Glutathione S-transferase and related peroxidases (GST/GPx)

Glutathione S-transferases (GSTs) and related peroxidases, such as glutathione peroxidases (GPxs), are a diverse group of enzymes essential for cellular detoxification and the maintenance of redox homeostasis. GSTs primarily catalyze the conjugation of reduced glutathione (GSH) to a wide variety of endogenous and exogenous electrophilic compounds, facilitating their excretion and protecting cells from chemical insult [1][2]. GPxs complement this by reducing hydrogen peroxide and organic hydroperoxides to water or alcohols, thereby preventing oxidative damage to lipids and proteins [3]. In clinical oncology, GSTs—particularly the Pi class (GSTP1)—are frequently overexpressed in various tumors, where they contribute to multi-drug resistance by detoxifying chemotherapeutic agents and inhibiting pro-apoptotic signaling pathways [4]. Consequently, these enzymes are targeted by inhibitors designed to sensitize cancer cells to chemotherapy or by prodrugs that are selectively activated by GST activity [5]. Beyond cancer, the antioxidant functions of GPxs are explored in the context of neurodegenerative and cardiovascular diseases, where GPx mimics like ebselen are investigated for their potential to mitigate oxidative stress-induced injury [6].

Other names

GSTsGPxsGlutathione-dependent enzymesLigandinGlutathione peroxidaseGlutathione S-transferase

Inhibition of GST enzymes to reverse chemotherapy resistance; activation of prodrugs by GST overexpressing cells; mimetic activity of GPx to reduce oxidative stress; modulation of JNK signaling pathways via GSTP1 interaction.