Glutathione synthesis and oxidative stress pathways (GSH/ROS pathways)

The glutathione synthesis and oxidative stress pathways are fundamental biological processes that maintain cellular redox balance and protect against damage from reactive oxygen species (ROS) (StatPearls: NBK557611). Glutathione (GSH), the most abundant intracellular thiol, is synthesized in two ATP-dependent steps catalyzed by glutamate-cysteine ligase (GCL) and glutathione synthetase (GSS) (Wikipedia: Glutathione). These pathways are central to detoxification and the regulation of various cellular processes, including apoptosis and signal transduction (PubMed: 25688613). In disease states, oxidative stress arises from an imbalance between ROS production and antioxidant capacity, contributing to the progression of cancer, neurodegeneration, and cardiovascular disorders (NIH: Oxidative Stress). Pharmacological intervention often targets these pathways by either enhancing antioxidant defenses through Nrf2 activation or GSH precursors like N-acetylcysteine, or by depleting GSH using inhibitors like buthionine sulfoximine to overcome chemoresistance in tumors (PubChem: N-acetylcysteine).

Other names

GSH metabolismRedox homeostasisAntioxidant response pathwayCellular oxidative stress response

Drugs targeting these pathways typically act by providing biosynthetic precursors (e.g., N-acetylcysteine for cysteine), inhibiting rate-limiting enzymes like glutamate-cysteine ligase (e.g., buthionine sulfoximine), or activating transcription factors such as Nrf2 to upregulate a suite of antioxidant and detoxification genes (StatPearls: NBK557611; PubMed: 25688613).