Glutathione (GSH) is the most abundant intracellular antioxidant (millimolar), a tripeptide of glutamate, cysteine, and glycine.Its activity comes from a single thiol group (-SH) on cysteine — this hydrogen can be donated to neutralize free radicals.
2 · The redox cycle
GPx uses two GSH to reduce H2O2 to water, turning them into GSSG, and glutathione reductase uses to turn GSSG back into two GSH.GSH is not disposable. Under glutathione peroxidase (GPx, a selenium enzyme), two GSH reduce H2O2 or lipid peroxides to water/alcohol, becoming GSSG (two GSH linked by a disulfide bond). Then glutathione reductase (GR) uses to reduce GSSG back to two GSH — the cycle repeats.
3 · Where NADPH comes from
The cycle's fuel is , mainly from the pentose phosphate pathway (PPP), key enzyme G6PD (glucose-6-phosphate dehydrogenase).So the GSH system is not isolated — it depends on glucose metabolism. Red blood cells have no nucleus or mitochondria and rely entirely on this pathway; that is why G6PD deficiency causes hemolysis.
4 · Does oral GSH work?
Most oral GSH is degraded by gut and liver /dipeptidases into amino acids; little enters blood intact.Witschi 1992: single 3000mg oral dose failed to raise blood GSH. Later trials with repeated low doses or liposomal forms show mild increases, but cost-effectiveness is far worse than: adequate protein (cysteine source), selenium (GPx cofactor), polyphenol-rich foods (upregulate endogenous GSH). is a cysteine prodrug useful in specific clinical settings.