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

Glutathione Peroxidases (GPx) and Glutathione S-transferases (GST) are distinct families of enzymes that play central roles in cellular protection and detoxification by utilizing the tripeptide glutathione (GSH). GPx enzymes are primarily responsible for reducing hydrogen peroxide and organic hydroperoxides to water or alcohols, thereby preventing the formation of harmful free radicals and protecting cellular membranes from lipid peroxidation (PMID: 18511279). GSTs, on the other hand, catalyze the conjugation of GSH to a wide variety of endogenous and exogenous electrophilic compounds, facilitating their metabolism and eventual excretion from the body (PMID: 28633111). In clinical medicine, these enzymes are significant because their dysregulation is linked to various pathologies; for instance, GST overexpression is a hallmark of many cancers and contributes to chemotherapy resistance by neutralizing drugs before they reach their targets. Consequently, GST inhibitors like ezatiostat have been developed to enhance the efficacy of anticancer treatments. Conversely, GPx mimics such as ebselen are being explored for their ability to mitigate oxidative damage in conditions like noise-induced hearing loss and stroke (PubChem CID 3194). Together, these enzyme systems represent a critical nexus for therapeutic intervention in diseases driven by oxidative stress and chemical toxicity.

Other names

GPxGSTGlutathione-dependent antioxidant enzymesGlutathione-utilizing enzymesGSH-dependent enzymes

Glutathione peroxidases (GPx) reduce hydroperoxides to prevent oxidative damage, while Glutathione S-transferases (GST) conjugate glutathione to electrophilic xenobiotics to facilitate detoxification. Drugs targeting these enzymes either mimic GPx activity to lower oxidative stress or inhibit GST to prevent the metabolic inactivation of chemotherapeutic agents (PMID: 18511279, PMID: 28633111).