Glutathione

Glutathione is a tripeptide (γ-Glu-Cys-Gly) found in nearly all cells, where it acts as a major antioxidant and redox buffer. Its glutamate is linked through the side-chain gamma carboxyl, an unusual, non-standard peptide bond.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Glutathione is the most abundant low-molecular-weight thiol in animal cells and is also found in plants, fungi and many bacteria. It is synthesized inside cells in two enzymatic steps rather than on the ribosome: glutamate-cysteine ligase joins glutamate and cysteine, and glutathione synthetase adds glycine. Its reactive cysteine thiol allows it to neutralize reactive oxygen species, maintain proteins in a reduced state and participate in detoxification reactions.

Glutathione exists mainly in a reduced form (GSH) and an oxidized, disulfide-linked dimer (GSSG). The ratio of the two is used as an indicator of cellular redox status. Glutathione has been studied extensively in biochemistry and in clinical research, including trials of oral and other forms of supplementation, with variable results on whether tissue levels change. It is not approved by the FDA as a drug for any specific condition.

Structure

Glutathione is a tripeptide composed of glutamate, cysteine and glycine. Unusually, the glutamate is linked to cysteine through its side-chain gamma carboxyl group rather than its alpha carboxyl, forming a γ-glutamyl bond that resists most peptidases; this is why it is written γ-Glu-Cys-Gly. The cysteine thiol is the reactive center. The oxidized form, GSSG, consists of two glutathione molecules joined by a disulfide bond. Glutathione can also form mixed disulfides with protein cysteines.

Mechanism

Glutathione's main roles derive from its cysteine thiol. It directly reduces reactive oxygen species and serves as the electron donor for glutathione peroxidases, which reduce hydrogen peroxide and lipid peroxides; GSSG formed in these reactions is recycled to GSH by glutathione reductase using NADPH. Glutathione S-transferases conjugate glutathione to electrophilic compounds, a key step in detoxification of drugs and toxins. It also participates in protein glutathionylation, a reversible modification involved in redox signaling. The γ-glutamyl cycle, involving γ-glutamyl transferase, handles its extracellular breakdown and the recovery of its amino acids.

Research

Redox biology and oxidative stress

Glutathione is central to research on oxidative stress, and the GSH/GSSG ratio is a widely used measure of cellular redox state. Depletion of glutathione has been documented in many cell and animal models of injury and in observational studies of various human conditions. Such associations do not by themselves show that raising glutathione is beneficial. Measurement of GSH and GSSG is technically demanding because samples oxidize during handling.

Detoxification and drug metabolism

Glutathione conjugation is a major pathway for metabolizing reactive compounds. A well-characterized example is acetaminophen overdose, where depletion of hepatic glutathione allows a toxic metabolite to accumulate; the approved antidote, N-acetylcysteine, works partly by supplying cysteine for glutathione synthesis. This mechanism is well established in pharmacology. Genetic variation in glutathione S-transferase enzymes is also studied for its effects on drug metabolism and susceptibility to environmental toxins. These pathways are well characterized in human pharmacology.

Supplementation studies

Clinical studies have examined whether oral, liposomal or other forms of glutathione raise blood or tissue levels. Results have varied: some trials reported increases in body stores after sustained oral intake, while others found little change, reflecting breakdown in the gut and limited uptake. Effects on clinical outcomes have not been established in large trials. Formulation and study duration vary widely between trials.

Precursor approaches

Because glutathione itself is poorly absorbed intact, researchers have also studied precursors such as N-acetylcysteine and glycine, alone or combined, as ways to support glutathione synthesis. Small human studies have reported changes in glutathione levels and related markers, but larger outcome trials are limited. Interpretation is complicated because N-acetylcysteine and glycine have biological effects of their own beyond supplying glutathione building blocks. Outcome data from adequately powered trials are limited.

Regulatory status

Glutathione is not FDA-approved as a drug for any specific indication. In the United States it is sold as a dietary supplement ingredient, and its status in compounding should be checked against current FDA lists, which can change. Regulatory treatment differs in other countries; check local status. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A glutathione certificate of analysis should confirm identity, ideally by mass spectrometry against the expected mass, and report purity by HPLC. The key quality issue is oxidation: the certificate should quantify reduced glutathione and the oxidized dimer GSSG separately, since GSH converts to GSSG on exposure to air and moisture. Other relevant impurities include cysteinylglycine, γ-glutamylcysteine and related degradation products. The material should be identified as reduced (GSH) or oxidized (GSSG) glutathione, and water content and heavy metals are commonly reported.

Open Glutathione in the sequence analyzer to see the expected [M+H]⁺ and multiply charged ions for an MS identity check.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store glutathione powder tightly sealed, protected from moisture, light and air, at -20 °C for long-term research storage. Reduced glutathione oxidizes readily in solution, especially at neutral to basic pH and in the presence of trace metals, so prepare solutions fresh, use degassed buffers where oxidation matters, and consider a metal chelator in the buffer. Do not store reduced solutions for long periods.

Download the Glutathione data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• NAD+

  NAD+ (nicotinamide adenine dinucleotide) is not a peptide; it is a dinucleotide coenzyme essential for redox metabolism and a substrate for sirtuins, PARPs and CD38. It is studied in aging and metabolic research.

• SS-31 (elamipretide)

  SS-31, known as elamipretide, is a synthetic mitochondria-targeted tetrapeptide that binds the inner-membrane lipid cardiolipin. It received FDA accelerated approval in September 2025 as Forzinity for Barth syndrome.

• 5-Amino-1MQ

  5-Amino-1MQ is not a peptide; it is a small-molecule quaternary quinolinium compound that inhibits the enzyme nicotinamide N-methyltransferase (NNMT). It has been studied in cell and rodent models of obesity and metabolism.

References

1. PubMed: all indexed literature on Glutathione
2. ClinicalTrials.gov: registered studies mentioning Glutathione