Glutathione (GSH) is the primary intracellular antioxidant peptide. Which enzyme regenerates GSH from GSSG (oxidized glutathione), and what is the essential cofactor?

• A Glutathione synthetase — ATP
• B Glutathione reductase — NADPH ✓
• C Glutathione peroxidase — selenium
• D Gamma-glutamyl transpeptidase — NAD+

Explanation

Oxidized glutathione (GSSG) is regenerated to GSH by glutathione reductase, which requires NADPH as the electron donor. NADPH is predominantly supplied by the hexose monophosphate (HMP) shunt via glucose-6-phosphate dehydrogenase (G6PD). In G6PD deficiency, NADPH is insufficient, glutathione reductase cannot regenerate GSH adequately, RBCs are susceptible to oxidative hemolysis. Glutathione peroxidase (option C, selenium-containing) uses GSH to reduce H2O2 and lipid peroxides, producing GSSG. Glutathione synthetase (option A) synthesizes GSH de novo (adding glycine to gamma-glutamylcysteine).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.