Chevion M
Department of Cellular Biochemistry, Hebrew University of Jerusalem, Israel.
Free Radic Biol Med. 1988;5(1):27-37. doi: 10.1016/0891-5849(88)90059-7.
The metal-mediated site-specific mechanism for free radical-induced biological damage is reviewed. According to this mechanism, cooper- or iron-binding sites on macromolecules serve as centers for repeated production of hydroxyl radicals that are generated via the Fenton reaction. The aberrations induced by superoxide, ascorbate, isouramil, and paraquat are summarized. An illustrative example is the enhancement of double-strand breaks by ascorbate/copper. Prevention of the site-specific free radical damage can be accomplished by using selective chelators for iron and copper, by displacing these redox-active metals with other redox-inactive metals such as zinc, by introducing high concentrations of hydroxyl radicals scavengers and spin trapping agents, and by applying protective enzymes that remove superoxide or hydrogen peroxide. Histidine is a special agent that can intervene in free radical reactions in variety of modes. In biological systems, there are traces of copper and iron that are at high enough levels to catalyze free-radical reactions, and account for such deleterious processes. In the human body Fe/Cu = 80/1 (w/w). Nevertheless, both (free) copper and iron are soluble enough, and the rate constants of their reduced forms with hydrogen peroxide are sufficiently high to suggest that they might be important mediators of free radical toxicity.
本文综述了自由基诱导生物损伤的金属介导位点特异性机制。根据这一机制，大分子上的铜或铁结合位点充当通过芬顿反应产生羟基自由基的重复生成中心。总结了超氧化物、抗坏血酸、异尿嘧啶和百草枯所诱导的畸变。一个说明性的例子是抗坏血酸/铜对双链断裂的增强作用。通过使用铁和铜的选择性螯合剂、用其他氧化还原惰性金属（如锌）取代这些氧化还原活性金属、引入高浓度的羟基自由基清除剂和自旋捕获剂以及应用去除超氧化物或过氧化氢的保护酶，可以预防位点特异性自由基损伤。组氨酸是一种可以以多种方式干预自由基反应的特殊物质。在生物系统中，存在痕量的铜和铁，其含量足以催化自由基反应，并导致此类有害过程。在人体中，铁/铜 = 80/1（重量/重量）。然而，（游离）铜和铁都具有足够的溶解性，它们的还原形式与过氧化氢的反应速率常数足够高，表明它们可能是自由基毒性的重要介质。
