Figure 1.

Cysteine (Cys) oxidation state is regulated intracellularly by the relative concentrations of reduced glutathione (GSH) and oxidized glutathione (glutathione disulfide dimer, GSSG). In a typical intracellular environment, high concentrations of reduced glutathione maintain cysteine in a thiol (Cys-SH) oxidation state. Under oxidizing conditions, including oxidative stress, increased concentrations of GSSG lead to increased levels of cysteine disulfides, including glutathionylated cysteine via reaction of the nucleophilic cysteine with the electrophilic glutathione disulfide via disulfide exchange. Alternatively, glutathionylated cysteine may also be generated via oxidation of cysteine to the sulfenic acid followed by reaction of the electrophilic sulfenic acid with nucleophilic glutathione. In addition, cysteine glutathionylation may be effected via free radical (not shown) or enzymatic mechanisms.^{36, 38, 39}