General cellular thiol-containing proteins and glutathione pool (GSH/Thiol pool)

The general cellular thiol-containing proteins and glutathione pool represent the primary redox buffer and detoxification system within the cell (PubChem, CID 124886). This pool consists of the tripeptide glutathione (GSH) and various proteins containing reactive cysteine residues, which together maintain the intracellular environment in a reduced state and facilitate proper protein folding (NIH, PMC4684116). These thiols play a critical role in neutralizing reactive oxygen species (ROS) and electrophilic xenobiotics, thereby protecting cellular macromolecules from oxidative damage (StatPearls, NBK557637). In clinical pharmacology, this pool is a significant target for drugs like acetaminophen, which can deplete GSH leading to hepatotoxicity, and N-acetylcysteine, which serves as a precursor to replenish it (PubMed, 25601602). Furthermore, elevated thiol levels in cancer cells are often associated with resistance to platinum-based chemotherapies and alkylating agents, as these drugs are sequestered and inactivated by conjugation with GSH (PubMed, 15474335). Understanding the dynamics of this pool is essential for managing drug toxicity and overcoming therapeutic resistance in oncology.

Other names

Cellular thiol poolNon-protein thiolsProtein-bound thiolsEndogenous antioxidant poolIntracellular glutathione system

Drugs interact with this pool primarily through covalent conjugation to the sulfhydryl (-SH) groups of glutathione or reactive cysteine residues in proteins, leading to the detoxification of electrophiles, sequestration of heavy metals, or depletion of the cell's antioxidant capacity (StatPearls, NBK557637).