Cellular thiols (GSH)

Cellular thiols, primarily represented by the tripeptide glutathione (GSH), serve as the fundamental redox buffer within the intracellular environment, maintaining the balance between reduced and oxidized states. These molecules are characterized by reactive sulfhydryl (-SH) groups that participate in thiol-disulfide exchange reactions, which are essential for protein folding, enzyme regulation, and protection against oxidative stress (Meister, A., 1988, J. Biol. Chem.; Forman, H. J., et al., 2009, Mol. Aspects Med.). In a pharmacological context, cellular thiols act as the functional target for disulfide-based drugs like cystamine. Upon cellular entry, cystamine undergoes a non-enzymatic thiol-disulfide exchange with endogenous GSH, resulting in the release of cysteamine (PubChem CID 311). This mechanism is the basis for treating cystinosis, a lysosomal storage disorder; the released cysteamine reacts with accumulated lysosomal cystine to form a mixed disulfide that can exit the lysosome via the PQLC2 transporter (Gahl, W. A., et al., 2002, N. Engl. J. Med.). Additionally, the interaction with cellular thiols is investigated for neuroprotective effects in diseases like Huntington's, where cystamine may inhibit transglutaminase or modulate antioxidant responses (Karpuj, M. V., et al., 2002, Nat. Med.). Monitoring the balance of these thiol pools is crucial, as excessive depletion can lead to oxidative stress and cellular damage.

Other names

Endogenous thiolsIntracellular sulfhydryl groupsGlutathione poolNon-protein thiolsIntracellular thiols

Thiol-disulfide exchange leading to the release of active thiol moieties (e.g., cysteamine)