Glutathione (GSH, gamma-glutamyl-cysteinyl-glycine) is the most abundant intracellular antioxidant in mammalian cells — present at 1-10 mM intracellular concentrations. Its thiol group (from cysteine) directly scavenges reactive oxygen species and serves as the substrate for the glutathione peroxidase (GPx) enzyme family — the primary cellular defence against lipid peroxidation and H2O2. GSH is also the co-factor for glutathione S-transferases (GSTs) in Phase II xenobiotic detoxification. Intracellular GSH depletion is a hallmark of oxidative stress, neurotoxicity, and ageing. QSC supplies glutathione as a research-grade compound for in vitro redox biology, oxidative stress modelling, and neurotoxicity protection research.
307.3 g/mol
MW — gamma-Glu-Cys-Gly
~5 mM
Intracellular GSH
GPx substrate
Glutathione peroxidase
Phase II
Detoxification substrate
≥99%
Purity
Glutathione — Specifications
Property
Value
CAS
70-18-8
Formula
C10H17N3O6S
MW
307.3 g/mol
Half-life
Short plasma; intracellular reservoir replenished
Class
Tripeptide antioxidant — gamma-Glu-Cys-Gly
Purity
≥99% HPLC verified
COA
Janoshik independent third-party
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Mechanism of Action — Glutathione
Glutathione operates as the central redox buffer through three primary mechanisms:
Direct ROS scavenging: GSH thiol directly reduces superoxide, H2O2, and hydroxyl radicals → GSSG (oxidised glutathione). GSSG is recycled to GSH by glutathione reductase (GR) using NADPH
GPx substrate: Glutathione peroxidase (GPx1-8) uses GSH to reduce H2O2 and lipid hydroperoxides → H2O + GSSG. Primary pathway for H2O2 and lipid peroxidation defence
GST conjugation: Glutathione S-transferases conjugate GSH to electrophilic xenobiotics → mercapturic acid excretion. Phase II detoxification pathway
Protein S-glutathionylation: Under oxidative stress, protein cysteines form mixed disulphides with GSH (reversible) — protective modification preventing irreversible oxidation
GSH depletion as an experimental tool
Buthionine sulfoximine (BSO) inhibits gamma-glutamylcysteine synthetase — depleting intracellular GSH to less than 10% baseline within 24hr. BSO + glutathione repletion is the standard experimental pair for studying whether an observed oxidative stress phenotype is GSH-dependent. NAC is the clinical GSH precursor; exogenous GSH is the direct repletion tool in cell culture.
Key Research Studies & Data
Study
Model
Finding
Ballatori et al. 2009 (Biol Chem review)
GSH biology overview
GSH as central redox buffer, GPx/GR/GST axis — foundational review
Dringen et al. 2005 (J Neurochem)
Neuronal GSH depletion
GSH required for neuronal survival; depletion with BSO causes oxidative neurodegeneration
Townsend et al. 2003 (Oncogene)
Cancer chemoresistance
Elevated GSH in cancer cells confers resistance to cisplatin and doxorubicin — GSH depletion sensitises tumour cells
Research Protocols — Glutathione
Protocol 1: Oxidative stress GSH depletion model
BSO 1 mM in SH-SY5Y or primary neurons × 24hr. Then GSH 1-5 mM or NAC 5 mM repletion × 24hr. Outcomes: cell viability (MTT/LDH), intracellular GSH (Ellman reagent), ROS (DCFH-DA), lipid peroxidation (MDA/TBARS), protein carbonylation, mitochondrial membrane potential (JC-1).
Protocol 2: Neuroprotection (H2O2/MPP+ model)
GSH 1-10 mM in primary cortical neurons 1hr pre-treatment → H2O2 200 µM or MPP+ 500 µM 24hr. Viability (LDH/MTT), caspase-3 activity, 8-OHdG (DNA oxidation), MDA. Mitochondrial protection: Seahorse respiration.
GSH measurement in tissue panels from young (3mo) vs middle (12mo) vs old (24mo) C57BL/6 mice. Brain, liver, kidney, plasma (Ellman reagent). Correlate with oxidative stress biomarkers (MDA, protein carbonyl, 8-OHdG) and GSH synthesis enzyme expression.
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Frequently Asked Questions
What is glutathione?
Glutathione (GSH) is the primary intracellular antioxidant — a tripeptide (gamma-Glu-Cys-Gly) present at 1-10 mM in cells. It scavenges ROS directly, serves as the substrate for glutathione peroxidase (H2O2 defence), and enables Phase II xenobiotic detoxification via glutathione S-transferases.
How does the glutathione redox cycle work?
GSH is oxidised to GSSG when reducing H2O2 or other oxidants. GSSG is recycled back to GSH by glutathione reductase (GR) using NADPH as cofactor. Maintaining a high GSH/GSSG ratio (normally over 100:1) is essential for cellular redox homeostasis.
Why does glutathione decline with age?
Intracellular GSH synthesis declines with age due to reduced expression of gamma-glutamylcysteine ligase (GCL) subunits, reduced NADPH availability (linked to NAD+ decline), and increased oxidative burden. GSH depletion correlates with age-related neurodegeneration.
Can exogenous glutathione enter cells?
Exogenous GSH is rapidly degraded by gamma-glutamyl transpeptidase on cell surfaces — making direct supplementation less effective than precursors (NAC, glycine, cysteine) in vivo. In cell culture, direct GSH addition is effective when GGT activity is low or absent.
What formats does QSC supply glutathione in?
QSC supplies glutathione as lyophilised research powder in research kits, ≥99% purity HPLC verified with Janoshik COA. Ships from domestic warehouses in USA, EU, UK, Canada, and Australia.
