REDOX REACTIVITY OF HEMOGLOBINS--SEARCH FOR A SAFER BLOOD SUBSTITUTE

许多生化反应会产生氧自由基，现在 被认可参与制定或推广多项 病理情况。因为它具有生成或交互的能力 有氧自由基，无细胞的血红蛋白可以被认为是一种有毒的 实质性的。血红蛋白的自氧化是一个重要的问题。 在使用化学修饰的血红蛋白作为携氧血液时 替身。一些修饰和未修饰的人的氧化和 通过超氧化物和过氧化氢产生的动物血红蛋白已被广泛应用 学习。这是我们持续寻找动物或突变体的一部分 表现出良好的氧化还原反应的血红蛋白，我们 希望能够更好地理解血红素之间的关系 口袋化学与血红蛋白产生或相互作用的能力 氧自由基。我们已经获得了候选人的无细胞数据 血红蛋白血液替代品表明他们的氧化速度，他们的 活性氧物种及其细胞色素P450样蛋白的产生 活性函数不是由它们的氧亲和力决定的，因此 氧化和携氧功能可独立选择 参数。在这方面，血红蛋白的潜在氧化毒性 很可能是由它的血红素口袋的立体化学决定的。结果 到目前为止，从这项工作中发现的信息已经出版，还 在国家和国际会议上介绍。

Many biochemical reactions generate oxygen free radicals that are now recognized to participate in the development or promotion of a number of pathological conditions. Because of its ability to generate or interact with oxygen free radicals, cell-free hemoglobin may be regarded as a toxic substance. Spontaneous autoxidation of hemoglobin is an important concern in the use of chemically modified hemoglobin as an oxygen-carrying blood substitute. Oxidation of a number of modified and unmodified human and animal hemoglobins by superoxide and peroxide have been extensively studied. This is part of our continuous search for animal or mutant hemoglobins that exhibit favorable oxidation- reduction reactions, which we hope will enable a better understanding of the relationship between heme pocket chemistry and the ability of hemoglobin to generate or interact with oxygen free radicals. We have obtained data on candidate cell-free hemoglobin blood substitutes that show that their rates of oxidation, their generation of activated oxygen species and their cytochrome p450-like activity functions are not determined by their oxygen affinities, so that oxidative and oxygen carrying functions are independently selectable parameters. In this regard, the potential oxidative toxicity of hemoglobin may well be determined by the stereochemistry of its heme pocket. Results transpired so far from this work have been published and were also presented at national and international meetings.