Wink D A, Mitchell J B
Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Free Radic Biol Med. 1998 Sep;25(4-5):434-56. doi: 10.1016/s0891-5849(98)00092-6.
There has been confusion as to what role(s) nitric oxide (NO) has in different physiological and pathophysiological mechanisms. Some studies imply that NO has cytotoxic properties and is the genesis of numerous diseases and degenerative states, whereas other reports suggest that NO prevents injurious conditions from developing and promotes events which return tissue to homeostasis. The primary determinant(s) of how NO affects biological systems centers on its chemistry. The chemistry of NO in biological systems is extensive and complex. To simplify this discussion, we have formulated the "chemical biology of NO" to describe the pertinent chemical reactions under specific biological conditions. The chemical biology of NO is divided into two major categories, direct and indirect. Direct effects are defined as those reactions fast enough to occur between NO and specific biological molecules. Indirect effects do not involve NO, but rather are mediated by reactive nitrogen oxide species (RNOS) formed from the reaction of NO either with oxygen or superoxide. RNOS formed from NO can mediate either nitrosative or oxidative stress. This report discusses various aspects of the chemical biology of NO relating to biological molecules such as guanylate cyclase, cytochrome P450, nitric oxide synthase, catalase, and DNA and explores the potential roles of NO in different biological events. Also, the implications of different chemical reactions of NO with cellular processes such as mitochondrial respiration, metal homeostasis, and lipid metabolism are discussed. Finally, a discussion of the chemical biology of NO in different cytotoxic mechanisms is presented.
关于一氧化氮（NO）在不同生理和病理生理机制中所起的作用一直存在混淆。一些研究表明，NO具有细胞毒性，是众多疾病和退行性状态的根源，而其他报告则表明，NO可防止有害状况的发展，并促进组织恢复稳态的过程。NO影响生物系统的主要决定因素集中在其化学性质上。生物系统中NO的化学性质广泛且复杂。为简化此讨论，我们制定了“NO的化学生物学”来描述特定生物条件下的相关化学反应。NO的化学生物学分为两大类，直接作用和间接作用。直接作用定义为NO与特定生物分子之间快速发生的那些反应。间接作用不涉及NO，而是由NO与氧气或超氧化物反应形成的活性氮氧化物（RNOS）介导。由NO形成的RNOS可介导亚硝化或氧化应激。本报告讨论了NO的化学生物学与诸如鸟苷酸环化酶、细胞色素P450、一氧化氮合酶、过氧化氢酶和DNA等生物分子相关的各个方面，并探讨了NO在不同生物事件中的潜在作用。此外，还讨论了NO与细胞过程如线粒体呼吸、金属稳态和脂质代谢的不同化学反应的影响。最后，介绍了NO在不同细胞毒性机制中的化学生物学讨论。
