The Haber-Weiss reaction and mechanisms of toxicity
The Haber-Weiss reaction and mechanisms of toxicity
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DOI：
10.1016/s0300-483x(00)00231-6
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发表时间：
2000-08-14
期刊：
影响因子：
4.5
通讯作者：
Kehrer, JP
中科院分区：
文献类型：
--
作者：
Kehrer, JP
高活性羟基自由基（HO.）可能是由超氧化物（O-2（.-））而过氧化氢（H2 O2）是在哈伯教授1934年发表的最后一篇论文中（与约瑟夫韦斯）提出的。直到人们认识到自由基是在生物系统中产生的，这一发现似乎与生物学无关。然而，在发现O-2（.-）是一种正常的细胞代谢产物，人们很快就认识到Haber-Weiss反应（O-2（.-）+ H2O2 --> HO。+ O-2 + HO-）可能提供了产生更多毒性自由基的手段。虽然碱性反应在水溶液中的二级速率常数为零，因此不能在生物系统中发生，但这些作者讨论了铁盐作为催化剂的能力。由于过渡金属离子，特别是铁，在生物系统中以低水平存在，因此该途径（通常称为铁催化的Haber-Weiss反应）已被广泛假定为解释高反应性HO的体内产生。最近的数据记录氧化还原调节各种细胞信号传导途径的重要性，清楚地表明，自由基是正常的细胞功能所必需的。然而，这也表明，在许多不同水平上破坏自由基的产生或防御可能会对细胞产生不利影响。虽然一代HO.，这是迄今为止最具活性的氧物质，通常表明明显的毒性事件，正是通过这一水平的研究，我们已经更好地理解了自由基作为信号分子和毒性物质。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
The concept that the highly reactive hydroxyl radical (HO.) could be generated from an interaction between superoxide (O-2(.-)) and hydrogen peroxide (H2O2) was proposed (with Joseph Weiss) in Professor Haber's final paper published in 1934. Until it was recognized that free radicals are produced in biological systems, this finding seemed to have no relevance to biology. However, following the discovery that O-2(.-) was a normal cellular metabolite, it was quickly recognized that the Haber-Weiss reaction (O-2(.-) + H2O2 --> HO. + O-2 + HO-) might provide a means to generate more toxic radicals. Although the basic reaction has a second order rate constant of zero in aqueous solution and thus cannot occur in biological systems, the ability of iron salts to serve as catalysts was discussed by these authors. Because transition metal ions, particularly iron, are present at low levels in biological systems, this pathway (commonly referred to as the iron-catalyzed Haber-Weiss reaction) has been widely postulated to account for the in vivo generation of the highly reactive HO.. Recent data documenting the importance of redox regulation of various cellular signaling pathways makes it clear that free radicals are essential for normal cellular function. However, this also makes it obvious that disruptions of free radical production or defenses at many different levels can lead to adverse effects on cells. While the generation of HO., which is by far the most reactive oxygen species, is generally indicative of an overtly toxic event, it is through studies at this level that we have reached a better understanding of free radicals as both signaling molecules and toxic species. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.