Nitrosation, Thiols, and Hemoglobin: Energetics and Kinetics

Abstract

Nitrosothiols are powerful vasodilators. Although the mechanism of their formation near neutral pH is an area of intense research, neither the energetics nor the kinetics of this reaction or of subsequent reactions have been addressed. The following considerations may help to guide experiments. (1) The standard Gibbs energy for the homolysis reaction RSNO → RS• + NO•(aq) is +110 ± 5 kJ mol–1. (2) The electrode potential of the RSNO, H+/RSH, NO•(aq) couple is −0.20 ± 0.06 V at pH 7. (3) Thiol nitrosation by NO2– is favorable by 37 ± 5 kJ mol–1 at pH 7. (4) N2O3 is not involved in in vivo nitrosation mechanisms for thermodynamic — its formation from NO2– costs 59 kJ mol–1 — or kinetic — the reaction being second-order in NO2– — reasons. (5) Hemoglobin (Hb) cannot catalyze formation of N2O3, be it via the intermediacy of the reaction of Hb[FeNO2]2+ with NO• (+81 kJ mol–1) or reaction of Hb[FeNO]3+ with NO2– (+88 kJ mol–1). (6) Energetically and kinetically viable are nitrosations that involve HNO2 or NO• in the presence of an electron acceptor with an electrode potential higher than −0.20 V. These considerations are derived from existing thermochemical and kinetics data.

Reactions of superoxide dismutases with HS−/H2S and superoxide radical anion: An in vitro EPR study

“…A wide range of redox midpoint potentials (120-525 mV) has been reported for bovine CuZnSOD [32]. Although we could not find a reliable information on redox potential for rat CuZnSOD, it is unlikely to be higher than 920 mV, which is the redox potential for one electron oxidation of HS - [16]. On the other hand, two-electron redox potential of HS -(reaction: HS -→ S 0 + H + + 2e -) at pH 7 is 170 mV [33], which makes HS --induced reduction of Cu 2+ ZnSOD feasible.…”

“…This is in line with the available data on redox potentials. Namely, redox midpoint potential of FeSOD (~100 mV) is lower compared to redox potential of HS -(920 mV at pH 7.4; reaction: HS -→ HS • + e -; the same potential applies to H 2 S → HS • + H + + e -) [9,16,17]. The resistance of FeSOD to reduction appears to be in line with its role in the early evolution of life that took place under the reducing conditions [9].…”

Mechanisms of Human Erythrocytic Bioactivation of Nitrite

“…Thus, based on an analysis of these rate constants, NO formed in the red blood cell is not likely to escape scavenging. Several pathways have been proposed that could potentially lead to the export of NO activity from the red cell (19 -27), but none of these proposed mechanisms has been proven, and all have been challenged (28,29).…”

Mechanisms of Nitric Oxide Reactions Mediated by Biologically Relevant Metal Centers

“…However, it is important to recognize that the driving force of the reductive nitrosylation of the heme proteins and models at near neutral pH is the very great stability of the ferrous nitrosyl complexes formed under excess NO. In the absence of excess NO, the reverse reaction, namely, nitrite reduction by the ferrous complexes, is thermodynamically favored [117,123]. The nitrosyl complex of metMb has also been reported to react with the biological antioxidant glutathione GSH (in the presence of excess NO) to give Mb(NO) and S-nitrosoglutathione (GSNO) [124].…”