Glutathione

Glutathione (GSH) is a tripeptide composed of glutamate, cysteine, and glycine that exists primarily in its reduced (thiol) form within cells. It functions as the body’s master antioxidant, maintaining redox balance, detoxifying reactive species, and supporting enzymatic processes essential for health.

Glutathione (reduced) is a tripeptide: γ‑L‑glutamyl‑L‑cysteinyl‑glycine.

• Molecular formula: C₁₀H₁₇N₃O₆S (M ≈ 307.32 g mol⁻¹)
• IUPAC name: (2S)-2‑Amino‑4‑[(2‑S‑[[(2‑S‑[[(2‑S‑{(2‑amino‑2‑carboxyethyl)‑(2‑sulfo‑1‑yl)‑2‑hydroxy‑1‑carboxy‑ethyl]‑amino)‑2‑hydroxy‑2‑methyl‑propane‑1‑yl]‑amino]‑2‑hydroxy‑3‑oxopropyl]‑amino]‑butanoic acid (commonly given as γ‑L‑glutamyl‑L‑cysteinyl‑glycine).
• Key structural features: a γ‑peptide bond linking glutamate’s γ‑carboxyl to cysteine’s amino group; a free thiol on cysteine (the active antioxidant moiety); and a C‑terminal glycine, which facilitates transport across cellular membranes via the peptide transporter PEPT1/2.
• Water Solubility: The molecule is highly water-soluble (pKa ≈ 9.2 for the thiol) and exists in a dynamic equilibrium between reduced (GSH) and oxidized (GSSG) forms.

• Natural glutathione is harvested from yeast (Saccharomyces cerevisiae) and bacterial cultures (e.g., Bacillus subtilis) using fermentation, followed by purification via ion‑exchange and crystallization.
• Reduced glutathione: Commercial supplements often use reduced glutathione produced by controlled microbial fermentation, which yields a high‑purity (> 98 %) product.
• Synthetic GSH: An alternative is synthetic GSH, chemically assembled from the three amino acids under controlled conditions; however, the fermentation method is preferred for its lower impurity profile and better stereospecificity.
• Bioavailability Enhancement: For oral supplements, many manufacturers employ liposomal encapsulation or sublingual buccal delivery to enhance bio‑availability.
• Quality Considerations: Quality considerations include verification of the reduced (GSH) to oxidized (GSSG) ratio (< 5 % GSSG), absence of heavy metals, and compliance with pharmacopeial standards (USP, EP). Third‑party testing (e.g., NSF, USP) is recommended to ensure potency and purity.