Two-Electron Reduction of Nitrosonium Species by Glutathione

This shows a proposed mechanism for the two-electron reduction of a nitrosonium (an oxoammonium cation), derived from an acetohydroxamic acid (shown protonated in the product, despite the unlikelihood of that), to an acetohydroxylamine (a.k.a. an acetohydroxamic acid) by glutathione, to form oxidized glutathione (GSSG). The overall mechanism is similar to the mechanism shown by Arends et al. (2006) [Arends et al., 2006: (http://cat.inist.fr/?aModele=afficheN&cpsidt=17844353)] for the two-electron reduction of an oxoammonium species by an alcohol, in the presence of a base. Boese et al. (1997) [Boese et al., 1997: (http://www.jbc.org/content/272/35/21767.full.pdf+html)(http://www.ncbi.nlm.nih.gov/pubmed/9268306?dopt=Abstract)] and Li et al. (2005) [Li et al., 2005: (http://www.jbc.org/content/280/17/16594.full.pdf+html)(http://www.ncbi.nlm.nih.gov/pubmed/15695823?dopt=Abstract)] also discussed mechanisms for reactions involving nitrosothiols, and those mechanisms are likely to be applicable in this case. There's evidence that the two-electron reduction of oxoammonium species, formed by the one-electron oxidation of nitroxide radicals, is going to be the predominant reduction pathway in vivo, even (and, in fact, particularly) during hypoxia or metabolic stress. In vitro, the one-electron reduction does occur, and the two-electron reduction also may occur.