Selenium is an essential trace element incorporated into selenocysteine in selenoproteins. Glutathione peroxidase (GPx) is the most important selenoprotein for cellular antioxidant defense. How does GPx work in concert with glutathione reductase to maintain the cellular redox state?

• A GPx reduces H2O2 using NADPH directly, regenerating the selenol active site without glutathione participation
• B GPx converts H2O2 to superoxide using Fe2+, and glutathione reductase scavenges the superoxide
• C GPx and glutathione reductase compete for GSSG as substrate, with GPx winning at high H2O2 concentrations
• D GPx uses reduced glutathione (GSH) as electron donor to reduce H2O2 to water, producing oxidized glutathione (GSSG); glutathione reductase then uses NADPH to regenerate GSH from GSSG ✓

Explanation

Glutathione peroxidase (GPx) reduces H2O2 (and lipid hydroperoxides) to water using two molecules of reduced glutathione (GSH) as electron donors. The selenocysteine residue at the active site cycles between selenol (−SeH) and selenenylsulfide (−Se-SG) forms. The product is oxidized glutathione (GSSG). GSSG is then reconverted to two GSH molecules by glutathione reductase using NADPH as the electron source. The NADPH supply is maintained by the HMP/pentose phosphate pathway. This is why G6PD deficiency — by reducing NADPH production — impairs GPx function and leaves red cells vulnerable to oxidative hemolysis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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