Glutathione

Glutathione is a tripeptide of glutamate, cysteine and glycine in which the glutamate is joined through its side-chain carboxyl, and it is found in every mammalian tissue. This listing is a sealed vial holding 1500 mg of the reduced form, GSH, as a dry white solid. Research on glutathione covers how cells build and break it down, its place as the main non-protein thiol in redox balance, and a smaller set of human studies comparing ways of delivering it.

Handling notes

The cysteine in glutathione carries a free thiol. That group is what makes GSH a reducing agent, and it is also the part that oxidises: two molecules joined by a disulfide bond form glutathione disulfide, GSSG, a dimer of about 612.6 Da. A sample that has been exposed to air, moisture or long periods in solution can therefore hold a mixture of the two forms. The storage line on the lot certificate follows from this: −20 °C, desiccated, dark and protected from air. Keep the vial closed except while weighing, and return it to the freezer promptly.

The certificate reports the LC-MS identity result for the reduced free acid, to compare with the theoretical mass of 307.3 Da. At that mass, 1500 mg is about 4.9 mmol of glutathione, slightly less once the residual water on the certificate is allowed for. General guidance on keeping peptides cold, dry and dark is in the peptide storage and stability article.

What the research covers

What glutathione does in cells

Glutathione is present in all mammalian tissues and is the most abundant thiol that is not part of a protein¹. In a 2013 review, Lu described it as a defence against oxidative stress and a determinant of redox signalling, needed for the detoxification of foreign compounds and involved in regulating cell proliferation, apoptosis, immune function and fibrogenesis¹. Cells make it in the cytosol in two enzymatic steps. The first and rate-limiting step is catalysed by glutamate cysteine ligase, an enzyme with a catalytic and a modifier subunit, and glutathione synthetase completes the molecule¹. How fast synthesis runs depends mainly on the supply of cysteine, the sulfur amino acid precursor, and on the ligase's activity¹. Both enzymes are regulated at several levels, often together, and the transcription factors involved include Nrf2 acting through the antioxidant response element, AP-1 and NF-κB¹. Lu linked faulty glutathione synthesis to diabetes, to pulmonary and liver fibrosis and to alcoholic liver disease, among other conditions¹.

Breakdown and transport

Glutathione was discovered in 1888, and since 1970 its metabolism has mostly been drawn as the γ-glutamyl cycle². Bachhawat and Yadav argued in 2018 that newer work on how glutathione is transported and degraded shows many parts of that cycle to be wrong, and they proposed a revised glutathione cycle in its place². The gamma linkage is central to that story. Because glutamate is attached to cysteine through its side-chain carboxyl, ordinary peptidases do not cleave the bond, and breakdown depends on enzymes that recognise it: γ-glutamyl transpeptidase outside the cell and the ChaC enzymes inside it, as the glutathione guide explains.

Routes of delivery

The references on this page contain no human study of glutathione given by any route. The glutathione routes guide covers that literature: two intravenous pharmacokinetic studies found a plasma half-life of about fourteen minutes, oral glutathione raised blood levels measurably only after months, and the intranasal work comes almost entirely from one research group. For the nasal route in general, Illum's 2002 review discussed evidence that some drugs pass from the nose to the brain along the olfactory pathway, with proof-of-concept examples in humans³. That review did not study glutathione.glutathione 250 mg nasal spray.

What is not established

Cells already hold glutathione at millimolar concentrations, so adding more to a culture or tissue changes a pool that is large to begin with, and the guide notes that plasma levels are far lower, in the micromolar range. The cited reviews describe synthesis and turnover.

Frequently asked questions

References

1. Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013;1830(5):3143-53. DOI · PubMed
2. Bachhawat AK, Yadav S. The glutathione cycle: Glutathione metabolism beyond the γ-glutamyl cycle. IUBMB Life. 2018;70(7):585-592. DOI · PubMed
3. Illum L. Nasal drug delivery: new developments and strategies. Drug Discov Today. 2002;7(23):1184-9. DOI · PubMed