Department of Biochemical Sciences, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
Antioxid Redox Signal. 2012 Aug 15;17(4):684-716. doi: 10.1089/ars.2011.4196. Epub 2012 Mar 16.
Nitrite, previously considered physiologically irrelevant and a simple end product of endogenous nitric oxide (NO) metabolism, is now envisaged as a reservoir of NO to be activated in response to oxygen (O(2)) depletion. In the first part of this review, we summarize and compare the mechanisms of nitrite-dependent production of NO in selected bacteria and in eukaryotes. Bacterial nitrite reductases, which are copper or heme-containing enzymes, play an important role in the adaptation of pathogens to O(2) limitation and enable microrganisms to survive in the human body. In mammals, reduction of nitrite to NO under hypoxic conditions is carried out in tissues and blood by an array of metalloproteins, including heme-containing proteins and molybdenum enzymes. In humans, tissues play a more important role in nitrite reduction, not only because most tissues produce more NO than blood, but also because deoxyhemoglobin efficiently scavenges NO in blood. In the second part of the review, we outline the significance of nitrite in human health and disease and describe the recent advances and pitfalls of nitrite-based therapy, with special attention to its application in cardiovascular disorders, inflammation, and anti-bacterial defence. It can be concluded that nitrite (as well as nitrate-rich diet for long-term applications) may hold promise as therapeutic agent in vascular dysfunction and ischemic injury, as well as an effective compound able to promote angiogenesis.
亚硝酸盐曾被认为在生理上无足轻重，只是内源性一氧化氮（NO）代谢的简单终产物，但现在被认为是一种 NO 的储备库，可以在缺氧时被激活。在这篇综述的第一部分，我们总结并比较了亚硝酸盐依赖型 NO 产生的机制，分别在选定的细菌和真核生物中进行了比较。细菌中的亚硝酸盐还原酶是含铜或血红素的酶，在病原体对氧气限制的适应中发挥着重要作用，使微生物能够在人体中存活。在哺乳动物中，在缺氧条件下，一系列金属蛋白酶，包括含血红素的蛋白和钼酶，将亚硝酸盐还原为 NO。在人体中，组织在亚硝酸盐还原中起着更重要的作用，不仅因为大多数组织产生的 NO 比血液多，而且因为脱氧血红蛋白能有效地在血液中清除 NO。在综述的第二部分，我们概述了亚硝酸盐在人类健康和疾病中的重要性，并描述了基于亚硝酸盐的治疗方法的最新进展和陷阱，特别关注其在心血管疾病、炎症和抗菌防御中的应用。可以得出结论，亚硝酸盐（以及硝酸盐丰富的饮食，适用于长期应用）可能作为治疗血管功能障碍和缺血损伤的有前途的药物，以及一种有效的促进血管生成的化合物。
