The chemistry of the S -nitrosoglutathione/glutathione system
Open accessAbstract
S-Nitrosothiols have generated considerable interest due to their ability to act as nitric oxide (NO) donors and due to their possible involvement in bioregulatory systems-e.g., NO transfer reactions. Elucidation of the reaction pathways involved in the modification of the thiol group by S-nitrosothiols is important for understanding the role of S-nitroso compounds in vivo. The modification of glutathione (GSH) in the presence of S-nitrosoglutathione (GSNO) was examined as a model reaction. Incubation of GSNO (1 mM) with GSH at various concentrations (1-10 mM) in phosphate buffer (pH 7.4) yielded oxidized glutathione, nitrite, nitrous oxide, and ammonia as end products. The product yields were dependent on the concentrations of GSH and oxygen. Transient signals corresponding to GSH conjugates, which increased by one mass unit when the reaction was carried out with 15N-labeled GSNO, were identified by electrospray ionization mass spectrometry. When morpholine was present in the reaction system, N-nitrosomorpholine was formed. Increasing concentrations of either phosphate or GSH led to lower yields of N-nitrosomorpholine. The inhibitory effect of phosphate may be due to reaction with the nitrosating agent, nitrous anhydride (N2O3), formed by oxidation of NO. This supports the release of NO during the reaction of GSNO with GSH. The products noted above account quantitatively for virtually all of the GSNO nitrogen consumed during the reaction, and it is now possible to construct a complete set of pathways for the complex transformations arising from GSNO + GSH.
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Taken together, nitrite reacts with S8 and, seemingly less efficiently, with polysulfides in non-aqueous polar solvents to form products including SSNO-.
“Taken together, nitrite reacts with S8 and, seemingly less efficiently, with polysulfides in non-aqueous polar solvents leading to the formation of similar products as observed previously in the reaction of NO with sulfide [69], and nitrosothiols with thiols [70], and with sulfide [19,71] including SSNO -.”
From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [70]
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- Authors
- Singh, S. P., Wishnok, J. S., Keshive, M., Deen, W. M., & Tannenbaum, S. R.
- Affiliations
- Massachusetts Institute of Technology (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-12-10
- Volume
- 93
- Issue
- 25
- Pages
- 14428-14433
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC26149
- OpenAlex
- W2080031356
- Cited by
- 336
- References
- 37
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 14 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 15 · 2017: 12 · 2016: 7 · 2015: 9 · 2014: 12 · 2013: 10 · 2012: 16
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA-26731, P01CA026731)
- National Institute of Environmental Health Sciences (ES07020, T32ES007020)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- S-nitrosoglutathione, glutathione, S-nitrosothiols, nitric oxide donors, thiol modification, nitrosation, N-nitrosomorpholine, reaction pathways, bioregulation
- MeSH terms
- Glutathione, Models, Chemical, Nitroso Compounds, Oxidation-Reduction, S-Nitrosoglutathione
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