抗坏血酸介导亚硝酸盐非酶还原为一氧化氮

IF 2.7
Juan Du , Milos R. Filipović , Brett A. Wagner , Garry R. Buettner
{"title":"抗坏血酸介导亚硝酸盐非酶还原为一氧化氮","authors":"Juan Du ,&nbsp;Milos R. Filipović ,&nbsp;Brett A. Wagner ,&nbsp;Garry R. Buettner","doi":"10.1016/j.arres.2023.100079","DOIUrl":null,"url":null,"abstract":"<div><p>Nitric oxide (NO<sup>•</sup>) generated by nitric oxide synthases is involved in many physiological and pathophysiological processes. However, non-enzymatic formation of NO<sup>•</sup> also occurs <em>in vivo</em>. Here we investigated the production of NO<sup>•</sup> from nitrite, as facilitated by ascorbate, over the pH range of 2.4–7.4. Using a nitric oxide electrode, we observed at low pH a rapid generation of NO<sup>•</sup> from nitrite and ascorbate that slows with increasing pH. The formation of NO<sup>•</sup> was confirmed by its reaction with oxyhemoglobin. In the ascorbate/nitrite system a steady-state level of NO<sup>•</sup> was achieved, suggesting that a futile redox cycle of nitrite-reduction by ascorbate and NO<sup>•</sup>-oxidation by dioxygen was established. However, at pH-values of around 7 and greater, the direct reduction of nitrite by ascorbate is very slow; thus, this route to the non-enzymatic production of NO<sup>•</sup> is not likely to be significant process <em>in vivo</em> in environments having a pH around 7.4. The production of nitric oxide by nitrite and ascorbate would be important only in areas of lower pH, <em>e.g.</em> stomach/digestive system, sites of inflammation, and areas of hypoxia such as tumor tissue. In patients receiving very large doses of ascorbate delivered by intravenous infusion, plasma levels of ascorbate on the order of 20 - 30 mM can be achieved. After infusion, levels of nitrate and nitrite in plasma were unchanged. Thus, in blood and tissue that maintain a pH of about 7.4, the reduction of nitrite to nitric oxide by ascorbate appears to be insignificant, even at very large, pharmacological levels of ascorbate.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100079"},"PeriodicalIF":2.7000,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486277/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide\",\"authors\":\"Juan Du ,&nbsp;Milos R. Filipović ,&nbsp;Brett A. Wagner ,&nbsp;Garry R. Buettner\",\"doi\":\"10.1016/j.arres.2023.100079\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Nitric oxide (NO<sup>•</sup>) generated by nitric oxide synthases is involved in many physiological and pathophysiological processes. However, non-enzymatic formation of NO<sup>•</sup> also occurs <em>in vivo</em>. Here we investigated the production of NO<sup>•</sup> from nitrite, as facilitated by ascorbate, over the pH range of 2.4–7.4. Using a nitric oxide electrode, we observed at low pH a rapid generation of NO<sup>•</sup> from nitrite and ascorbate that slows with increasing pH. The formation of NO<sup>•</sup> was confirmed by its reaction with oxyhemoglobin. In the ascorbate/nitrite system a steady-state level of NO<sup>•</sup> was achieved, suggesting that a futile redox cycle of nitrite-reduction by ascorbate and NO<sup>•</sup>-oxidation by dioxygen was established. However, at pH-values of around 7 and greater, the direct reduction of nitrite by ascorbate is very slow; thus, this route to the non-enzymatic production of NO<sup>•</sup> is not likely to be significant process <em>in vivo</em> in environments having a pH around 7.4. The production of nitric oxide by nitrite and ascorbate would be important only in areas of lower pH, <em>e.g.</em> stomach/digestive system, sites of inflammation, and areas of hypoxia such as tumor tissue. In patients receiving very large doses of ascorbate delivered by intravenous infusion, plasma levels of ascorbate on the order of 20 - 30 mM can be achieved. After infusion, levels of nitrate and nitrite in plasma were unchanged. Thus, in blood and tissue that maintain a pH of about 7.4, the reduction of nitrite to nitric oxide by ascorbate appears to be insignificant, even at very large, pharmacological levels of ascorbate.</p></div>\",\"PeriodicalId\":72106,\"journal\":{\"name\":\"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe\",\"volume\":\"9 \",\"pages\":\"Article 100079\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486277/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S266713792300019X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266713792300019X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

一氧化氮合酶产生的一氧化氮(NO•)参与了许多生理和病理生理过程。然而,NO•的非酶促形成也发生在体内。在这里,我们研究了在2.4–7.4的pH范围内,在抗坏血酸的促进下,亚硝酸盐产生NO•。使用一氧化氮电极,我们观察到在低pH下,亚硝酸盐和抗坏血酸快速生成NO•,随着pH的增加,生成速度减慢。NO•的形成通过其与氧合血红蛋白的反应得到证实。在抗坏血酸盐/亚硝酸盐体系中,NO•达到了稳态水平,这表明抗坏血酸盐还原亚硝酸盐和双氧氧化NO•的氧化还原循环是徒劳的。然而,在约7及更大的pH值下,抗坏血酸盐对亚硝酸盐的直接还原非常缓慢;因此,在pH约7.4的环境中,这种非酶促产生NO•的途径在体内不太可能是一个重要的过程。只有在pH较低的区域,如胃/消化系统、炎症部位和缺氧区域(如肿瘤组织),亚硝酸盐和抗坏血酸产生一氧化氮才是重要的。在接受静脉输注的大剂量抗坏血酸的患者中,可以达到20-30 mM的抗坏血酸血浆水平。输注后,血浆中的硝酸盐和亚硝酸盐水平没有变化。因此,在维持约7.4的pH的血液和组织中,抗坏血酸盐将亚硝酸盐还原为一氧化氮似乎是微不足道的,即使在非常大的抗坏血酸药理学水平下也是如此。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide

Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide

Nitric oxide (NO) generated by nitric oxide synthases is involved in many physiological and pathophysiological processes. However, non-enzymatic formation of NO also occurs in vivo. Here we investigated the production of NO from nitrite, as facilitated by ascorbate, over the pH range of 2.4–7.4. Using a nitric oxide electrode, we observed at low pH a rapid generation of NO from nitrite and ascorbate that slows with increasing pH. The formation of NO was confirmed by its reaction with oxyhemoglobin. In the ascorbate/nitrite system a steady-state level of NO was achieved, suggesting that a futile redox cycle of nitrite-reduction by ascorbate and NO-oxidation by dioxygen was established. However, at pH-values of around 7 and greater, the direct reduction of nitrite by ascorbate is very slow; thus, this route to the non-enzymatic production of NO is not likely to be significant process in vivo in environments having a pH around 7.4. The production of nitric oxide by nitrite and ascorbate would be important only in areas of lower pH, e.g. stomach/digestive system, sites of inflammation, and areas of hypoxia such as tumor tissue. In patients receiving very large doses of ascorbate delivered by intravenous infusion, plasma levels of ascorbate on the order of 20 - 30 mM can be achieved. After infusion, levels of nitrate and nitrite in plasma were unchanged. Thus, in blood and tissue that maintain a pH of about 7.4, the reduction of nitrite to nitric oxide by ascorbate appears to be insignificant, even at very large, pharmacological levels of ascorbate.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
2.60
自引率
0.00%
发文量
0
审稿时长
46 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信