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Reactions of N-Nitroso Compounds with Heme

N-亚硝基化合物与血红素的反应

基本信息

批准号：
7336232
负责人：
George Bannerman Richter-Addo
金额：
$ 8.33万
依托单位：
UNIVERSITY OF OKLAHOMA
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2007-05-02
项目状态：
已结题

项目摘要

Nitric oxide (NO) is now one of the most studied small molecules in bioinorganic chemistry, and new discoveries of the consequence of NO binding to the metal center in heme continue to be made. N -nitroso compounds are also very important in the field of nitric oxide chemistry. Not only can they serve as sources of NOfor metal-NO bond formation, but they are also associated with incidences of cancer after biochemical activation of nitrosamines and related compounds by the heme-containing cytochrome P450 enzyme. The iron center in cytochrome P450 has been implicated in some metabolic reactions of N -nitroso compounds. Surprisingly, however, metalloporphyrin-nitrosamine chemistry is an unexplored area of research. The biological and environmental occurrence of N -nitroso compounds, and the fact that they are metabolized by the heme-containing cytochrome P450 enzymes, underscores the necessity to examine their (N -nitroso) interactions with heme models and with heme-containing proteins as a means of better understanding their fundamental chemistry. In this proposal, we hypothesize that the bio-related chemistry of various organic N -nitroso compounds is interwoven with the chemistry of NO, and that heme iron is an important contributor in the biological NO-to-XNO conversion. Thus, a detailed knowledge of iron porphyrin-nitrosamine chemistry and subsequent Fe-NO bond formation will provide the necessary information needed to help elucidate some of the important metabolic pathways that involve nitrosamine interactions with heme biomolecules such as cytochrome P450. We have previously reported the preparation and reactions of a number of nitrosyl and nitroso (nitrosamine, nitrosoarene, nitrosothiol, etc.) complexes of metalloporphyrins. We are now entering the second major phase of our study to develop the representative reaction chemistry of these nitrosyl and nitroso metalloporphyrins. We propose to examine the interactions of nitrosamines and related compounds with heme models and with cytochrome P450 BM3 (both the heme domain and the full-length protein), and elucidate the reaction pathways of these heme-nitrosamine complexes. This planned research is fundamental to the understanding of the heme-dependent bioinorganic chemistry of NO. !__

一氧化氮（NO）是目前生物无机化学中研究最多的小分子之一，也是新发现的

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Crystallographic trapping of heme loss intermediates during the nitrite-induced degradation of human hemoglobin.

DOI：
10.1021/bi2009322
发表时间：
2011-10-04
期刊：
BIOCHEMISTRY
影响因子：
2.9
作者：
Yi, Jun;Thomas, Leonard M.;Musayev, Faik N.;Safo, Martin K.;Richter-Addo, George B.
通讯作者：
Richter-Addo, George B.

Fiber-optic infrared spectroelectrochemical studies of six-coordinate manganese nitrosyl porphyrins in nonaqueous media.

非水介质中六配位亚硝酰锰卟啉的光纤红外光谱电化学研究。