title: Mechanistic studies of S-nitrosothiol formation by NO*/O2 and by NO*/methemoglobin.
abstract: The mechanisms of formation of S-nitrosothiols under physiological conditions and, in particular, of generation of SNO-Hb (the hemoglobin form in which the cysteine residues beta93 are S-nitrosated) are still not completely understood. In this paper, we investigated whether, in the presence of O2, NO* is more efficient to nitrosate protein-bound thiols such as Cysbeta93 or low molecular weight thiols such as glutathione. Our results show that when substoichiometric amounts of NO* are mixed slowly with the protein solution, NO*, O2, and possibly NO2* and/or N2O3 accumulate in hydrophobic pockets of hemoglobin. Since the environment of the cysteine residue beta93 is rather hydrophobic, these conditions facilitate SNO-Hb production. Moreover, we show that S-nitrosation mediated by reaction of NO* with the iron(III) forms of Hb or Mb is significantly more effective when it can take place intramolecularly, as in metHb. Intermolecular reactions lead to lower S-nitrosothiol yields because of the concurring hydrolysis to nitrite.
authors.affiliation: Laboratorium für Anorganische Chemie, Eidgenössische Technische Hochschule, ETH Hönggerberg, CH-8093 Zürich, Switzerland. herold@inorg.chem.ethz.ch
authors.forename: Susanna
authors.initials: S
authors.lastname: Herold
authors.forename: Gabriele
authors.initials: G
authors.lastname: Röck
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry; D006736:Horses; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008706:Methemoglobin / Q000737:chemistry*; D008956:Models, Chemical; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry*; D009573:Nitrites / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D015538:Nitrosation; D009603:Nitroso Compounds / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010108:Oxyhemoglobins / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D026403:S-Nitrosothiols / Q000737:chemistry* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D010710:Phosphates; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; C100003:deoxyhemoglobin; D008706:Methemoglobin; D005978:Glutathione; D003545:Cysteine; D009584:Nitrogen; D010100:Oxygen