Reactions of glutathionylcobalamin with nitroxyl and its donor, Angeli's salt.

We investigated the reaction between glutathionylcobalamin (GSCbl), a tight complex of cobalamin with glutathione (GSH), and nitroxyl (HNO) produced upon decomposition of Angeli's salt using ultraviolet-visible spectroscopy and ¹H NMR. The reaction in neutral and alkaline media leads to formation of nitrosylcobalamin (NOCbl). Simulation of the kinetic traces using the ChemMech program package suggested that the mechanism of the process involves complexation between HNO and GSCbl and further decomposition of the complex into the products. The complex participates in an acid-base equilibrium (pK_a = 8.9), and the deprotonated form decomposes to NOCbl more rapidly than the protonated species. At pH 7.4, the reaction of HNO with GSCbl proceeds ca.10³-times more slowly than with free GSH. GSCbl can react directly with the monoprotonated anion of Angeli's salt (HN₂O₃⁻) to produce nitrocobalamin (NO₂Cbl). The reaction between GSCbl and HN₂O₃⁻ is insignificant in an alkaline medium and is accelerated upon acidification of the medium. The critical step of the process is the complexation between GSCbl and HN₂O₃⁻. The produced complex is involved in an acid-base equilibrium (pK_a = 8.1): the protonated form can be transformed to NO₂Cbl and GSNHO⁻, whereas the deprotonated species decompose to initial reactants. [ABSTRACT FROM AUTHOR]