title: Generation of nitric oxide from S-nitrosothiols using protein-bound Cu2+ sources.
abstract: 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.
authors.affiliation: Department of Chemistry, Durham University, Durham DH1 3LE, UK. D.L.H.Williams@durham.ac.uk
authors.forename: A P
authors.initials: AP
authors.lastname: Dicks
authors.forename: D L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009603:Nitroso Compounds; D009842:Oligopeptides; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; C037026:diglycyl-histidine; D003300:Copper