MOLECULAR PROBES OF MECHANISM OF CYTOCHROME P-450

已知肺、肝和上皮组织的细胞色素P-450 在致癌物激活、药物和外源生物中发挥核心作用 解毒、类固醇和前列腺素代谢。玻璃杯里的这个 程序已经阐明了有机化学和无机化学的 细胞色素P-450介导的过程统称为氧 激活和底物氧化。我们的双管齐下的方法是 (I)使用细胞色素P-450的底物，旨在揭示其性质 看不见的中间体和(Ii)开发模型系统作为化学物质 这些过程的范例。这些研究的一个重要方面是 直接比较了酶反应和模型反应中的相同 实验室。在接下来的提案中，描述了 坚持以下具体目标： (1)继续高度氧化的制备和表征 铁卟啉中间体。(2)发展低温 直接测量氧化还原电位的电化学技术 氧化铁的卟啉。(3)研究0-0键的成键机理 铁卟啉介导的卵裂。(4)继续研究 氧化铁卟啉氧化底物的机理。(5)至 理解伴随着史无前例的氢-氚交换 细胞色素P-450Lm催化丙烯环氧化(6)探索 细胞色素P-450scc的乙二醇裂解反应及乙醇氧化 细胞色素P-450LM3。(7)研究我们已发现的 芒果-辣根过氧化物酶。(8)拓展细胞色素化学 P-450有助于对生物学中的氧代谢有一个全面的了解。

The cytochromes P-450 of lung, liver and epithelial tissue are known to play a central role in carcinogen activation, drug and xenobiotic detoxification and steroid and prostaglandin metabolism. The glass of this program have been to elucidate the organic and inorganic chemistry of the processes mediated by cytochrome P-450 referred to collectively as oxygen activation and substrate oxygenation. Our two-pronged approach has been (i) to employ substrates for cytochrome P-450 designed to reveal the nature of unseen intermediates and (ii) to develop model systems as chemical paradigms for these processes. An important aspect of these studies has been the direct comparison of enzymic and model reactions in the same laboratory. In the proposal that follows experiments are described which bear on the following specific goals: (1) To continue the preparation and characterization of highly oxidized iron porphyrin intermediates. (2) To develop low temperature electrochemical techniques for the direct measurement of redox potentials of oxidized iron porphyrins. (3) To study the mechanisms of 0-0 bond cleavage mediated by iron porphyrins. (4) To continue our study of the mechanisms of substrate oxygenation by oxidized iron porphyrins. (5) To understand the unprecedented hydrogen-deuterium exchange that accompanies the epoxidation of propylene by cytochrome P-450LM. (6) To explore the glycol cleavage reaction cytochrome P-450scc and the ethanol oxidation of cytochrome P-450LM3. (7) To study the oxidase activity we have found for mangano-horseradish peroxidase. (8) To extend the chemistry of cytochrome P-450 toward a general understanding of oxygen metabolism in biology.