Studies on the Enzyme Reaction Mechanism of Cytochrome P450

细胞色素P450及其电子传递系统在生物大分子和外源生物的代谢中起着重要的作用。P450酶通过在底物中引入一个氧原子来催化各种底物的氧化。我们在氧化体系方面的研究工作如下：(1)黄素与亚铁血红素之间的电子转移机理一直是人们关注的焦点。因此，人们制备了分子内连接的黄素-卟啉络合物来阐明黄素-血红素的电子转移及其瞬变性质。此外，还合成了N-苄基-1，4-二氢烟酰胺类化合物作为NAD(P)H辅酶的模型。然后，根据紫外光谱和氧化还原电势数据讨论了空间和电子效应。(2)研究了P450酶模型体系，揭示了P450的酶机理。此外，还制备了多肽结合的Fe(III)TPPCl，以考虑P450中氯化血红素周围蛋白质的环境效应。(3)在细胞色素P450的单加氧反应中，金属卟啉氧烯络合物被认为是底物氧化的最终活性物种。在本研究中，提出了酰基过氧基金属卟啉生成金属卟啉杂环化合物的机理。

Cytochrome P450 and its electron transfer system play an important role in metabolizing biomolecules and xenobiotics. The P450 enzyme catalyzes the oxidation of various substrates by the introduction of one oxygen atom into a substrate from dioxygen. Our research projects concerning the oxidation system are shown below.(1) Much interests have been focused on the mechanism of the electron transfer between the flavin and the heme. Hence, intramolecular linked flavin- porphyrin complexes have been prepared to elucidate the flavin-heme electron transfer and its transient nature. Furthermore, N-benzyl-1,4- dihydronicotinamide compounds have been synthesized as the model of NAD(P)H coenzyme. Then, the steric and electronic effects have been discussed based on UV spectra and redox potential data.(2) P450 enzyme model systems have been studied to reveal the enzyme mechanism of P450. Furthermore, polypeptide-bound Fe(III)TPPCl has been prepared to consider environmental effects of protein around hemin in P450.(3) In cytochrome P450 monooxygenations, metalloporphyrin oxenoid complex is considered to be an ultimate reactive species which is responsible for the oxidation of substrates. In the research, the formation mechanism of the metalloporphyrin oxenoid via acylperoxy metalloporphyrin was proposed.