Glutathione (GSH)

Glutathione is a genuine tripeptide, composed of L-glutamate, L-cysteine and glycine, with the formula C10H17N3O6S and a molecular weight of 307.32 g/mol. Its structural signature is the gamma linkage: glutamate joins cysteine through its side-chain carboxyl group rather than the alpha-carboxyl used in ordinary protein backbones. That single feature makes the molecule resistant to most peptidases, which cannot recognise the unusual bond, and it is the reason glutathione persists intracellularly at millimolar concentrations instead of being degraded on contact with cytosolic proteases. It is the most abundant low-molecular-weight thiol in mammalian cells and is present in essentially every tissue examined.

The functional group that defines its chemistry is the free thiol on the cysteine residue. Two glutathione molecules can be oxidized to a disulfide-linked dimer, glutathione disulfide or GSSG, and the ratio of reduced to oxidized forms is the standard laboratory index of intracellular redox state. Glutathione is synthesised enzymatically in two ATP-dependent steps, by glutamate-cysteine ligase and then glutathione synthetase, and is not assembled on the ribosome from a genetic template the way protein-derived peptides are. That biosynthetic route is why it is classed as a non-ribosomal peptide. It is stocked here as a research reference compound only.

Glutathione was first isolated in 1888 by Joseph de Rey-Pailhade, who extracted a sulfur-containing reducing substance from yeast and called it philothion. Frederick Gowland Hopkins rediscovered and renamed the compound in 1921 and, across papers through the following decade, established that it is a tripeptide rather than a dipeptide. The gamma-glutamyl connectivity was confirmed by synthesis in the 1930s.

The modern literature is extensive. Meister and Anderson wrote the field-defining review of glutathione chemistry and metabolism (PubMed 6137189). Lu reviewed the two-enzyme biosynthetic route and its regulation (PubMed 22995213). Forman, Zhang and Rinna surveyed the measurement problem alongside biosynthesis (PubMed 18796312). Sies summarised glutathione’s cellular functions, including the glutathione peroxidase and S-transferase systems (PubMed 10569624).

Among the compounds catalogued on this site, glutathione has one of the most mature evidence bases. Its structure, biosynthesis, enzymology and analytical chemistry have been studied for over a century and are not in dispute. Less settled is anything downstream of the biochemistry: exogenous glutathione handling is complicated by extracellular hydrolysis, and outcome literature is inconsistent across models.

Published work describes glutathione as the principal low-molecular-weight thiol buffer of the cell. Its thiol donates reducing equivalents in reactions catalysed by glutathione peroxidases, and it forms conjugates with electrophilic compounds through glutathione S-transferases, the first step of a recognised detoxification route. Glutathione reductase then regenerates GSH from GSSG using NADPH, so the two cofactor systems are coupled (PubMed 10569624).

A distinction that is easy to miss: glutathione is a peptide but does not behave like the signalling peptides it is shelved beside. It has no receptor, and its activity is stoichiometric redox and conjugation chemistry. It is also frequently confused with N-acetylcysteine, which is a cysteine precursor, not glutathione itself. The rate-limiting factors in synthesis are cysteine availability and glutamate-cysteine ligase activity (PubMed 22995213).

The methodology caveat is unusually important here. GSH oxidises during sample handling, so a reported GSH/GSSG ratio depends heavily on how quickly the sample was quenched and whether thiols were blocked before analysis. Values from different assay platforms are not directly comparable (PubMed 18796312).

Lyophilized (freeze-dried) glutathione is stored at -20°C, shielded from light, and kept sealed until use. Repeated freeze-thaw cycles are avoided. No stability duration is asserted here; the data for a given lot are documented on its Certificate of Analysis.

Glutathione’s stability problem is the free thiol, which oxidises in air, faster at neutral to alkaline pH and with trace transition metals present. Dry sealed material is the stable state; in solution the reduced form converts toward GSSG. Because the oxidized dimer is a distinct chemical species, oxidation changes what is in the container, not just how much.

Reconstitution means returning a lyophilized compound to solution. No reconstitution procedure is given on this page. Solvent selection, quantities and technique belong to the methodology of the study protocol and to the documentation supplied with the lot.

As a general solubility class, glutathione is a freely water-soluble solid and does not require an organic co-solvent. Lyophilized material is hygroscopic, meaning it takes up atmospheric moisture, so containers stay closed while equilibrating to room temperature. Because ambient oxygen and trace metals drive thiol oxidation, open-container time is minimised. The lot Certificate of Analysis records appearance and identity.

For glutathione, the key documented parameter is oxidation state, not purity alone. Verified purity is documented per lot on the Certificate of Analysis, with identity confirmed by chromatographic and mass spectrometric methods. Check that the COA identifies the material as reduced glutathione rather than glutathione disulfide, and reconcile Section 1 against it.

House brand material from Novelle Bio and Catalyst Compounds is batch tested with a published Certificate of Analysis. Other brands carry the documentation supplied by their manufacturer. Because GSH and GSSG differ by two hydrogens and a disulfide bond, the mass spectrometric data on the COA confirms which species a lot contains.

Compounds researchers commonly study alongside glutathione:

• GHK-Cu.
  A copper-binding tripeptide studied in redox-linked tissue models, the closest short-peptide comparison in this catalog.
• NAD+.
  A non-peptide redox cofactor whose NADPH-linked chemistry regenerates reduced glutathione, so the two systems are measured together.
• KPV.
  Another tripeptide, the C-terminal fragment of alpha-MSH, with a signalling profile unrelated to redox chemistry.
• SS-31.
  A mitochondria-targeted tetrapeptide investigated in oxidative-stress models.
• Epitalon.
  A short peptide studied in ageing models where redox markers are reported.

Meister A, Anderson ME, et al. (1983). Glutathione. Annual Review of Biochemistry.
PubMed 6137189

Sies H, et al. (1999). Glutathione and its role in cellular functions. Free Radical Biology and Medicine.
PubMed 10569624

Wu G, Fang YZ, Yang S, et al. (2004). Glutathione metabolism and its implications for health. Journal of Nutrition.
PubMed 14988435

Forman HJ, Zhang H, Rinna A, et al. (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine.
PubMed 18796312

Lu SC, et al. (2013). Glutathione synthesis. Biochimica et Biophysica Acta.
PubMed 22995213

Peptides.com lists three glutathione research products across three brands, all supplied as lyophilized vials. Specifications are 600mg per vial for one listing and 1500mg per vial for the other two. No capsule or liquid spray format is stocked for this compound. Each lot is batch tested with a published Certificate of Analysis, available through Lab Reports.

• Browse all glutathione research products
• Catalyst Compounds Glutathione, 1500mg vial
• Novelle Bio Glutathione, 1500mg vial
• Real Peptides Glutathione, 600mg vial
• Collections: Research Vials. Documentation: COA and Lab Testing.

These products are sold for Research Use Only and are not intended for human consumption.