Formation of S-nitrosothiols from regiospecific reaction of thiols with N-nitrosotryptophan derivatives.
S-nitrosothiols transport nitric oxide in vivo, and so-called transnitrosation reactions (i.e. the transfer of the nitroso function from nitrosothiol to thiolate) are believed to be involved in this process. In the present study we examined the N-nitrosotryptophan derivative-dependent nitrosation of thiols, a hitherto ignored possibility for the formation of S-nitrosothiols. The corresponding products were identified by (15)N-NMR spectrometry. The fact that the reaction proceeded under hypoxic conditions as well as in non-aqueous solution strongly indicated the occurrence of a transnitrosation reaction. Interestingly, S-nitrosothiols could only very slowly transnitrosate N-terminal-blocked tryptophan derivatives like melatonin in non-aqueous solution but did not induce such a reaction in water. The indole moiety of the N-nitrosotryptophan derivatives was fully restituted during the reaction with thiols, as demonstrated by both capillary zone electrophoresis and fluorescence spectroscopy. A determination of the Arrhenius parameters demonstrated that the corresponding rate constants were comparable with the ones known for the transfer of the nitroso function from nitrosothiol to thiolate. Thus, N-nitrosotryptophan-dependent nitrosation of thiols may occur in vivo and might offer the possibility of developing a new class of vasodilative drugs.
Sonnenschein
Kristina
K
Institut für Physiologische Chemie, Universitätsklinikum, Hufelandstrasse 55, 45122 Essen, Germany.
de Groot
Herbert
H
Kirsch
Michael
M
D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015538:Nitrosation; D026403:S-Nitrosothiols / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D014364:Tryptophan; D005978:Glutathione; D003545:Cysteine