What is glutathione?
Glutathione is a tripeptide. Its full name is gamma-L-glutamyl-L-cysteinyl-glycine. Its reduced form is written GSH. Nearly all eukaryotic cells contain it, as do many prokaryotes. In both, it occurs at millimolar concentrations. In animals, it is made in the cytosol (Oestreicher and Morgan, 2019). Glutathione is the low molecular weight thiol that cells make in the largest amount. It protects cells against oxidants and reactive electrophiles (Forman et al., 2009).
Its first bond is unusual. Glutamate joins cysteine through its side-chain (gamma) carboxyl group. Ordinary peptide bonds use the alpha carboxyl group. A dedicated cell-surface enzyme, gamma-glutamyl transpeptidase, cleaves this gamma bond (Hanigan, 2014). Disguised Alpha supplies L-glutathione as a lyophilized powder and as a solution, for laboratory research use only. Nothing on this page is guidance for use in people.
Glutathione reference data
| Property | Value |
|---|---|
| Name | L-Glutathione (reduced glutathione, GSH) |
| Sequence | gamma-L-Glu-L-Cys-Gly: glutamate linked through its gamma carboxyl group (PubChem CID 124886) |
| Molecular formula | C₁₀H₁₇N₃O₆S |
| Molecular weight | 307.33 g/mol |
| CAS number | 106272-20-2 (PubChem CID 124886 lists this number and 70-18-8 for glutathione) |
| Oxidized form | Glutathione disulfide (GSSG), two GSH molecules joined by a disulfide bond |
| Formats carried | Lyophilized powder, 1,500 mg per vial (L-Glutathione); solution, 200 mg/mL in 20 mL (200MG/ML solution) |
| Storage | Powder: -20°C, protected from light; 2 to 8°C after reconstitution. Solution: 15 to 25°C unopened. Do not freeze. Keep in a fridge once opened |
| Testing | Tested by a third party. Certificates for each lot are published on each product page and in the COA portal |
Formula, molecular weight and CAS number come from the two product pages. Amounts and storage also come from these pages. The sequence comes from PubChem. Check identity and measured content against your lot's certificate.
What the research covers
The glutathione literature is very large. The studies below cover six areas. Each summary states the model used.
Synthesis and breakdown
Cells make glutathione in the cytosol in two steps. The first uses glutamate-cysteine ligase. This is the rate-limiting enzyme, earlier called gamma-glutamylcysteine synthetase. The second uses glutathione synthetase. The main controls are the supply of cysteine and how active the ligase is. The genes respond to transcription factors, including Nrf2 (Lu, 2013).
In work with the purified enzyme, glutathione inhibited its own synthesis. It acted through non-allosteric feedback on gamma-glutamylcysteine synthetase (Richman and Meister, 1975). Breakdown starts outside the cell. Gamma-glutamyl transpeptidase releases glutamate. Cell-surface dipeptidases cleave the cysteinyl-glycine that is left (Hanigan, 2026). Models: purified enzymes, cell and animal biochemistry, reviews.
The GSH/GSSG redox couple
The GSSG/2GSH couple is the redox couple found in the largest amount in a cell. The Nernst equation was used to estimate its half-cell reduction potential. This value was tied to the state of the cell. It was about -240 mV in proliferating cells.
It was -200 mV in differentiating cells and -170 mV in apoptotic cells (Schafer and Buettner, 2001). Compartments differ. A peptide probe was trapped in the secretory pathway. The GSH/GSSG ratio there was 1:1 to 3:1. The whole-cell ratio was 30:1 to 100:1 (Hwang et al., 1992). Models: redox theory and cultured cells.
Enzymes that use glutathione
Mammals have eight enzymes called glutathione peroxidases, GPx1 to GPx8. These enzymes remove hydroperoxides. Studies report a role for GPx1 in insulin signalling. They also report roles for GPx4 in apoptosis and male fertility (Brigelius-Flohé and Maiorino, 2013). Glutathione transferases attach glutathione to electrophilic xenobiotics. They also attach it to oxidative stress products such as 4-hydroxynonenal.
Tests with disrupted genes in mice showed that the cytosolic enzymes broadly protect cells. They are cytoprotective (Hayes et al., 2005). Glutathione can also attach to protein cysteine residues. This is a change made after translation, a post-translational modification. It is called S-glutathionylation (Dalle-Donne et al., 2009). Models: enzymology, knockout mice, reviews.
Depletion as an experimental tool
Much of the evidence on glutathione's function comes from removing it. Buthionine sulfoximine was about 20 times more effective than prothionine sulfoximine at inhibiting gamma-glutamylcysteine synthetase. It lowered kidney glutathione in mice to under 20% of control (Griffith and Meister, 1979). In cancer cells, erastin blocks cystine uptake through the cystine/glutamate antiporter, system xc-.
It triggers iron-dependent, non-apoptotic cell death. The authors named this ferroptosis (Dixon et al., 2012). Follow-up work showed that glutathione depletion stops glutathione peroxidases from working. Another class of compounds inhibits GPX4 directly. This work also profiled how sensitive 177 cancer cell lines were (Yang et al., 2014). Models: purified enzyme, mice, cancer cell lines, xenograft mice.
Measuring GSH and GSSG
The common enzymatic recycling assay uses DTNB to read GSH at 412 nm. Glutathione reductase and NADPH recycle GSSG back to GSH (Rahman et al., 2006). Sample handling is the main source of error. In human blood, oxidation during acid deproteinization made GSSG values seem too high. Oxidation after neutral to alkaline pH was restored did the same.
The authors concluded that artifacts may affect most published GSSG data (Rossi et al., 2002). Derivatizing GSH with N-ethylmaleimide before deproteinization prevents artifactual oxidation. Without this step, oxidation affects 5 to 15% of the GSH in a sample (Giustarini et al., 2013). Models: analytical methods, human blood.
Oral glutathione in healthy volunteers
Human studies of oral glutathione do not agree. In 7 healthy volunteers, a single oral amount did not cause a significant rise in plasma glutathione over 270 minutes. The authors attributed this finding to hydrolysis by gamma-glutamyltransferase in the intestine and liver (Witschi et al., 1992). A 4-week trial studied 40 healthy adults. The trial was randomized and placebo-controlled.
It found no change in oxidative stress biomarkers or glutathione status (Allen and Bradley, 2011). A 6-month trial studied 54 non-smoking adults. The trial was randomized and placebo-controlled. It reported higher glutathione in blood, erythrocytes and plasma. Glutathione was also higher in lymphocytes and buccal cells. Levels returned to baseline after a 1-month washout (Richie et al., 2015). Model: healthy human volunteers.
Key studies
- Oestreicher J, Morgan B. "Glutathione: subcellular distribution and membrane transport (1)." Biochem Cell Biol. 2019. PMID 30427707. DOI 10.1139/bcb-2018-0189. Review: structure, concentrations and compartments.
- Lu SC. "Glutathione synthesis." Biochim Biophys Acta. 2013. PMID 22995213. DOI 10.1016/j.bbagen.2012.09.008. Review: the two synthetic enzymes and their regulation.
- Schafer FQ, Buettner GR. "Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple." Free Radic Biol Med. 2001. PMID 11368918. DOI 10.1016/s0891-5849(01)00480-4. Redox theory of the GSSG/2GSH couple.
- Griffith OW, Meister A. "Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine)." J Biol Chem. 1979. PMID 38242. Purified enzyme and mice: a depletion tool.
- Yang WS, et al. "Regulation of ferroptotic cancer cell death by GPX4." Cell. 2014. PMID 24439385. DOI 10.1016/j.cell.2013.12.010. Cancer cell lines and xenograft mice.
- Richie JP Jr, et al. "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione." Eur J Nutr. 2015. PMID 24791752. DOI 10.1007/s00394-014-0706-z. Healthy adults: 6-month randomized trial.
Handling and storage of lyophilized glutathione
General laboratory practice for this material:
- Store the lyophilized powder at -20°C, protected from light, until use (storage guidance on the product page).
- Let the sealed vial reach room temperature before opening. This prevents moisture from condensing on the powder.
- Thiol oxidation to GSSG during handling is a known source of error (Giustarini et al., 2016). This includes oxidation after neutral to alkaline pH is restored (Rossi et al., 2002). Prepare solutions fresh and keep them cold.
- For GSH/GSSG measurements, block the thiol with N-ethylmaleimide before acid deproteinization (Giustarini et al., 2013).
- After reconstitution, keep solutions at 2 to 8°C and protected from light. Use single-use aliquots. Avoid freeze/thaw cycles.
- The 200 mg/mL solution is listed for 15 to 25°C unopened. Do not freeze it. Once opened, keep it in a fridge and protected from light (product page).
- Record the lot number. For quantitative work, use the measured content on the certificate. Use this value rather than the label mass.
Frequently asked questions
Is glutathione a peptide?
Yes. It is a tripeptide of glutamate, cysteine and glycine (Oestreicher and Morgan, 2019). It is atypical. Glutamate links to cysteine through its side-chain gamma carboxyl group. Standard peptide bonds use the alpha carboxyl group. Two dedicated enzymes assemble the molecule rather than the ribosome (Lu, 2013). Gamma-glutamyl transpeptidase cleaves the gamma bond (Hanigan, 2014). The cysteine-glycine bond is an ordinary peptide bond.
What is L-glutathione?
L-glutathione is the form found in nature. It is built from L-glutamate, L-cysteine and glycine. "Reduced L-glutathione" means GSH, the free thiol, rather than the disulfide GSSG. PubChem's systematic name labels the cysteine carbon (2R). This is still L-cysteine. The sulfur atom changes which group has priority. Commercial glutathione is usually made by fermentation (Santos et al., 2022).
What does "gluta peptide" mean?
Many listings use "gluta" as a short name for glutathione. So "gluta peptides" usually means glutathione itself. It is not glutamine or glutamic acid. These are single amino acids.
How should glutathione powder be stored?
Keep the lyophilized powder at -20°C and protected from light. After reconstitution, store the solution at 2 to 8°C and protected from light. Avoid freeze/thaw cycles. These conditions are listed on the product page.
Where can researchers buy glutathione?
Disguised Alpha sells it for laboratory research as a lyophilized powder, L-Glutathione, and as a 200 mg/mL solution, with certificates published by lot on each product page.
Related compounds and guides
- High Dose L-Glutathione (200MG/ML): the solution format
- TUDCA / S-Acetyl Glutathione
- SS-31 research guide
- MOTS-c research guide
- GHK-Cu research guide: another tripeptide
- KPV research guide: another tripeptide
- Peptide stability and storage guide
- COA portal: published certificates for each lot
This product is for research use only. It has not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.