Bryk R, Griffin P, Nathan C
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Nature. 2000 Sep 14;407(6801):211-5. doi: 10.1038/35025109.
Nitric oxide (NO) is present in soil and air, and is produced by bacteria, animals and plants. Superoxide (O2-) arises in all organisms inhabiting aerobic environments. Thus, many organisms are likely to encounter peroxynitrite (OONO-), a product of NO and O2- that forms at near diffusion-limited rates, and rapidly decomposes upon protonation through isomerization to nitrate (NO3-; ref. 1) while generating hydroxyl radical (*OH) and nitrogen dioxide radical (*NO2) (refs 2, 3), both more reactive than peroxynitrite's precursors. The oxidative, inflammatory, mutagenic and cytotoxic potential (ref. 4) of peroxynitrite contrasts with the antioxidant, anti-inflammatory and tissue-protective properties ascribed to NO itself. Thus, the ability of cells to cope with peroxynitrite is central in determining the biological consequences of NO production. We considered whether cells might be equipped with enzymes to detoxify peroxynitrite. Peroxiredoxins have been identified in most genomes sequenced, but their functions are only partly understood. Here we show that the peroxiredoxin alkylhydroperoxide reductase subunit C (AhpC) from Salmonella typhimurium catalytically detoxifies peroxynitrite to nitrite fast enough to forestall the oxidation of bystander molecules such as DNA. Results are similar with peroxiredoxins from Mycobacterium tuberculosis and Helicobacter pylori. Thus, peroxynitrite reductase activity may be widespread among bacterial genera.
一氧化氮（NO）存在于土壤和空气中，由细菌、动物和植物产生。超氧化物（O2-）在所有栖息于有氧环境的生物中都会产生。因此，许多生物很可能会遇到过氧亚硝酸盐（OONO-），它是NO和O2-的产物，以接近扩散限制的速率形成，并在质子化后通过异构化迅速分解为硝酸盐（NO3-；参考文献1），同时生成羟基自由基（*OH）和二氧化氮自由基（*NO2）（参考文献2、3），这两种自由基的反应性都比过氧亚硝酸盐的前体更强。过氧亚硝酸盐的氧化、炎症、诱变和细胞毒性潜力（参考文献4）与归因于NO本身的抗氧化、抗炎和组织保护特性形成对比。因此，细胞应对过氧亚硝酸盐的能力是决定NO产生的生物学后果的关键。我们考虑细胞是否可能配备了使过氧亚硝酸盐解毒的酶。在大多数已测序的基因组中都发现了过氧化物酶，但对它们的功能仅了解一部分。在这里我们表明，鼠伤寒沙门氏菌的过氧化物酶烷基过氧化氢还原酶亚基C（AhpC）能将过氧亚硝酸盐催化解毒为亚硝酸盐，速度快到足以防止旁观者分子如DNA的氧化。来自结核分枝杆菌和幽门螺杆菌的过氧化物酶也有类似结果。因此，过氧亚硝酸盐还原酶活性可能在细菌属中广泛存在。
