L-Glutathione (1500mg)

What is L-Glutathione?

L-Glutathione (GSH) is a tripeptide composed of glutamine, cysteine, and glycine. It occurs naturally in most eukaryotic cells and plays a central role in cellular redox balance, detoxification, and immune system regulation.

In research settings, it is widely studied for its role in protecting cells from oxidative damage, recycling antioxidants such as vitamin C and E, and influencing inflammatory and apoptotic signaling pathways.

L-Glutathione is available in both reduced (GSH) and oxidized (GSSG) forms, with the reduced form being the most biologically active. Evolve Peptides offers the reduced L-Glutathione form for advanced laboratory applications.

L-Glutathione has research applications in three key areas:

• Oxidative Stress Modulation: GSH acts as a major intracellular antioxidant, scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS).
• Detoxification Studies: Serves as a substrate for glutathione S-transferases (GSTs) in xenobiotic metabolism.
• Cell Health & Apoptosis Research: Regulates signaling related to cell proliferation, differentiation, and death.

L-Glutathione is highly soluble in water and exhibits good stability under refrigerated or ambient lab storage conditions when stored appropriately. Its well-characterized biochemical profile makes it a reliable tool in molecular biology, biochemistry, and pharmacology labs.

L-Glutathione Mechanism of Action (Based on Research)

L‑Glutathione (GSH) plays a central role in cellular redox regulation, detoxification, and signal transduction. Its mechanisms in research models can be broadly classified into antioxidant defense, detoxification of harmful metabolites, and redox signaling control.

1. Antioxidant Defense via Enzymatic Reduction of Peroxides

Glutathione serves as a co-substrate for glutathione peroxidase enzymes (GPx1–GPx4), catalyzing the reduction of hydrogen peroxide (H₂O₂) and organic peroxides into water and corresponding alcohols.

During this process, GSH is oxidized to glutathione disulfide (GSSG), which is then converted back to GSH by glutathione reductase using NADPH as a cofactor.

A 2020 review reports that 98% of glutathione in cells exists in the reduced (GSH) form, and that GPx, together with glutaredoxin systems, plays a central role in maintaining this redox balance by reducing peroxides and disulfide.

In vitro enzyme studies—including one with selenoglutathione—demonstrated that NADPH and glutathione reductase can reduce over 80% of 0.1 mM H₂O₂ via a GPx-like mechanism within minutes, highlighting the rapid scavenging ability of the GSH–GPx system [1].

This balanced enzymatic relay—GPx using GSH to neutralize peroxides, GSSG being recycled by glutathione reductase using NADPH—is the cornerstone of cellular antioxidant defense and redox regulation.

2. Non‑Enzymatic Detoxification and Thiol Protection

Glutathione (GSH) plays a crucial role not only in enzymatic antioxidant defense but also in direct, non‑enzymatic detoxification of reactive molecules and in safeguarding protein thiols. This phase of antioxidant activity encompasses several key mechanisms:

Direct Scavenging of Reactive Oxygen and Nitrogen Species

GSH can neutralize highly reactive species like hydroxyl radicals (•OH) and peroxynitrite (ONOO⁻), as well as lipid peroxidation byproducts such as malondialdehyde (MDA) and 4‑hydroxynonenal (4‑HNE) [2].

These latter compounds form when membrane lipids undergo oxidative damage by ROS and RNS—processes commonly observed in inflammation and cellular stress. By reacting directly with these aldehydes, GSH reduces their reactivity and prevents further cellular damage [3].

S‑Glutathionylation: Reversible Protection of Protein Thiols

Under oxidative stress, critical cysteine residues in proteins may undergo irreversible oxidation, impairing function. GSH protects against this through the formation of protein‑SS‑glutathione mixed disulfides, a process known as S‑glutathionylation.

This reversible modification both shields the thiol from permanent damage and serves as a regulatory redox “switch” in signaling pathways. It maintains protein thiol integrity and helps regulate enzymatic activity in response to changing redox conditions [4].

3. Maintenance of Redox Signaling and Cellular Homeostasis

Glutathione (GSH) plays a central role in maintaining the cellular redox environment, with the GSH:GSSG ratio—usually above 100:1 in healthy cells—serving as a key indicator of redox balance and oxidative stress [2]. This highly reduced state allows GSH to act as both a buffer and a signal mediator.

Reversible Thiol Modifications and Enzymatic Control

GSH engages in S‑glutathionylation, a reversible post-translational modification where a glutathionyl moiety forms mixed disulfides with protein cysteines.

This modification—catalyzed by enzymatic systems such as glutaredoxins—serves dual purposes of protection (prevents irreversible oxidation of sensitive thiol residues) and regulation (as a redox-controlled “switch” in proteins governing cell cycle, apoptosis, immune responses, and gene expression).

Biosynthesis and Regeneration Pathways of Glutathione

Glutathione (GSH) is synthesized in a highly conserved, two-step, ATP-dependent enzymatic process that ensures a steady supply of this critical antioxidant.

Step #1

Glutamate–Cysteine Ligase (GCL) catalyzes the condensation of L‑glutamate and L‑cysteine into γ‑glutamylcysteine. This is the rate-limiting step in GSH synthesis and is carried out by a heterodimer comprised of catalytic (GCLC) and modifier (GCLM) subunits. Genetic knockout of GCL subunits is lethal in mice, underscoring its essential biological role [5].

Step #2

Glutathione Synthase (GS) then adds glycine to γ‑glutamylcysteine, forming the tripeptide GSH. This step also consumes ATP and completes the biosynthetic pathway [6]. Together, these reactions require two ATP molecules per GSH molecule, sustaining millimolar concentrations of reduced glutathione in most cells.

Following oxidation—usually during peroxide detoxification—GSH is converted into glutathione disulfide (GSSG). Glutathione reductase (GSR), using NADPH as a cofactor, reduces GSSG back into two GSH molecules, thereby maintaining the cellular redox balance and allowing for continuous antioxidant activity [1].

L-Glutathione Research Applications

L‑Glutathione is among the most widely studied intracellular antioxidants, with diverse roles in redox regulation, detoxification, and cellular protection. Its applications in preclinical and biochemical research span multiple systems and disease models.

These are the most prominent areas.

Oxidative Stress and Antioxidant Pathways

Glutathione is central to research exploring how cells defend against oxidative stress. In both in vitro and animal models, GSH depletion correlates strongly with increased oxidative damage, mitochondrial dysfunction, and apoptosis [7].

Supplementing or preserving GSH levels has been shown to: 

• Limit lipid peroxidation and DNA damage in oxidative stress models [8]
• Protect neurons in models of Parkinson’s and Alzheimer’s disease by reducing ROS levels
• Improve mitochondrial function and membrane stability

These findings make GSH essential in studies targeting aging, neurodegeneration, cardiovascular disease, and metabolic syndrome.

Detoxification and Hepatic Function Models

L‑Glutathione is extensively studied for its role in hepatic detoxification, particularly in research related to liver injury and xenobiotic metabolism [9]. In hepatocyte cultures and animal studies:

• GSH conjugation aids in metabolizing drugs, alcohol byproducts, and pollutants [10]
• Depletion of GSH enhances liver sensitivity to toxins like acetaminophen or aflatoxin
• GSH status is used as a biomarker of hepatic health and recovery potential

Thus, L-glutathione is valuable in toxicology and pharmacokinetic research.

Redox Regulation of Immune Function

Glutathione is a redox buffer in immune cells. Research has shown that low intracellular GSH levels impair lymphocyte activation and cytokine production.

Similarly, GSH modulates T-cell proliferation and helps prevent excessive inflammatory signaling. GSH also participates in antigen presentation and phagocytic function of macrophages.

These properties make it relevant in research on chronic inflammation, immune exhaustion, and autoimmune conditions.

Neuroprotection and Brain Health

Because neurons are highly susceptible to oxidative stress, GSH is a focus in neurological research. In vitro studies show that raising GSH levels reduces ROS-induced neurotoxicity.

In animal models, GSH depletion is linked to early neurodegeneration and cognitive decline. Thus, it may influence glutamate cycling and neurotransmitter balance indirectly.

Glutathione is frequently used as a benchmark compound in testing neuroprotective agents or antioxidants.

Cellular Aging and Longevity Research

L‑Glutathione is also explored in the context of aging due to its role in:

• Limiting mitochondrial damage over time
• Preserving DNA integrity by minimizing oxidative mutations
• Supporting proteostasis and redox-sensitive signaling cascades

Studies on caloric restriction and lifespan extension often measure or manipulate GSH levels as part of the cellular stress response pathway.

L-Glutathione Characteristics

• Chemical Name: L‑Glutathione (Reduced form)
• CAS Number: 70‑18‑8
• Molecular Formula: C₁₀H₁₇N₃O₆S
• Molecular Weight: ~307.32 g/mol
• Synonyms: GSH, γ‑L‑Glutamyl‑L‑cysteinylglycine, Reduced Glutathione
• Peptide Sequence: γ‑Glu‑Cys‑Gly (gamma‑Glutamylcysteinylglycine)
• Appearance: White to off-white crystalline powder
• Solubility: Highly soluble in water; slightly soluble in alcohol
• Purity: ≥99% (HPLC-verified; third-party tested)
• Storage recommendations:
  • Store the lyophilized form at −20°C to −10°C (−4°F to 14°F) in a cool, dry, dark environment.
  • Once reconstituted, store at 2°C to 8°C (36°F to 46°F) and use within a short time frame appropriate to your lab’s protocol.
  • Avoid repeated freeze-thaw cycles to preserve stability and structure.

Glutathione vs NAC vs Alpha-Lipoic Acid Comparison

L-Glutathione Safety & Stability

However, oxidation is a genuine concern: GSH degrades rapidly at room temperature in solution and should be stored cold in dry, oxygen-limited conditions for optimal stability.

Specifically, 200 µM solutions held at 25 °C showed a 15% loss, while those at 50 °C lost up to 67% within an hour [12]. Long-term stability is manageable when refrigerated: GSH solutions stored at 4–5 °C retained over 90% integrity for several weeks.

Legal Disclaimer

L-glutathione is intended strictly for laboratory research purposes only. It is not approved for human or veterinary use, and must not be used for diagnostic, therapeutic, or clinical applications.

By purchasing from Evolve Peptides, you acknowledge that you are a qualified researcher or acting under the supervision of a licensed professional. It is the customer’s responsibility to ensure proper handling, storage, and disposal in accordance with applicable laws and institutional protocols.

Certificate of Analysis (COA)

Each batch of L‑Glutathione is subjected to third-party testing to confirm identity, purity (≥99%), and quality specifications.

COAs are made available with every product shipment and can be requested directly by contacting Evolve Peptides. These include:

• Mass spectrometry and HPLC results
• Purity confirmation (≥99%)
• Batch number and production date

For sample documentation or specific lot information, please reach out to the friendly and highly experienced Evolve Peptides support team via our contact page.

Scientific References

1. 1.Vašková, J., Kočan, L., Vaško, L., & Perjési, P. (2023). Glutathione-Related Enzymes and Proteins: A Review. Molecules, 28(3), 1447. https://www.mdpi.com/1420-3049/28/3/1447 
2. Vašková, J., Kočan, L., Vaško, L., & Perjési, P. (2023). Glutathione-Related Enzymes and Proteins: A Review. Molecules, 28(3), 1447. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00196/full
3. Lushchak, Volodymyr I., Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions, Journal of Amino Acids, 2012, 736837, 26 pages, 2012. https://onlinelibrary.wiley.com/doi/10.1155/2012/736837
4. Vašková, J., Kočan, L., Vaško, L., & Perjési, P. (2023). Glutathione-Related Enzymes and Proteins: A Review. Molecules, 28(3), 1447. https://www.mdpi.com/1420-3049/28/3/1447
5. Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013 May;1830(5):3143-53. doi: 10.1016/j.bbagen.2012.09.008. Epub 2012 Sep 17. PMID: 22995213; PMCID: PMC3549305. https://pmc.ncbi.nlm.nih.gov/articles/PMC3549305/
6. Maughan, S. and Foyer, C.H. (2006), Engineering and genetic approaches to modulating the glutathione network in plants. Physiologia Plantarum, 126: 382-397. https://onlinelibrary.wiley.com/doi/10.1111/j.1399-3054.2006.00684.x
7. Marí M, Morales A, Colell A, García-Ruiz C, Fernández-Checa JC. Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal. 2009 Nov;11(11):2685-700. doi: 10.1089/ARS.2009.2695. PMID: 19558212; PMCID: PMC2821140. https://pmc.ncbi.nlm.nih.gov/articles/PMC2821140/
8. Jasvinder Singh Bhatti, Gurjit Kaur Bhatti, P. Hemachandra Reddy, Mitochondrial dysfunction and oxidative stress in metabolic disorders — A step towards mitochondria based therapeutic strategies, Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, Volume 1863, Issue 5, 2017, Pages 1066-1077, ISSN 0925-4439 https://www.sciencedirect.com/science/article/pii/S0925443916302927 
9. Chen, T.-H., Wang, H.-C., Chang, C.-J., & Lee, S.-Y. (2024). Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation. International Journal of Molecular Sciences, 25(2), 1314.https://www.mdpi.com/1422-0067/25/2/1314
10. Ribas, V., García‑Ruiz, C., & Fernández‑Checa, J. C. (2014). Glutathione and mitochondria. Frontiers in Pharmacology, 5, Article 151. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00151/full
11. Campbell KC, Larsen DL, Meech RP, Rybak LP, Hughes LF. Glutathione ester but not glutathione protects against cisplatin-induced ototoxicity in a rat model. J Am Acad Audiol. 2003 Apr;14(3):124-33. PMID: 12859137. https://pubmed.ncbi.nlm.nih.gov/12859137/
12. Nuhu F, Gordon A, Sturmey R, Seymour AM, Bhandari S. Measurement of Glutathione as a Tool for Oxidative Stress Studies by High Performance Liquid Chromatography. Molecules. 2020 Sep 13;25(18):4196. doi: 10.3390/molecules25184196. PMID: 32933160; PMCID: PMC7571047. https://pmc.ncbi.nlm.nih.gov/articles/PMC7571047/