Glutathione Peroxidase 3 (GPX3), also known as plasma glutathione peroxidase (GPx-P) or extracellular glutathione peroxidase, is an enzyme encoded by the GPX3 gene in humans . It belongs to the glutathione peroxidase family, which plays a crucial role in protecting cells from oxidative damage by reducing hydrogen peroxide, lipid peroxides, and organic hydroperoxides .
GPX3 contains a selenocysteine (Sec) residue at its active site, which is essential for its enzymatic activity . The selenocysteine is encoded by the UGA codon, which typically signals translation termination. However, in the case of Sec-containing genes, a specific stem-loop structure in the 3’ untranslated region (UTR), known as the Sec insertion sequence (SECIS), allows the UGA codon to be recognized as a Sec codon instead of a stop signal .
GPX3 functions as an oxidoreductase enzyme, catalyzing the conversion of hydrogen peroxide into water, thereby mitigating oxidative damage . It has a wide thiol specificity, with sources of reducing power including glutathione (GSH), cysteine, mercaptoethanol, and dithiothreitol . In vitro studies have shown that GSH can be completely replaced by reduced homocysteine for GPX3 activity .
GPX3 is primarily found in the extracellular space, including blood plasma, and is involved in detoxifying hydrogen peroxide in the extracellular environment . It plays a vital role in maintaining the redox balance and protecting cells from oxidative stress . Beyond its antioxidant function, GPX3 is also involved in regulating metabolism, modulating cell growth, inducing apoptosis, and facilitating signal transduction .
Recent studies have highlighted the significance of GPX3 in various non-neoplastic diseases. Aberrant expression of GPX3 has been associated with multiple pathological processes, including cardiovascular diseases, metabolic disorders, and inflammatory conditions . Additionally, GPX3 serves as a significant tumor suppressor in various cancers, making it a potential diagnostic biomarker and therapeutic target .
Recombinant human GPX3 is produced using recombinant DNA technology, allowing for the large-scale production of this enzyme for research and therapeutic purposes . Recombinant GPX3 retains the same structure and function as the naturally occurring enzyme, making it a valuable tool for studying oxidative stress and developing potential treatments for diseases associated with oxidative damage .