Glutathione

What is Glutathione?

Glutathione (GSH) is a tripeptide consisting of glutamate, cysteine, and glycine joined by an unusual γ-glutamyl bond that resists most peptidases. It is the most abundant intracellular non-protein thiol in mammalian cells (millimolar concentrations) and serves as the primary cellular antioxidant and substrate for Phase II xenobiotic conjugation. Research-grade GSH is used as a reference substrate and supplement in cell-free and cell-based redox assays.

Mechanism of action (preclinical evidence)

Glutathione's mechanism rests on the redox chemistry of its cysteine thiol, which is the only highly nucleophilic and oxidation-prone group in the tripeptide. The free thiol (-SH) reacts directly with reactive oxygen species (hydrogen peroxide, hydroxyl radical, superoxide, peroxynitrite) and electrophilic intermediates, neutralizing them and forming the oxidized disulfide GSSG. GSSG is then reduced back to two molecules of GSH by glutathione reductase, using NADPH as the electron donor. This cycle - GSH oxidation, GSSG reduction - is one of the cell's most important redox-maintenance loops. Beyond direct radical scavenging, GSH serves as a cofactor for the glutathione peroxidase (GPx) family, which enzymatically reduces hydrogen peroxide and lipid peroxides at near-diffusion-limited rates. GSH also conjugates electrophilic xenobiotics through reactions catalyzed by glutathione-S-transferases (GSTs), forming water-soluble glutathione conjugates that are exported from cells via the multidrug resistance protein (MRP1/2) family and ultimately eliminated. This is the Phase II detoxification pathway. The GSH/GSSG ratio - typically >100:1 in healthy cells - is a sensitive indicator of redox state; a drop in this ratio is associated with oxidative stress in nearly every disease model. Glutathione is also a co-factor in glutaredoxin-mediated protein deglutathionylation and in the formation of certain protein-glutathione mixed disulfides that act as redox switches on regulatory proteins.

Research applications

• Oxidative stress models (hydrogen peroxide, superoxide, peroxynitrite)
• Cellular redox status measurement (GSH/GSSG ratio)
• Glutathione peroxidase and S-transferase enzyme assays
• Phase II drug metabolism and xenobiotic conjugation studies
• Mitochondrial function and apoptosis research

Storage and handling

Store lyophilised GSH at -20 °C in a sealed, light-protected vial - the cysteine thiol is highly susceptible to oxidation. Reconstitute in degassed buffer (often slightly acidic) and minimize air exposure. Adding chelators like EDTA can reduce metal-catalyzed oxidation in solution.

Regulatory status

Glutathione is sold as a dietary supplement in some jurisdictions but is not an approved therapeutic for any specific indication. Research-grade material is supplied by Peptra Labs for laboratory use only.

Frequently asked questions