Glutathione peroxidase (GPx) and glutathione S-transferase (GST) (GPx/GST)

Glutathione peroxidases (GPx) and glutathione S-transferases (GST) represent two essential enzyme families that utilize the tripeptide glutathione (GSH) to protect cells from oxidative damage and chemical insults (UniProt P07203; StatPearls NBK557537). GPxs are antioxidant enzymes that reduce hydrogen peroxide and organic hydroperoxides to water or alcohols, with GPx4 playing a pivotal role in preventing ferroptosis, a form of regulated cell death (PubMed 24439385). GSTs are phase II metabolic enzymes that catalyze the conjugation of GSH to electrophilic substances, facilitating their excretion and detoxification (PubMed 28671666). In oncology, GSTs—particularly the Pi class (GSTP1)—are frequently overexpressed, leading to chemotherapy resistance by neutralizing drugs before they reach their targets (DrugBank DB06025). Conversely, a deficiency in GPx activity is associated with increased susceptibility to neurodegenerative and cardiovascular diseases due to unchecked oxidative stress (PubMed 30261569). Therapeutic interventions include GPx mimics like Ebselen for neuroprotection and GST inhibitors like Ezatiostat to overcome drug resistance in cancer (PubChem CID 3194).

Other names

GPxsGSTsGSH-PxGlutathione-dependent enzymesGlutathione-S-transferase

GPx mimics reduce oxidative stress by catalyzing the reduction of peroxides; GST inhibitors prevent the conjugation of glutathione to chemotherapeutic drugs, thereby increasing drug efficacy in resistant tumors. GPx4 inhibitors induce ferroptosis in cancer cells.