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....
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
|
| Series: | Advances in Redox Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266713792300019X |
| _version_ | 1797398428862382080 |
|---|---|
| author | Juan Du Milos R. Filipović Brett A. Wagner Garry R. Buettner |
| author_facet | Juan Du Milos R. Filipović Brett A. Wagner Garry R. Buettner |
| author_sort | Juan Du |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:25:26Z |
| format | Article |
| id | doaj.art-7c7bece3bd724fa389e1838f0d403ead |
| institution | Directory Open Access Journal |
| issn | 2667-1379 |
| language | English |
| last_indexed | 2024-03-09T01:25:26Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Redox Research |
| spelling | doaj.art-7c7bece3bd724fa389e1838f0d403ead2023-12-10T06:18:51ZengElsevierAdvances in Redox Research2667-13792023-12-019100079Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxideJuan Du0Milos R. Filipović1Brett A. Wagner2Garry R. Buettner3Free Radical and Radiation Biology & ESR Facility, The University of Iowa, Med Labs B-180, Iowa City, IA, United StatesLeibniz Institute for Analytical Sciences, ISAS e.V. Dortmund, GermanyFree Radical and Radiation Biology & ESR Facility, The University of Iowa, Med Labs B-180, Iowa City, IA, United StatesFree Radical and Radiation Biology & ESR Facility, The University of Iowa, Med Labs B-180, Iowa City, IA, United States; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S266713792300019XAscorbateNitric oxideand Nitrite |
| spellingShingle | Juan Du Milos R. Filipović Brett A. Wagner Garry R. Buettner Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide Advances in Redox Research Ascorbate Nitric oxide and Nitrite |
| title | Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide |
| title_full | Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide |
| title_fullStr | Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide |
| title_full_unstemmed | Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide |
| title_short | Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide |
| title_sort | ascorbate mediates the non enzymatic reduction of nitrite to nitric oxide |
| topic | Ascorbate Nitric oxide and Nitrite |
| url | http://www.sciencedirect.com/science/article/pii/S266713792300019X |
| work_keys_str_mv | AT juandu ascorbatemediatesthenonenzymaticreductionofnitritetonitricoxide AT milosrfilipovic ascorbatemediatesthenonenzymaticreductionofnitritetonitricoxide AT brettawagner ascorbatemediatesthenonenzymaticreductionofnitritetonitricoxide AT garryrbuettner ascorbatemediatesthenonenzymaticreductionofnitritetonitricoxide |