Glutathione S-transferase enzyme (GST)

Glutathione S-transferase enzymes are a large family of multifunctional phase II metabolic enzymes found across eukaryotes and prokaryotes. Their primary role is the catalysis of the conjugation reaction between reduced glutathione (GSH) and a wide variety of electrophilic compounds—both endogenous toxins like peroxidized lipids as well as exogenous substances such as environmental toxins, herbicides, therapeutic drugs, and carcinogens—thereby increasing their water solubility for subsequent elimination from cells.[3][4] These enzymes exist mainly as cytosolic dimers but also have mitochondrial and microsomal forms. They exhibit significant diversity both structurally and functionally across different species. Beyond their canonical detoxifying role via GSH conjugation, some isoforms possess peroxidase activity that helps neutralize reactive oxygen species during oxidative stress,[5] while others participate non-catalytically in hormone transport or intracellular trafficking (“ligandin” function). The high inducibility under various stresses—including infection—makes them important players not only in chemical defense but also plant-pathogen interactions.[5] In humans, overexpression is linked to multidrug resistance in cancer cells due to enhanced clearance/inactivation of chemotherapeutics. The family includes several classes based on sequence similarity—such as alpha, mu, pi—and plant-specific classes like phi/tau. Genetic polymorphisms within these genes can influence susceptibility to diseases including cancer,[6] cardiovascular disorders,[2] neurodegeneration,[6] inflammation,[6], among others. Overall they represent key targets both for therapeutic intervention—to modulate drug metabolism/resistance—and biomarker development for personalized medicine approaches.[7][2][3]

Other names

LigandinGSTsGlutathione transferase

Drugs targeting or affected by GSTs typically act through one or more mechanisms: - Inhibition or modulation of enzymatic activity to overcome drug resistance in cancer therapy[7][2] - Enhancement or reduction of glutathione conjugation for improved drug clearance or toxicity management[2][7]