Cellular proteins and thiol-containing biomolecules

Cellular proteins and thiol-containing biomolecules represent a broad class of endogenous molecules characterized by the presence of reactive sulfhydryl (-SH) groups. The most prominent small-molecule member is glutathione (GSH), which serves as the primary antioxidant and detoxification agent within the cell, protecting against oxidative stress and electrophilic insults (PubChem, CID 124886). Protein thiols, particularly cysteine residues, are essential for maintaining protein tertiary structure through disulfide bonds and for the catalytic activity of numerous enzymes (PubMed, PMID 22503473). In pharmacology and toxicology, these molecules are often the unintended targets of reactive electrophilic metabolites or heavy metals, which form covalent adducts with the sulfur atom. For example, the acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) depletes glutathione and binds to cellular proteins, leading to hepatic necrosis (StatPearls, NBK441917). Conversely, therapeutic agents like N-acetylcysteine are used to replenish these thiol pools to mitigate oxidative stress and toxicity (NIH, LiverTox).

Other names

Sulfhydryl-containing moleculesProtein thiolsThiol-containing compoundsEndogenous thiolsCysteine-rich proteins

Drugs or their reactive metabolites interact with these biomolecules through covalent binding to sulfhydryl (-SH) groups, leading to the depletion of antioxidant capacity (e.g., glutathione depletion) or the functional inactivation of critical cellular proteins.