Glutathione Peroxidase (GPx): Types and Functions, Mechanism, Clinical Significance

• Glutathione Peroxidase (GPx) is a family of enzymes that protect organisms from oxidative damage by reducing hydrogen peroxide, organic hydroperoxides, and lipid peroxides to water and corresponding alcohols, using glutathione (GSH) as a reducing agent.

2GSH + H2​O2 ​→ GSSG + 2H2​O 

2GSH + ROOH → GSSG + ROH + H2​O

Types and Functions

• GPx1: The most common cytosolic enzyme that reduces hydrogen peroxide.

• GPx4: Unique for its ability to directly reduce lipid peroxides within biological membranes, protecting against lipid peroxidation.

• The GPx family includes isoforms in the mitochondria (GPx1 and GPx4) and the extracellular space (GPx3), indicating their role in managing oxidative stress across different cell compartments.

Mechanism

• GPx uses glutathione (GSH), converting it to glutathione disulfide (GSSG) in the process of reducing peroxides.

• Glutathione reductase then regenerates GSH from GSSG using NADPH as an electron donor, maintaining a reduced glutathione pool for continuous antioxidant defense.

Clinical Significance

• Selenium is a vital cofactor for some GPx enzymes.

• Selenium deficiency can decrease GPx activity, increasing susceptibility to oxidative stress.

• GPx activity is crucial for preventing oxidative damage to lipids, proteins, and nucleic acids, with dysfunction linked to diseases like cancer, cardiovascular diseases, and neurodegenerative disorders.