Biosynthesis and its regulation
Reviews have examined the two-step synthesis of GSH, the regulation of glutamate cysteine ligase and GSH synthetase at multiple levels, and conditions in which synthesis is dysregulated in experimental models1,3.
Research Peptide · For laboratory research use only
Glutathione
Also known as GSH, L-Glutathione
- Formula
- C10H17N3O6S
- CAS
- 70-18-8
Available as
Overview
Glutathione (GSH, gamma-L-glutamyl-L-cysteinylglycine) is a tripeptide synthesised in the cytosol of animal cells and is the most abundant low-molecular-weight thiol; the GSH/glutathione disulfide pair is the major redox couple in animal cells1,2.
Because it is an endogenous metabolite, the literature is large and largely biochemical. Reviews cover its synthesis and regulation, its role in antioxidant defence and conjugation of electrophiles, methods for measuring cellular GSH status, and more recent work on redox signalling1,2,3,4.
Mechanism of action
As described in the research literature
As described in the research literature, GSH is synthesised from glutamate, cysteine and glycine by two sequential cytosolic enzymes, glutamate cysteine ligase (also gamma-glutamylcysteine synthetase) and GSH synthetase. Synthesis is regulated mainly by glutamate cysteine ligase activity, cysteine availability and feedback inhibition by GSH1,3. Expression of the ligase subunits and GSH synthetase is controlled by transcription factors including Nrf2 acting through the antioxidant response element, AP-1 and NF-kappaB3.
GSH eliminates oxidants by reduction and electrophiles by conjugation, and maintains cellular redox homeostasis2. Reviews also describe roles in nutrient metabolism, gene expression, DNA and protein synthesis, signal transduction, cell proliferation and apoptosis, and protein glutathionylation, along with more recent work on nitroxidative stress and autophagy1,4.
Research areas
What published studies have examined
Experimental depletion of glutathione
Buthionine sulfoximine was characterised as a potent and specific inhibitor of gamma-glutamylcysteine synthetase, lowering kidney GSH in mice without detectable inhibition of glutamine synthetase. It was proposed as a tool for inhibiting GSH synthesis in experimental systems5.
Sources [5]
Oxidative stress and redox signalling
Reviews cover the sources of oxidants and electrophiles, methods for assessing GSH status in cells, and the role of GSH in redox signalling, including modulation of nitroxidative stress, autophagy and viral infection in cellular models2,4.
Specifications
- Structure
- gamma-L-Glutamyl-L-cysteinylglycine (reduced glutathione, GSH)
- Molecular formula
- C10H17N3O6S
- Molecular weight
- 307.3 g/mol
- CAS number
- 70-18-8
- Form
- White crystalline powder in a sealed vial (1500 mg)
- Storage
- Store lyophilised powder at -20 °C, protected from light and moisture. Once reconstituted, keep refrigerated at 2 to 8 °C and protect from light.
- Solubility and reconstitution
- Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and swirl gently until clear; do not shake.
References
- 1
Glutathione metabolism and its implications for health.
Wu G, Fang YZ, Yang S, et al. The Journal of Nutrition, 2004.
- 2
Glutathione: overview of its protective roles, measurement, and biosynthesis.
Forman HJ, Zhang H, Rinna A Molecular Aspects of Medicine, 2009.
- 3
Glutathione synthesis.
Lu SC Biochimica et Biophysica Acta, 2013.
- 4
Glutathione: new roles in redox signaling for an old antioxidant.
Aquilano K, Baldelli S, Ciriolo MR Frontiers in Pharmacology, 2014.
- 5
Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine).
Griffith OW, Meister A The Journal of Biological Chemistry, 1979.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.