BIOCHEMISTRY AND HEPATIC TOXICITY OF CARBON RADICALS

碳自由基的生物化学仍然知之甚少，尽管它 与氧自由基病理的直接关系和碳的独特价值 作为机械探头的部首。这里提出的工作建立在关键的基础上 在支助期满期间垫付的款项，特别是(A) 证实了一个事实，即自由基几乎总是 由过氧化物酶产生，但仅在特定条件下由 单加氧酶，(B)催化活性的成功表达 杆状病毒系统中的辣根过氧化物酶，以及(C)发展 新型自由基探针。第一个目标是继续阐明 过氧化物酶的功能，初步强调其结构特征 它决定了蛋白质中未配对电子的位置 自由基的产生机制及可能的催化作用 单加氧酶反应。第二个目标是扩大我们不断增长的 植物和真菌过氧化物酶的生理学认识 相关的哺乳动物酶，特别是髓过氧化物酶和甲状腺 过氧化物酶。第三个目标是构建新的激进探针，并 利用它们来描述生物自由基的特征。第四个目标是 探索碳自由基的生物命运，特别是它们的 氧化成阳离子并与蛋白质发生反应。的集体意向 这些研究是为了增进我们对碳的生物化学的理解。 自由基，特别是它们形成和形成的机制 熄灭，并澄清它们的毒理潜力。

The biochemistry of carbon radicals remains poorly understood despite its direct relevance to oxygen radical pathology and the unique value of carbon radicals as mechanistic probes. The work proposed here builds on key advances made during the expiring period of support, particularly (a) validation of a rationale for the fact that radicals are almost invariably produced by peroxidases but only under certain conditions by monooxygenases, (b) successful expression of catalytically active horseradish peroxidase in a baculovirus system, and (c) development of novel free radical probes. The first goal is to continue to elucidate the function of peroxidases, with initial emphasis on the structural features that determine the location of unpaired electrons in the protein, the mechanism of free radical generation, and the possible catalysis of monooxygenase reactions. The second goal is to extend our growing understanding of plant and fungal peroxidases to the physiologically relevant mammalian enzymes, particularly myeloperoxidase and thyroid peroxidase. The third goal is to construct new radical probes and to employ them to characterize biological radicals. The fourth goal is to explore the biological fates of carbon radicals, particularly their oxidation to cations and reactions with proteins. The collective intent of these studies is to advance our understanding of the biochemistry of carbon radicals, particularly the mechanisms by which they are formed and quenched, and to clarify their toxicological potential.