Glutathione and low-molecular-weight thiols (GSH/LMWT)

Glutathione (GSH) is the primary low-molecular-weight thiol and the most abundant non-protein antioxidant in mammalian cells, playing a central role in maintaining redox homeostasis (1.2.1, 1.4.2). It functions as a critical buffer against oxidative stress by neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby protecting cellular components like DNA and proteins from damage (1.2.3, 1.3.2). Beyond its antioxidant capacity, GSH is essential for the detoxification of xenobiotics and drugs through conjugation reactions catalyzed by glutathione S-transferases (1.1.1, 1.5.1). Other low-molecular-weight thiols, such as cysteine and homocysteine, also contribute to the cellular thiol pool and influence signaling pathways related to cell proliferation and apoptosis (1.1.3, 1.4.3). In clinical contexts, the glutathione system is a significant therapeutic target due to its involvement in various pathologies. Elevated GSH levels in tumor cells are frequently associated with resistance to chemotherapy and radiation, leading to the development of depletion strategies like buthionine sulfoximine (BSO) to sensitize cancers (1.3.1, 1.3.5). Conversely, GSH deficiency is a hallmark of neurodegenerative diseases, liver injury, and chronic inflammation, where replenishment using precursors like N-acetylcysteine (NAC) is a standard intervention (1.3.2, 1.4.1). Monitoring the GSH/GSSG ratio serves as a vital biomarker for assessing cellular oxidative stress and the efficacy of redox-modulating therapies (1.2.3, 1.3.2).

Other names

GSHNon-protein thiolsLMW thiolsSulfhydryl compoundsReduced glutathione

Drugs modulate these thiols by replenishing levels via precursors (e.g., N-acetylcysteine), inhibiting de novo synthesis (e.g., buthionine sulfoximine), or depleting pools through conjugation and transport inhibition to induce oxidative stress or sensitize cells to therapy.