MOLECULAR PROBES OF MECHANISM OF CYTOCHROME P-450

已知肺、肝和上皮组织的细胞色素P-450 在致癌物活化、药物和异生物质中发挥核心作用 解毒以及类固醇和前列腺素代谢。 这个杯子 该计划已阐明有机和无机化学的 由细胞色素P-450介导的过程统称为氧 活化和底物氧化。 我们双管齐下的方法 (i)利用细胞色素P-450的底物， 看不见的中间体和（ii）开发模型系统作为化学 这些过程的范例。 这些研究的一个重要方面是 直接比较酶和模型反应， 实验室 在下面的建议中，描述了实验， 与下列具体目标有关： (1)为了继续制备和表征高度氧化的 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 铁卟啉的氧化物。 (3)研究0-0键的作用机理 由铁卟啉介导的裂解。 (4)为了继续研究 氧化铁卟啉的底物氧化机制。 (5)到 了解前所未有的氢氘交换， 细胞色素P-450 LM催化丙烯环氧化反应。 (6)探讨 乙二醇裂解反应细胞色素P-450 SCC和乙醇氧化 细胞色素P-450 LM 3。 (7)为了研究我们发现的氧化酶活性， 锰辣根过氧化物酶 (8)为了扩展细胞色素的化学性质 P-450对生物学中氧代谢的一般理解。

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.