thiolredox

Thiolredox refers to the redox chemistry of thiol groups (R-SH) and their conversions to disulfides and other sulfur-containing oxidation states. It is central to protein function, antioxidant defense, and redox signaling. In aqueous solution at physiological pH, cysteine residues can lose a proton to form thiolate (R-S−), which is more reactive toward oxidants and disulfide formation. Two thiols can be oxidized to form a disulfide (R-S-S-R), a reaction that is often reversible by cellular reducing systems. The redox state of thiols in cells is commonly described by the glutathione couple GSH/GSSG, which has a standard redox potential around −240 mV at pH 7, though local environments can shift this value.

Biological thiolredox involves dedicated enzymatic systems. The thioredoxin system (thioredoxin, thioredoxin reductase, NADPH) and the glutathione system (glutathione reductase, glutaredoxins, and glutathione) maintain thiols in reduced forms and repair mixed disulfides. In the endoplasmic reticulum, protein disulfide isomerase catalyzes disulfide formation. Redox signaling arises from reversible modifications of cysteine residues, including sulfenylation (R-SOH), S-glutathionylation (R-S-SG), and S-nitrosylation (R-S-NO). Some overoxidations to sulfinic or sulfonic acids are reversible only in certain contexts or are considered oxidative damage.

Impacts of thiolredox span regulation of enzyme activity, transcription factors, and stress responses. Dysregulation is associated with aging, cancer, neurodegeneration, and inflammatory diseases. Measurement uses redox couples and redox-sensitive probes to assess cellular GSH/GSSG balance and cysteine oxidation states.