Mechanism of nitric oxide release from S-nitrosothiols.
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.
Singh
R J
RJ
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Hogg
N
N
Joseph
J
J
Kalyanaraman
B
B
D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D019803:Glutathione Disulfide; D007700:Kinetics; D008623:Mercaptoethanol; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives; D010782:Photolysis; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione; D026403:S-Nitrosothiols; D013113:Spin Labels; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism
D003497:Cyclic N-Oxides; D005609:Free Radicals; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013113:Spin Labels; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D005978:Glutathione; D010396:Penicillamine; D019803:Glutathione Disulfide