Mechanism of nitric oxide release from S-nitrosothiols

J Biol Chem. 1996 Aug 2;271(31):18596-603. doi: 10.1074/jbc.271.31.18596.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cyclic N-Oxides
  • Electron Spin Resonance Spectroscopy
  • Free Radicals / chemistry
  • Free Radicals / metabolism
  • Glutathione / analogs & derivatives
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Glutathione Disulfide
  • Kinetics
  • Mercaptoethanol*
  • Molecular Structure
  • Nitric Oxide / metabolism*
  • Nitroso Compounds / chemistry
  • Nitroso Compounds / metabolism*
  • Penicillamine / analogs & derivatives
  • Photolysis
  • S-Nitroso-N-Acetylpenicillamine
  • S-Nitrosoglutathione
  • S-Nitrosothiols*
  • Spin Labels
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / metabolism


  • Cyclic N-Oxides
  • Free Radicals
  • Nitroso Compounds
  • S-Nitrosothiols
  • Spin Labels
  • Sulfhydryl Compounds
  • Nitric Oxide
  • S-Nitrosoglutathione
  • Mercaptoethanol
  • S-nitrosomercaptoethanol
  • 5,5-dimethyl-1-pyrroline-1-oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Glutathione
  • Penicillamine
  • Glutathione Disulfide