Generation of nitric oxide from S-nitrosothiols using protein-bound Cu2+ sources

Chem Biol. 1996 Aug;3(8):655-9. doi: 10.1016/s1074-5521(96)90133-7.


Background: We have recently shown that S-nitrosothiols (RSNOs) decompose in aqueous buffer to give nitric oxide, an important signalling molecule, and the corresponding disulphides. This occurs by reaction with Cu+ generated from Cu2+ (supplied as hydrated Cu2+) by thiolate reduction. To establish whether these reactions are feasible in vivo, we set out to determine whether Cu2+ bound to an amino acid, a tripeptide or to human serum albumin (HSA) could serve as a Cu+ source for generation of NO from S-nitrosothiols.

Results: Experiments with Cu2+ bound to the tripeptide Gly-Gly-His or to two histidine molecules or to HSA showed that Cu+ was released (and trapped with neocuproine) when the copper source was treated with a thiol at pH 7.4. RSNO decomposition was achieved with all three copper sources, although not as rapidly as with added hydrated Cu2+. Decomposition was also catalyzed by ceruloplasmin.

Conclusions: These results show clearly that amino-acid- and protein-bound Cu2+ can be reduced by thiolate ion to Cu+, which will generate NO from RSNO species, thus providing a realistic model for these reactions in vivo.

MeSH terms

  • Copper / chemistry
  • Copper / metabolism*
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Nitric Oxide / chemistry
  • Nitric Oxide / metabolism*
  • Nitroso Compounds / chemistry
  • Nitroso Compounds / metabolism*
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Oxidation-Reduction
  • Protein Binding
  • Serum Albumin / chemistry
  • Serum Albumin / metabolism
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / metabolism*


  • Nitroso Compounds
  • Oligopeptides
  • Serum Albumin
  • Sulfhydryl Compounds
  • Nitric Oxide
  • diglycyl-histidine
  • Copper