Mechanism of Nitric Oxide Release from S-Nitrosothiols
Open accessAbstract
S-Nitrosothiols have many biological activities and have been suggested to be intermediates in signal transduction. The mechanism and products of S-nitrosothiol decomposition are of great significance to the understanding of nitric oxide (.NO) biochemistry. S-Nitrosothiols are stable compounds at 37 degrees C and pH 7.4 in the presence of transition metal ion chelators. The presence of trace transition metal ions (present in all buffers) stimulates the catalytic breakdown of S-nitrosothiols to .NO and disulfide. Thiyl radicals are not formed as intermediates in this process. Photolysis of S-nitrosothiols results in the formation of .NO and disulfide via the intermediacy of thiyl radicals. Reduced metal ion (e.g. Cu+) decomposes S-nitrosothiols more rapidly than oxidized metal ion (e.g. Cu2+) indicating that reducing agents such as glutathione and ascorbate can stimulate decomposition of S-nitrosothiol by chemical reduction of contaminating transition metal ions. Transnitrosation can also stimulate S-nitrosothiol decomposition if the product S-nitrosothiol is more susceptible to transition metal ion-catalyzed decomposition than the parent S-nitrosothiol. Equilibrium constants for the transnitrosation reactions of reduced glutathione, either with S-nitroso-N-acetyl-dl-penicillamine or with S-nitroso-L-cysteine indicate that S-nitrosoglutathione formation is favored. The biological relevance of S-nitrosothiol decomposition is discussed.
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RSNOs can release NO via thermal or photo-initiated homolytic cleavage of the S-N bond, forming thiyl and NO radicals, with thiyl radical reacting with another RSNO to form disulfide and another NO radical.
“Thermal or photo-initiated decomposition will lead to homolytic cleavage of the S-N bond, and form thiyl and NO radicals, where thiyl radical (RS•) will react with another RSNO and generate disulfide (RSSR) and another NO radical.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [167]
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- Authors
- Singh, R. J., Hogg, N., Joseph, J., & Kalyanaraman, B.
- Affiliations
- Medical College of Wisconsin (US)
- Corresponding author
- Kalyanaraman, B.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 271
- Issue
- 31
- Pages
- 18596-18603
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2011582460
- Cited by
- 600
- References
- 5
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 15 · 2023: 20 · 2022: 24 · 2021: 16 · 2020: 12 · 2019: 26 · 2018: 25 · 2017: 19 · 2016: 22 · 2015: 16 · 2014: 18 · 2013: 23 · 2012: 21
- FWCI
- 14.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29hl045058-03, 5p01ca049089-06)
- National Heart, Lung, and Blood Institute (HL45058)
- National Cancer Institute (CA 49089)
- National Center for Research Resources (P41RR001008, RR 01008)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- S-nitrosothiols, nitric oxide release, transition metal catalysis, thiyl radicals, photolysis, transnitrosation, S-nitrosoglutathione, S-nitroso-N-acetylpenicillamine, S-nitroso-L-cysteine, glutathione, vitamin C, disulfide bond formation, signal transduction
- MeSH terms
- Cyclic N-Oxides, Electron Spin Resonance Spectroscopy, Free Radicals, Glutathione, Kinetics, Mercaptoethanol, Nitric Oxide, Nitroso Compounds, Penicillamine, Photolysis, Spin Labels, Sulfhydryl Compounds, Molecular Structure, Glutathione Disulfide, S-Nitrosothiols, S-Nitrosoglutathione, S-Nitroso-N-Acetylpenicillamine
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