期刊
AAPS JOURNAL
卷 8, 期 3, 页码 E485-E492出版社
SPRINGER
DOI: 10.1208/aapsj080357
关键词
kinetics; nitric oxide; S-nitrosothiols; thiol; thiolate anion; S-transnitrosation
The reaction of sulfhydryl (SH)-containing molecules (thiols) with S-nitrosothiols (RSNO) has been shown to be of biological importance. Biologically or therapeutically relevant thiols generally have a pK(a) value ranging from 8 to 10 for the SH group. In addition, some of these thiols contain a carboxyl group and are acidic, which should be considered in studying the reaction between RSNO and thiols. In the present study, the kinetics of thiol-mediated decomposition of RSNO was investigated in a commonly used phosphate buffer, phosphate buffered saline (PBS; containing 6.9 mM phosphates; buffer capacity = 3.8 mM/pH). The thiols studied can be divided into 2 groups, depending on their pH perturbation capacity. The kinetics was studied using a wide range of thiol concentrations (ie, from 0.1 to 10 mM). A high-performance liquid chromatography (HPLC) method was used to determine RSNO concentrations. The results showed that the acidic thiols, including glutathione, captopril, N-acetylcysteine, and tiopronin, stimulated RSNO decomposition at low millimolar concentrations up to 2 mM. The stimulatory effect, however, became attenuated at concentrations higher than 2 mM in PBS. Increasing the concentration of acidic thiols caused a decrease in solution pH, which was attributable to the inhibitory effect at high thiol concentrations. The effect of thiols on the pH of reaction solution, and the resulting bell-shaped rate profiles, can be predicted by a quantitative analysis, from which a comparison of the intrinsic reactivity toward RSNO, among 8 thiols, was possible. The intrinsic reactivity in general followed the Bronsted relation.
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