化物。这一观察结果与假定的血红素化合物的脂质自氧化机制一致，即预先形成的脂肪酸氢过氧化物的均裂断裂。铁硫蛋白在适当的铁螯合剂（邻菲咯啉或2，2 ′-联吡啶）或离液离子存在下失稳时，也可作为脂质自氧化的引发剂。氧摄取率（纳摩尔氧/分钟×毫克蛋白质）从从复合物I分离的铁硫蛋白的约200到巴氏梭菌的约5500不等。然而，每纳摩尔不稳定硫化物，所有活性铁硫蛋白的速率为4-7 nmol氧/min × nmol不稳定硫化物。超氧化物生成系统不启动脂质自氧化，赤铜蛋白也不抑制血红素化合物或铁氧还蛋白诱导的自氧化。然而，由其他两个铁硫蛋白诱导的脂质氧化被赤铜蛋白部分抑制。结果表明，在上述体系中，超氧阴离子既不是脂质自氧化的引发剂，也不是脂质自氧化的必然中间体。
Biological lipid autoxidation has been studied in a model system composed of sonicated phospholipids as substrate and electron transfer proteins found in membranes as possible catalysts. Heme compounds, flavoproteins, and iron-sulfur proteins were examined for their ability to initiate lipid autoxidation. Among many heme compounds tested, the most active were hematin ⩾microperoxidase ⪢ methemoglobin > cytochromec. With fresh preparations of phospholipids, reaction rates (nanomoles of oxygen/minute nanomoles of heme) ranged from 5 (cytochromec) to 350 (hematin). Only the oxidized heme compounds were active as catalysts. Reduced heme compounds, flavoproteins and riboflavin were inactive. In the presence of heme compounds, aged preparations of sonicated phospholipids were much more rapidly oxidized than fresh preparations. They also had a higher content of fatty acid hydroperoxides as judged from their characteristic diene absorption peak at 234 nm. This observation agrees with the postulated mechanism of lipid autoxidation by heme compounds, namely, homolytic scission of preformed fatty acid hydroperoxides. Iron-sulfur proteins were also active as initiators of lipid autoxidation when destabilized in the presence of an appropriate iron chelator (o-phenanthroline or 2,2′-bipyridine) or a chaotropic ion. Oxygen uptake rates (nanomoles of oxygen/minute × milligrams of protein) varied from about 200 for an iron-sulfur protein isolated from complex I to about 5500 forClostridium pasteurianumferredoxin. However, per nanomole of labile sulfide, the rates for all active iron-sulfur proteins were 4–7 nmol of oxygen/min × nmol of labile sulfide.Superoxide-generating systems did not initiate lipid autoxidation, nor did erythrocuprein inhibit the autoxidations induced by heme compounds or ferredoxin. However, lipid oxidations induced by two other iron-sulfur proteins were partially inhibited by erythrocuprein. It is concluded that in the above system Superoxide anion is neither an initiator nor an obligatory intermediate of lipid autoxidation.