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Glutathione

Glutathione (GSH) is a tripeptide composed of three amino acids—L-glutamate, L-cysteine, and glycine—linked by a unique γ-peptide bond between the side-chain carboxyl group of glutamate and the amino group of cysteine, with glycine attached to the carboxyl group of cysteine.^[1] As the most abundant low-molecular-weight thiol in most cells, it exists primarily in its reduced form (GSH) and plays essential roles in maintaining cellular redox balance, protecting against oxidative stress from reactive oxygen species (ROS) and reactive nitrogen species (RNS), and detoxifying xenobiotics and endogenous electrophiles.^[1]^[2] Glutathione is synthesized in the cytosol through two sequential ATP-dependent enzymatic reactions: the first, catalyzed by γ-glutamylcysteine ligase (also known as glutamate-cysteine ligase), forms γ-glutamylcysteine from glutamate and cysteine; the second, mediated by glutathione synthetase, adds glycine to produce GSH.^[1] Intracellular concentrations of GSH typically range from 1 to 10 mM, with particularly high levels in hepatocytes (up to 10 mM) and in extracellular fluids like lung epithelial lining fluid, where it contributes to defense against inhaled oxidants.^[1]^[2] Homeostasis is tightly regulated by biosynthesis, utilization in conjugation or oxidation to GSSG (glutathione disulfide), recycling via glutathione reductase using NADPH, and transport across membranes, ensuring a predominantly reduced state with a redox potential of approximately -260 to -150 mV.^[2] In its antioxidant capacity, GSH directly neutralizes ROS such as hydroxyl radicals (HO•) and peroxynitrite (ONOO⁻), or acts as a cofactor for enzymes like glutathione peroxidases (GPx), which reduce peroxides including hydrogen peroxide (H₂O₂), and glutathione S-transferases (GST), which conjugate electrophiles for excretion.^[1]^[2] Beyond redox protection, GSH serves as a reservoir for cysteine, facilitates the metabolism of compounds like estrogens and leukotrienes, supports ribonucleotide reduction for DNA synthesis, aids in iron-sulfur cluster maturation, and regulates protein function through S-glutathionylation and S-nitrosation.^[2] Its depletion is associated with oxidative stress-related pathologies, including neurodegenerative diseases (e.g., Parkinson's and Alzheimer's), cancer, diabetes, cardiovascular disorders, and liver diseases, underscoring its evolutionary conservation across organisms and potential as a therapeutic target via precursors like N-acetylcysteine.^[2]

Chemical Structure and Properties

Molecular Composition

Glutathione, commonly abbreviated as GSH, is a tripeptide molecule consisting of three amino acids: L-glutamic acid, L-cysteine, and glycine, linked in the sequence γ-L-glutamyl-L-cysteinyl-glycine.^[3] The distinctive γ-carboxyl amide linkage forms between the side-chain carboxyl group of the glutamic acid residue and the amino group of the cysteine residue, setting it apart from conventional peptides that rely on α-carboxyl linkages for their bonds.^[4] This non-standard bonding contributes to its unique chemical behavior and resistance to typical peptidases.^[4] The molecular formula of glutathione is \ce{C10H17N3O6S}, with a molecular weight of 307.32 g/mol.^[3] It exhibits high solubility in water, approximately 292.5 mg/mL, attributable to its polar functional groups including the carboxylic acids, amide bonds, and amino groups.^[3] Under physiological conditions (pH around 7.4), glutathione maintains stability, with minimal degradation in aqueous environments over time in biological contexts.^[5] Structurally, the molecule features the glutamic acid residue at the N-terminus, connected via its γ-carboxyl to the cysteine, which in turn forms a standard peptide bond with the C-terminal glycine. The side chain of the cysteine bears a thiol (-SH) group, which serves as the primary reactive moiety. This thiol is pivotal for redox processes, enabling interconversion between reduced (GSH) and oxidized forms. In contrast to free cysteine or simpler thiols, glutathione's tripeptide configuration enhances the thiol's accessibility while providing greater overall stability against oxidation and enzymatic cleavage in cellular environments.^[6]^[3]

Redox States

Glutathione exists primarily in two redox states: the reduced form, known as glutathione (GSH), which is a monomeric tripeptide featuring a free thiol (-SH) group on its cysteine residue, and the oxidized form, glutathione disulfide (GSSG), which is a dimer formed by the oxidation of two GSH molecules linked through a disulfide (-S-S-) bond between their thiol groups.^[7]^[6] The interconversion between these states is fundamental to glutathione's role in redox homeostasis. The oxidation reaction is depicted as:

$2 \text{GSH} \rightarrow \text{GSSG} + 2 \text{H}^+ + 2 \text{e}^-

The reverse reduction process regenerates GSH from GSSG:

\text{GSSG} + 2 \text{H}^+ + 2 \text{e}^- \rightarrow 2 \text{GSH}

This reduction is enzymatically catalyzed by glutathione reductase, which utilizes NADPH as the cofactor to provide the necessary electrons.^[6]^[8] In healthy cells, the equilibrium ratio of GSH to GSSG is maintained at a high level, typically exceeding 100:1, which serves as a critical indicator of the intracellular redox environment; shifts toward a lower ratio signal oxidative stress.^[9]^[10] These redox states can be distinguished spectroscopically through their UV absorbance properties: GSH primarily absorbs at 210 nm, reflecting its peptide backbone, whereas GSSG displays an additional characteristic absorption at 250 nm due to the disulfide bond.^[11]^[12]

Biosynthesis and Catabolism

Biosynthesis Pathway

Glutathione (GSH) is synthesized de novo in the cytosol through a two-step, ATP-dependent enzymatic pathway that incorporates three amino acid precursors: L-glutamate, L-cysteine, and glycine.^[13] The first step involves the formation of γ-L-glutamyl-L-cysteine from L-glutamate and L-cysteine, catalyzed by the enzyme γ-glutamylcysteine synthetase (also known as glutamate-cysteine ligase, GCL).^[13] This reaction is the rate-limiting step in GSH biosynthesis and is subject to feedback inhibition by GSH itself, which helps regulate intracellular levels.^[14] In the second step, γ-L-glutamyl-L-cysteine is conjugated with glycine to form the tripeptide GSH, a process catalyzed by glutathione synthetase (GS).^[13] Each molecule of GSH produced requires the hydrolysis of two ATP molecules—one for each enzymatic step—highlighting the energy investment in this protective pathway.^[15] The resulting GSH molecule consists of a γ-glutamyl linkage between glutamate and cysteine, followed by a peptide bond to glycine, which contributes to its unique biochemical properties.^[16] Among the precursors, cysteine availability is the primary limiting factor for GSH synthesis, as it is the least abundant and must often be obtained from dietary sources or derived from methionine via the transsulfuration pathway in mammals.^[17] Inadequate cysteine supply can thus constrain overall GSH production, particularly under oxidative stress conditions that increase demand.^[18] The enzymes involved are encoded by conserved genes across eukaryotes and prokaryotes, reflecting the evolutionary importance of GSH homeostasis. GCL is a heterodimer composed of a catalytic subunit (GCLC) and a modifier subunit (GCLM), with GCLC providing the core activity and GCLM enhancing efficiency by reducing sensitivity to feedback inhibition.^[19] GS is encoded by the GSS gene. These genes show high sequence conservation, including key catalytic residues, from yeast and plants to mammals, underscoring the pathway's ancient origins likely acquired via endosymbiotic events.^[20]^[21]

Degradation Mechanisms

Glutathione degradation in mammalian cells primarily occurs through the γ-glutamyl cycle, a pathway that facilitates the breakdown and recycling of glutathione (GSH) and its oxidized form (GSSG) extracellularly, with subsequent intracellular processing of components. The cycle is initiated by γ-glutamyl transpeptidase (GGT), a membrane-bound ectoenzyme highly expressed on the apical surfaces of epithelial cells, particularly in the liver (bile canaliculi) and kidney (brush border). GGT cleaves the γ-glutamyl bond of extracellular GSH or GSSG, transferring the γ-glutamyl moiety to an acceptor amino acid or water to form γ-glutamyl-amino acid and cysteinylglycine (Cys-Gly).^[13]^[22] The dipeptide Cys-Gly is then hydrolyzed by extracellular or membrane-associated dipeptidases into free cysteine and glycine, which can be transported back into cells for GSH resynthesis.^[13] This extracellular degradation plays a crucial role in interorgan GSH homeostasis, as the liver continuously exports GSH and GSSG into plasma and bile to supply extrahepatic tissues like the kidney, lung, and intestine. In the kidney, high GGT activity enables the reabsorption and salvage of filtered GSH by breaking it down into amino acids, preventing urinary loss and supporting systemic cysteine availability.^[13]^[22] Intracellularly, the internalized γ-glutamyl-amino acid is further metabolized by γ-glutamyl cyclotransferase, which converts it to 5-oxoproline and the free amino acid; 5-oxoproline is then hydrolyzed by 5-oxoprolinase to glutamate, completing the recycling of constituent amino acids (glutamate, cysteine, glycine) for new GSH synthesis.^[13] Other intracellular peptidases may contribute to minor breakdown pathways, though the γ-glutamyl cycle dominates in mammals.^[22] The half-life of GSH in cells is typically 2–4 hours in the cytosol of rat hepatic cells, reflecting a dynamic balance between synthesis, export, and degradation that is accelerated under oxidative stress conditions, which increase GSH turnover to maintain redox homeostasis.^[22] Pathological disruptions, such as GGT deficiency—a rare autosomal recessive disorder caused by mutations in the GGT1 gene—impair this cycle, leading to extracellular GSH accumulation, glutathionuria (elevated urinary GSH), and elevated plasma GSH levels due to reduced breakdown and recycling efficiency.^[23] This results in limited cysteine availability for intracellular GSH synthesis, contributing to oxidative stress vulnerability despite overall GSH excess in some compartments.^[23]

Biological Distribution

In Animals and Humans

Glutathione is present ubiquitously in all eukaryotic cells of animals and humans, where it functions as the predominant low-molecular-weight thiol. Intracellular concentrations typically range from 1 to 10 mM across tissues, with the highest levels in the liver (5-10 mM), erythrocytes (2-3 mM), and the lens of the eye (4-6 mM). These elevated concentrations in specific tissues reflect glutathione's role in protecting against oxidative damage in metabolically active or vulnerable sites.^[24]^[25]^[26]^[27] Within animal and human cells, glutathione distribution is compartmentalized, with approximately 80-85% localized in the cytosol, 10-15% in the mitochondria, and the remainder in the nucleus and endoplasmic reticulum, enabling targeted redox regulation in these organelles. In contrast, extracellular fluids maintain substantially lower levels to support intercellular signaling and prevent excessive reduction potential. Human plasma concentrations of reduced glutathione (GSH) are typically 2-20 μM, while oxidized glutathione (GSSG) rises under stress; these are quantified via high-performance liquid chromatography (HPLC) or enzymatic recycling assays for precise assessment.^[28]^[2]^[29]^[30]^[31] Developmental profiles show higher fetal glutathione levels compared to adults, with a postnatal decline, particularly evident in preterm infants where rapid depletion occurs due to heightened oxidative stress at birth. Across species, concentrations vary, with rodents displaying higher levels than humans, linked to their elevated metabolic rates; for instance, rodent tumor cells exhibit significantly greater glutathione content relative to human equivalents.^[32]^[33]^[34]

In Plants and Microorganisms

In plants, glutathione is distributed throughout various tissues and organelles, with typical concentrations ranging from 100 to 500 μM in leaf cells.^[35] Chloroplasts often exhibit higher levels, between 0.5 and 5 mM, reflecting their role in photosynthetic redox balance, while vacuoles can accumulate glutathione at 0.08 to 0.7 mM, facilitating sequestration of oxidized forms and heavy metal complexes.^[35] This compartmentalization supports vacuolar storage as a detoxification mechanism, where glutathione conjugates are transported and stored to prevent cytosolic overload.^[36] In microorganisms, glutathione serves as an essential low-molecular-weight thiol, particularly in bacteria like Escherichia coli, where cytosolic concentrations reach 5 to 10 mM to maintain redox homeostasis.^[37] In yeast such as Saccharomyces cerevisiae, glutathione constitutes up to 3% of the cellular dry weight, aiding in oxidative stress defense during fermentation and growth.^[38] However, its presence varies among prokaryotes; while conserved across many bacteria, it is absent in certain anaerobes and replaced by alternatives like mycothiol in Actinobacteria, which performs analogous protective functions such as ROS scavenging and protein thiol protection.^[39] Evolutionarily, glutathione biosynthesis is highly conserved in eukaryotes, tracing back to cyanobacterial ancestors and retained through endosymbiotic events, but its distribution in prokaryotes is more variable, with losses in obligate anaerobes lacking oxidative stress pressures.^[40] In plants, glutathione levels are upregulated under environmental stresses, including heavy metal exposure (e.g., cadmium or arsenic) and pathogen attacks, where synthesis increases to bolster antioxidant capacity and xenobiotic conjugation.^[41] Quantification of glutathione in plant tissues often employs fluorescence-based assays, such as those using monochlorobimane (mBCl) derivatives, which form fluorescent adducts detectable in vivo via confocal microscopy, allowing non-destructive measurement of reduced glutathione in single cells or organelles like chloroplasts.^[42] These methods provide spatial resolution, revealing stress-induced gradients without disrupting cellular integrity.^[43]

Core Biochemical Functions

Antioxidant Activity

Glutathione (GSH) serves as a key antioxidant through both direct and indirect mechanisms to neutralize reactive oxygen species (ROS) and maintain cellular redox balance. In its reduced form, GSH directly scavenges highly reactive ROS such as hydroxyl radicals (•OH), with a second-order rate constant of 9 × 10⁹ M⁻¹ s⁻¹, forming the glutathione thiyl radical (GS•) and thereby preventing damage to cellular components.^[44] This non-enzymatic reaction is particularly effective against •OH, which arises from Fenton chemistry and can initiate destructive chain reactions in biomolecules. Additionally, GSH can reduce lipid peroxyl radicals directly, contributing to early-line defense against oxidative stress.^[45] Indirectly, GSH functions as a substrate for antioxidant enzymes, amplifying its protective capacity. Glutathione peroxidase (GPx) utilizes GSH to reduce hydrogen peroxide (H₂O₂) and organic hydroperoxides (ROOH), following the reaction:

$2\text{GSH} + \text{ROOH} \rightarrow \text{GSSG} + \text{H}_2\text{O} + \text{ROH}

where GSSG is the oxidized disulfide form of glutathione.^[45] This enzymatic process is essential since GSH does not react non-enzymatically with H₂O₂ at physiological rates. Glutaredoxins (Grxs), such as the cytosolic Grx1 and mitochondrial Grx2, further employ GSH to catalyze deglutathionylation of proteins, reversing oxidative modifications and restoring protein function during stress.^[45] These mechanisms collectively prevent oxidative damage to lipids (via inhibition of peroxidation), proteins (by limiting thiol oxidation), and DNA (by scavenging ROS that cause strand breaks).^[1] The GSH/GSSG ratio acts as a critical redox sensor, typically maintained at 10–100:1 in healthy cells, reflecting the cellular redox potential (approximately -260 to -150 mV) and signaling oxidative stress when shifted toward oxidation.^[45] GSH concentrations, ranging from 1–2 mM in most cells to up to 10 mM in hepatocytes, position it as the predominant low-molecular-weight thiol, comprising the majority of the cellular non-protein sulfhydryl pool and serving as a primary buffer against oxidants.^[1] Evolutionarily, GSH emerged as a primordial antioxidant in cyanobacteria, where it provided defense against ROS generated by oxygenic photosynthesis and UV radiation, with conserved roles extending to higher eukaryotes for redox homeostasis and stress adaptation.^[46]

Conjugation and Detoxification

Glutathione serves a vital function in phase II detoxification by undergoing enzymatic conjugation with electrophilic compounds, rendering them less reactive and facilitating their elimination from cells. This process is primarily catalyzed by glutathione S-transferases (GSTs), a superfamily of enzymes that promote the nucleophilic addition of the glutathione thiolate anion to electrophilic centers in substrates. The canonical reaction is represented as GSH + R-X → GS-R + HX, where R-X denotes an electrophile and HX is the leaving group, resulting in a thioether-linked conjugate (GS-R) that enhances solubility for transport and excretion.^[47]^[48] In humans, the GST superfamily encompasses more than 20 isoforms, encoded by multiple genes and organized into cytosolic classes such as Alpha, Mu, Pi, Theta, and others based on sequence homology, structure, and substrate specificity. These isoforms exhibit tissue-specific expression patterns that align with localized detoxification needs; for instance, the Pi class is highly expressed in lung tissue, where it contributes to the inactivation of inhaled carcinogens and environmental toxins.^[48]^[49] GST-mediated conjugation targets a diverse array of substrates, including endogenous electrophiles like leukotrienes—lipid-derived signaling molecules—and exogenous agents such as the analgesic acetaminophen and various pesticides. Following conjugation, the GS-R adducts are sequentially processed by γ-glutamyl transpeptidase and cysteine conjugate β-lyase to form N-acetylcysteine conjugates known as mercapturic acids, which are readily excreted in urine via ATP-dependent transporters. This pathway is essential for mitigating toxicity from both metabolic byproducts and environmental exposures.^[50]^[47] The kinetics of GST-catalyzed reactions typically follow Michaelis-Menten behavior, with low affinity constants (Km) for glutathione (often around 100 μM) ensuring efficient conjugation even at physiological GSH concentrations. For example, using 1-chloro-2,4-dinitrobenzene (CDNB) as a model electrophilic substrate, representative Vmax values range from 40 to 60 μmol/min per mg of enzyme, varying by isoform and tissue source. These parameters underscore the enzymes' capacity to handle high substrate loads during acute toxic challenges.^[51]^[48] Genetic polymorphisms in GST genes significantly influence detoxification efficiency, altering enzyme activity and susceptibility to toxin-related diseases. Null deletions in GSTM1 and GSTT1 abolish functional protein expression, reducing overall conjugative capacity, while variants in GSTP1 (e.g., Ile105Val) modify substrate specificity and catalytic rates, such as diminished activity toward certain carcinogens or chemotherapeutic agents. These polymorphisms have been linked to inter-individual variations in responses to environmental toxins and drug metabolism.^[52]^[47]

Regulation and Metabolism

Cellular Regulation

Intracellular glutathione (GSH) levels are tightly regulated to maintain cellular homeostasis, primarily through control of its biosynthesis, the rate-limiting step of which is catalyzed by γ-glutamylcysteine synthetase (also known as glutamate-cysteine ligase, GCL). A key mechanism is feedback inhibition, where GSH competitively inhibits GCL with respect to glutamate, with an inhibition constant (Ki) of approximately 2.3 mM, preventing excessive accumulation and ensuring balanced synthesis under normal conditions.^[13] Transcriptional regulation further fine-tunes GSH production in response to environmental cues, particularly oxidative stress. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a central role, as Nrf2 translocates to the nucleus upon stress-induced dissociation from its inhibitor Keap1, binding to antioxidant response elements (AREs) in the promoter regions of genes encoding GCL subunits and glutathione S-transferases (GSTs), thereby upregulating their expression to boost GSH synthesis and conjugation capacity.^[53] Membrane transport proteins contribute to GSH homeostasis by modulating intracellular concentrations through export and import. Exporters such as multidrug resistance-associated protein 1 (MRP1) actively pump oxidized glutathione (GSSG) and GSH-conjugates out of cells using ATP, helping to alleviate oxidative burden and prevent toxicity. Conversely, organic anion-transporting polypeptides (OATPs), including OATP1B3, facilitate GSH uptake into cells, supporting replenishment in tissues with high demand, such as the liver.^[54]^[55] Hormonal signals influence hepatic GSH synthesis, with insulin promoting it by enhancing GCL activity and expression, while glucagon inhibits this process, leading to reduced GSH levels. These effects help coordinate GSH dynamics with metabolic states, such as postprandial glucose handling.^[56] GSH levels decline with aging and in pathological conditions like diabetes, contributing to heightened oxidative stress. In healthy aging, plasma and tissue GSH concentrations decrease due to impaired synthesis, while in diabetes, hyperglycemia suppresses GCL expression, resulting in deficient GSH production and exacerbated complications.^[57]^[58]

Redox Cycling

Glutathione participates in a dynamic redox cycling process that maintains cellular antioxidant capacity by regenerating its reduced form (GSH) from the oxidized disulfide (GSSG). In this cycle, GSH is first oxidized to GSSG by glutathione peroxidases (GPx), which utilize GSH to reduce hydrogen peroxide and lipid hydroperoxides to water and alcohols, respectively. The resulting GSSG is then reduced back to two molecules of GSH through the action of NADPH-dependent glutathione reductase (GR), linking the cycle to the cell's reducing power. The overall reaction catalyzed by GR is:

\text{GSSG} + \text{NADPH} + \text{H}^+ \rightarrow 2\text{GSH} + \text{NADP}^+

This step consumes one NADPH per GSSG molecule reduced. Since GPx activity oxidizes two GSH to one GSSG, one NADPH is consumed per complete cycle regenerating two GSH. NADPH is primarily supplied by the pentose phosphate pathway, particularly via glucose-6-phosphate dehydrogenase, ensuring sustained flux through the cycle under oxidative conditions.^[59] The redox cycle operates in distinct cellular compartments, with separate pools of GSH and GSSG in the cytosol and mitochondria to address compartment-specific oxidative challenges. In the cytosol, GR and GPx maintain a high GSH/GSSG ratio, while mitochondria rely on a dedicated GSH transport system and mitochondrial isoforms of related enzymes, such as glutaredoxin-2, to support localized redox buffering despite lower overall GSH concentrations. Although GR is encoded by a single gene (GSR), its activity is compartmentalized, with mitochondrial GR contributing to the reduction of GSSG generated from superoxide dismutase-derived peroxides. This separation prevents cross-talk between compartments and allows tailored responses to stressors like mitochondrial respiration.^[45]^[59] Imbalances in the cycle, often marked by elevated GSSG levels and a decreased GSH/GSSG ratio (from a normal >100:1 to ≤10:1 under stress), signal oxidative overload and can lead to protein glutathionylation and disrupted redox signaling. The redox potential (E_h) of the GSH/GSSG couple, typically around -240 mV in healthy cells, shifts positively during such imbalances, reflecting a more oxidizing environment that compromises cellular homeostasis. Pharmacological agents like 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) inhibit GR by carbamoylating its active site, thereby disrupting the cycle, depleting GSH stores, and sensitizing cells to oxidative damage in experimental models of endothelial and tumor biology.^[59]^[45]^[60]

Specialized Roles

In Plant Physiology

In plant physiology, glutathione (GSH) is integral to stress adaptation, particularly through the ascorbate-glutathione cycle in chloroplasts, where it facilitates the detoxification of hydrogen peroxide (H₂O₂) generated during photosynthesis. This cycle operates via a series of enzymatic reactions involving ascorbate peroxidase (APX), which uses ascorbate to reduce H₂O₂ to water, producing monodehydroascorbate; monodehydroascorbate reductase (MDHAR), which regenerates ascorbate using NADPH; and dehydroascorbate reductase (DHAR), which recycles dehydroascorbate back to ascorbate with GSH as the electron donor, yielding oxidized glutathione (GSSG). The cycle maintains redox homeostasis under oxidative stress from environmental factors like high light or drought, preventing damage to photosynthetic machinery.^[61] In addition to direct ROS scavenging, GSH supports the regeneration of GSSG to GSH via glutathione reductase, ensuring sustained antioxidant capacity during prolonged stress exposure.^[62] GSH also contributes to heavy metal tolerance by serving as a precursor for phytochelatins, which are cysteine-rich peptides formed through the polymerization of GSH units catalyzed by phytochelatin synthase. These phytochelatins chelate toxic metals such as cadmium (Cd²⁺) and copper (Cu²⁺), forming stable complexes that are transported to vacuoles for sequestration, thereby reducing cytosolic metal concentrations and mitigating oxidative damage. This mechanism is particularly vital in hyperaccumulator plants, where elevated GSH levels correlate with enhanced metal detoxification and tolerance.^[63] For instance, under Cd exposure, phytochelatin synthesis rapidly depletes GSH pools, but this is counterbalanced by upregulated GSH biosynthesis to maintain cellular redox balance.^[64] Beyond detoxification, GSH participates in redox signaling via S-glutathionylation, a reversible post-translational modification where GSH conjugates to cysteine residues on proteins, modulating their activity in response to abiotic and biotic stresses. Under drought conditions, S-glutathionylation targets regulatory proteins, influencing gene expression related to stress-responsive pathways, such as those involving ethylene biosynthesis enzymes like 1-aminocyclopropane-1-carboxylate synthase.^[65] Similarly, during pathogen attack, this modification protects proteins from irreversible oxidation and fine-tunes defense signaling, including the activation of hypersensitive response genes.^[66] S-glutathionylation thus acts as a molecular switch, integrating GSH status with transcriptional regulation for adaptive responses.^[67] GSH influences plant development, including root growth and flowering, as evidenced by mutants defective in GSH biosynthesis. Arabidopsis gsh1 and gsh2 mutants, impaired in γ-glutamylcysteine synthetase and glutathione synthetase respectively, exhibit severely reduced primary root elongation and overall biomass accumulation due to disrupted cell cycle progression and meristem maintenance.^[68] These mutants also display chlorosis and delayed flowering, highlighting GSH's role in chlorophyll stabilization and hormonal signaling pathways that govern reproductive development. Exogenous GSH supplementation partially rescues these phenotypes, underscoring its essential function in developmental redox control.^[69] A notable difference from animal systems is the accumulation of GSSG in plants under high light stress, driven by photorespiration, which generates H₂O₂ in peroxisomes and elevates the GSSG/GSH ratio to signal acclimation. In contrast, animals maintain more stable GSH:GSSG ratios (typically 100:1) without equivalent photosynthetic or photorespiratory burdens, making plant GSH pools more dynamically responsive to light-induced redox shifts.^[70] This adaptation enables plants to balance energy production with stress defense under fluctuating environmental light conditions.^[71]

In Drug Delivery and Therapeutics

Glutathione (GSH) plays a pivotal role in drug delivery and therapeutics by exploiting its elevated concentrations in the tumor microenvironment, which can reach 2–10 mM intracellularly compared to 2–20 μM in normal extracellular fluids, enabling the design of stimuli-responsive carriers for site-specific drug release.^[72] This redox gradient allows GSH to reduce disulfide bonds in engineered nanoparticles, triggering degradation and payload liberation selectively within tumors.^[73] In therapeutics, strategies targeting GSH levels, either through depletion to enhance chemotherapy efficacy or direct supplementation to combat oxidative stress, have advanced toward clinical applications.^[74] In drug delivery systems, GSH facilitates the degradation of disulfide-linked nanoparticles, promoting controlled release of encapsulated therapeutics in high-GSH tumor environments. For instance, doxorubicin-loaded sodium alginate derivative nanoparticles exhibit minimal release under normal conditions but demonstrate selective and rapid doxorubicin liberation upon exposure to 10 mM GSH, mimicking tumor intracellular levels, with efficient uptake and cytotoxicity in cancer cells like HepG2 and HeLa while sparing healthy cells.^[75] Similarly, biodegradable polyurethane nanoparticles loaded with cisplatin show an eightfold increase in drug release at 10 mM GSH over 100 hours compared to GSH-free conditions, attributed to cleavage of disulfide crosslinks, thereby enhancing therapeutic index in lung cancer models.^[76] Therapeutic targeting of GSH often involves its depletion to sensitize cancer cells to chemotherapy by inhibiting key synthesis enzymes. Buthionine sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (the rate-limiting enzyme in GSH biosynthesis), depletes intracellular GSH by over 80% in multiple myeloma cell lines and xenografts, synergistically enhancing the cytotoxicity of melphalan with combination indices ≤0.7, achieving 2–4 logs of cell kill even in drug-resistant lines.^[74] Phase I clinical trials of continuous BSO infusion have confirmed >80% tumor GSH reduction, supporting its potential in combination regimens, though modest antitumor activity was observed when paired with low-dose alkylators in solid tumors.^[74] Direct GSH administration via intravenous routes has shown promise in neurodegenerative therapeutics, particularly for Parkinson's disease. In a clinical study, intravenous GSH doses of 1.4–5 g administered three times weekly for three weeks led to significant symptom improvements in Parkinson's patients, with benefits persisting 2–4 months post-treatment, likely due to enhanced antioxidant protection against oxidative damage.^[77] This approach elevates brain GSH levels, mitigating dopaminergic neuron loss, as corroborated in reviews of neuroprotective strategies up to 2023.^[78] Nanomedicine designs leverage GSH-responsive polymers to achieve site-specific drug release with tunable kinetics. These polymers, incorporating disulfide linkages, maintain structural integrity in circulation but undergo rapid disassembly in the reductive tumor milieu, reducing drug release half-life from hours in normal conditions to minutes upon GSH exposure, as seen in micellar systems where >90% payload release occurs within 24 hours at elevated GSH.^[79] Such designs, including amphiphilic triblock copolymers, enable controlled anticancer drug delivery with minimal off-target effects.^[80] A key challenge in GSH therapeutics is its poor oral bioavailability, stemming from rapid degradation by γ-glutamyl transferase (GGT) in the gastrointestinal tract and first-pass metabolism, resulting in plasma half-lives of approximately 2 minutes and absorption rates below 1%.^[81] This enzymatic hydrolysis limits systemic delivery, necessitating alternative routes like intravenous administration for efficacy.^[81]

Practical Applications

Medical Uses

Glutathione supplementation is available in oral, intravenous (IV), and liposomal forms, though oral bioavailability is generally low due to degradation in the gastrointestinal tract, prompting the use of liposomal formulations for improved absorption. IV administration bypasses these issues and is commonly employed for acute therapeutic needs, such as liver detoxification in nonalcoholic fatty liver disease (NAFLD), where doses of 300 mg per day have shown potential to reduce oxidative stress and improve liver enzyme levels in preliminary studies.^[82] Liposomal oral glutathione, at doses around 500 mg daily, has demonstrated elevations in systemic glutathione levels and enhancements in immune markers, offering a more effective alternative to standard oral supplements. However, the U.S. Food and Drug Administration (FDA) has highlighted concerns with compounded IV glutathione due to risks of contamination and lack of approval for injectable use.^[83] In clinical settings, glutathione serves as an adjunct therapy in cystic fibrosis, where inhaled or nebulized forms act as a mucolytic agent by breaking disulfide bonds in mucus, thereby improving mucociliary clearance and reducing airway obstruction. For HIV patients, glutathione supplementation helps restore immune cell redox balance and enhances macrophage function, potentially mitigating oxidative stress-related immune dysfunction observed in infection. Additionally, IV glutathione has been investigated for preventing chemotherapy-induced peripheral neuropathy, with randomized trials showing neuroprotective effects against oxaliplatin- and paclitaxel-based regimens by counteracting oxidative damage to nerves. Rare genetic deficiencies in glutathione synthesis, such as glutathione synthetase deficiency, lead to severe hemolytic anemia, metabolic acidosis, and neurological impairments due to impaired antioxidant defense and accumulation of toxic intermediates like 5-oxoproline. These autosomal recessive disorders typically manifest in infancy and require supportive treatments including blood transfusions and bicarbonate therapy to manage acidosis. Studies indicate potential benefits of glutathione or its precursors, such as N-acetylcysteine, in improving insulin sensitivity among individuals with type 2 diabetes, with supplementation enhancing insulin sensitivity without altering oxidative stress markers in obese patients.^[84] However, evidence for its efficacy in autism spectrum disorders remains mixed, with pilot studies showing tolerability and modest reductions in behavioral symptoms but lacking robust support from larger trials, while results for age-related conditions are inconclusive due to heterogeneous study designs. Glutathione holds Generally Recognized as Safe (GRAS) status from the FDA for use in food products at specified levels, and therapeutic supplementation is generally well-tolerated, though high doses may cause zinc depletion, gastrointestinal discomfort, or, in inhaled forms, bronchospasm in susceptible individuals.

Industrial and Food Uses

Glutathione is employed in winemaking as an antioxidant to prevent oxidation and stabilize color, particularly in white wines, where it is added at concentrations up to 20 mg/L.^[85] This application has been approved by the International Organisation of Vine and Wine since 2015 and incorporated into EU regulations thereafter, allowing its use in must and during wine aging to mitigate oxidative damage without relying solely on sulfur dioxide.^[86] In practice, reduced glutathione (GSH) helps preserve varietal aromas and limits browning by scavenging reactive oxygen species.^[87] In food processing, glutathione serves as a dough conditioner by facilitating thiol-disulfide exchange reactions, which enhance gluten elasticity and improve dough handling properties during mixing.^[88] This mechanism involves the interchange between glutathione's thiol groups and disulfide bonds in wheat proteins, leading to a more extensible gluten network suitable for bread production.^[89] Additionally, glutathione acts as a preservative in fruits and juices, inhibiting enzymatic and non-enzymatic browning reactions that degrade quality during storage and processing.^[90] For instance, its addition to apple or grape juice suppresses polyphenol oxidase activity and reduces color changes, extending shelf life without imparting unwanted flavors.^[91] In the cosmetics industry, topical glutathione is utilized for skin lightening due to its inhibition of tyrosinase, the key enzyme in melanin synthesis, thereby reducing hyperpigmentation.^[92] Formulations typically contain up to 2% glutathione, applied as creams or serums, with studies showing improved skin brightness after consistent use over several weeks.^[93] This application leverages glutathione's antioxidant properties to shift melanin production toward lighter pheomelanin variants.^[94] Biotechnological production of glutathione relies on microbial fermentation using organisms such as Saccharomyces cerevisiae or Escherichia coli, engineered to overexpress biosynthetic pathways for yields exceeding 10 g/L under optimized conditions.^[95] These processes involve fed-batch fermentation with glucose-based media, achieving high productivity through metabolic engineering of enzymes like γ-glutamylcysteine synthetase.^[96] The global glutathione market, driven by these production methods, was valued at approximately $253 million in 2024.^[97] Regulatory oversight recognizes glutathione as generally recognized as safe (GRAS) for food use by the U.S. Food and Drug Administration, permitting incorporation in various categories such as meat products and beverages at levels up to 300 mg per serving.^[98] However, in beverages like wine or juice, concentrations are limited to avoid off-flavors, with optimal levels below those causing sensory defects such as bitterness or astringency.^[99]

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[6]
[PDF] Glutathione: A small molecule with big sense
Aug 8, 2018 · The most important aspect of GSH is its thiol group; in fact, it is the main source of non-protein thiols for the majority of aerobic organisms.
[7]
Glutathione Disulfide - an overview | ScienceDirect Topics
Fig. 2. Structures of reduced glutathione (GSH) and glutathione disulfide (GSSG). The tripeptide glutathione is composed of glycine, cysteine, and glutamate.Antioxidants · Glutathione And... · 3.1 Disulfide Bond Formation...<|control11|><|separator|>
[8]
Glutathione: new roles in redox signaling for an old antioxidant
Both GSSG and GSSR can be catalytically reduced back to GSH by the NADPH-dependent GSH reductase and thioredoxin (Trx)/glutaredoxin (Grx) system, respectively.
[9]
Copper-Catalyzed Glutathione Oxidation is Accelerated by the ...
Aug 5, 2022 · The cytosolic GSH/GSSG ratio is very high (>100), and its reduction can lead to apoptosis or necrosis, which are of interest in cancer research.
[10]
Redox status expressed as GSH:GSSG ratio as a marker for ...
Reduced glutathione (GSH) is considered to be one of the most important scavengers of reactive oxygen species (ROS), and its ratio with oxidised glutathione ( ...
[11]
An isocratic HPLC-UV analytical procedure for assessment of ...
Oct 15, 2024 · The UV detector was set to a wavelength of 210 nm ... Determination of glutathione and glutathione disulfide in biological samples: an in-depth ...
[12]
Kinetic study of the oxidation mechanism of glutathione by hydrogen ...
Key words: glutathione, hydrogen peroxide, kinetic mechanism, glutathione disulfide. ... 250 nm and 305 nm. The absorption band at 250 nm increases.
[13]
GLUTATHIONE SYNTHESIS - PMC - PubMed Central - NIH
Synthesis of GSH occurs via a two-step ATP-requiring enzymatic process. The first step is catalyzed by glutamate-cysteine ligase (GCL), which is composed of ...Missing: original paper
[14]
Glutathione Homeostasis and Functions: Potential Targets for ...
Feb 28, 2012 · The first step, catalyzed by γGLCL, is the rate-limiting step for overall GSH biosynthesis process. The enzyme is inhibited by GSH, the end ...
[15]
Interactions between biosynthesis, compartmentation and transport ...
Enzymes and genes. The pathway of glutathione biosynthesis is well established and is similar in plants, animals and micro‐organisms. In two ATP‐dependent steps ...
[16]
Plant Glutathione Biosynthesis: Diversity in Biochemical ... - Frontiers
Sep 4, 2011 · Two enzymes catalyze glutathione synthesis: glutamate–cysteine ligase, and glutathione synthetase. Glutathione is a ubiquitous protective ...
[17]
The Non-Essential Amino Acid Cysteine Becomes ... - PubMed Central
May 16, 2019 · Glutathione is composed of glycine, glutamate, and cysteine, with cysteine being limiting for glutathione synthesis in normal tissues.
[18]
Blood glutathione synthesis rates in healthy adults receiving a sulfur ...
The availability of cysteine is thought to be the rate limiting factor for synthesis of the tripeptide glutathione (GSH), based on studies in rodents.Missing: biosynthesis | Show results with:biosynthesis
[19]
Nucleus-translocated GCLM promotes chemoresistance in ... - Nature
Jan 2, 2025 · As a modifier subunit, GCLM directly interacts with the glutamate cysteine ligase (GCL) catalytic subunit (GCLC) to modify the catalytic ...
[20]
Genomic analyses reveal a conserved glutathione homeostasis ...
The present study reveals that core genes in the C. intestinalis genome contributing to the biosynthesis of glutathione (Gclc, Gclm, Gss, Ggt1, Slc7a11) ...
[21]
Transcription of genes involved in glutathione biosynthesis in the ...
These genes exhibit a good level of sequence conservation with metazoan homologs generally, especially for residues important for the activity of the enzymes.
[22]
Cellular Compartmentalization, Glutathione Transport and Its ... - NIH
Its half-life is 4 days in human erythrocytes, 2 to 4 h in the cytosol of rat hepatic cells and 30 h in the mitochondrial lumen [43].
[23]
The Emerging Roles of γ-Glutamyl Peptides Produced by γ ...
Dec 13, 2023 · Although GGT had long been considered a unique enzyme with γ-glutamyl bond-cleaving activity, particularly with respect to glutathione ...
[24]
The importance of glutathione in human disease - PMC - NIH
Reduced glutathione (GSH) is the most prevalent non-protein thiol in animal cells. Its de novo and salvage synthesis serves to maintain a reduced cellular ...
[25]
Glutathione metabolism in cancer progression and treatment ...
Jun 18, 2018 · GSH is the predominant form, existing in millimolar concentrations in most cells (liver 5–10 mM; Wu et al., 2004). ... glutathione content ...
[26]
Glutathione Synthesis and Turnover in the Human Erythrocyte
Whole erythrocytes were prepared with initial GSH concentrations ranging from the normal cytoplasmic concentration of ∼2.3 down to 0.2 mmol(liter of ...
[27]
Minimizing Oxidative Stress in the Lens: Alternative Measures for ...
GSH levels in the lens exist at ~4–6 mM, which is higher than any other ocular tissue [41], being around nine times higher than that in the cornea [42].
[28]
Dual localization of glutathione S‐transferase in the cytosol and ...
Sep 19, 2011 · Almost 85–90% of cellular GSH is present in the cytosol, 10%–15% in the mitochondria (equivalent to 10–12 mm, considering the volume of ...
[29]
A mathematical model of glutathione metabolism
Apr 28, 2008 · Plasma concentrations in humans are reported in the range 2–20 μM for GSH [1, 13, 14], and 0.14–0.34 μM for GSSG [13, 14, 42]. The average ...
[30]
A Simple HPLC-UV Method for the Determination of Glutathione in ...
A highly sensitive and simple HPLC-UV method was developed and validated for the assay of glutathione (GSH) in PC-12 cells.
[31]
Comparison of HPLC and Enzymatic Recycling Assays for the ...
GSSG levels found using the HPLC-UV assay were 200-fold higher than those obtained with the enzymatic recycling procedure. Reduction of synthetic GSSG by ...
[32]
Glutathione Synthesis Rates in Early Postnatal Life - Nature
This study investigated the mechanism behind this increased GSH concentration by determining GSH synthesis in the first days after birth.
[33]
Cord Blood Glutathione Depletion in Preterm Infants - PubMed Central
Nov 16, 2011 · Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants. Our aim was to determine: 1) whether GSH ...
[34]
Comparison of glutathione levels in rodent and human tumor cells ...
Jul 1, 1988 · Cellular glutathione (GSH) levels were compared in human and rodent tumor cells grown both in vivo and in vitro. Three human (A431, HEp3, ...
[35]
Organelle-specific localization of glutathione in plants grown under ...
Apr 29, 2022 · The reported chloroplast and vacuole glutathione concentration differs markedly among plant species (0.5–5 mM and 0.08–0.7 mM, respectively) ...
[36]
Increased intracellular H₂O₂ availability preferentially drives ...
Increased intracellular H₂O₂ availability preferentially drives glutathione accumulation in vacuoles and chloroplasts. Plant Cell Environ. 2011 Jan;34(1):21-32.
[37]
The role of glutathione in periplasmic redox homeostasis and ... - NIH
In E. coli, cytosolic GSH levels have been described to be in the millimolar range (up to 10 mM).
[38]
Isolation of glutathione biosynthesis-deficient mutants of ...
The intracellular glutathione concentration of mutant strain S. cerevisiae 3033 was 0.0172 g/g dry weight, which was a decrease of >76% compared to that of the ...
[39]
Biosynthesis and Functions of Mycothiol, the Unique Protective Thiol ...
Summary: Mycothiol (MSH; AcCys-GlcN-Ins) is the major thiol found in Actinobacteria and has many of the functions of glutathione, which is the dominant thiol in ...
[40]
The Glutathione System: A Journey from Cyanobacteria to Higher ...
From bacteria to plants and humans, the glutathione system plays a pleiotropic role in cell defense against metabolic, oxidative and metal stresses.
[41]
Glutathione Is a Key Player in Metal-Induced Oxidative Stress ...
This redox regulation probably contributes to the well established upregulation of GSH synthesis in response to oxidative stress conditions like metal toxicity.
[42]
Quantitative in vivo measurement of glutathione in Arabidopsis cells
Dec 23, 2001 · A new, non-destructive assay is described to quantify cytoplasmic glutathione (GSH) levels in vivo in single cells or populations of cells from Arabidopsis ...
[43]
Quantitative in vivo measurement of glutathione in Arabidopsis cells
A new, non-destructive assay is described to quantify cytoplasmic glutathione (GSH) levels in vivo in single cells or populations of cells from Arabidopsis ...
[44]
Hydrogen Exchange Equilibria in Glutathione Radicals: Rate ...
Sep 30, 2010 · (42), the spectral characteristics of αC- and βC-type radicals are different, with αC-radicals exhibiting maximal absorbance at ca. 265 nm and β ...
[45]
Glutathione: new roles in redox signaling for an old antioxidant - PMC
On the other hand, GSH does not react directly non-enzymatically with hydroperoxides. In fact, its role as a co-substrate for the selenium-dependent GPX has ...
[46]
The Glutathione System: A Journey from Cyanobacteria to Higher ...
From bacteria to plants and humans, the glutathione system plays a pleiotropic role in cell defense against metabolic, oxidative and metal stresses.
[47]
The Multifaceted Role of Glutathione S-Transferases in Health ... - NIH
Apr 18, 2023 · As principal phase II detoxification enzymes, GSTs protect living cells by catalyzing the conjugation of glutathione (GSH) to a wide variety ...
[48]
Structure, function and evolution of glutathione transferases - NIH
This review surveys the classification of GSTs in non-mammalian sources, such as bacteria, fungi, plants, insects and helminths
[49]
Glutathione S-transferases--a review - PubMed
The Glutathione S-transferases (GSTs) form a group of multi-gene isoenzymes involved in the cellular detoxification of both xenobiotic and endobiotic compounds.
[50]
Glutathione transferases: substrates, inihibitors and pro-drugs in ...
Jan 24, 2018 · Glutathione transferase classical GSH conjugation activity plays a critical role in cellular detoxification against xenobiotics and noxious compounds as well ...
[51]
Electrochemical evaluation of glutathione S-transferase kinetic ...
A value of KM~100μM was obtained for either GSH or CDNB, and Vmax varied between 40 and 60μmol/min per mg of GST.
[52]
Glutathione-S-Transferases As Determinants of Cell Survival ... - NIH
Apr 29, 2012 · The family of glutathione S-transferases (GSTs) is part of a cellular Phase II detoxification program composed of multiple isozymes with functional human ...Detoxification · Signal Transduction · Gst Polymorphisms
[53]
An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation
In response to oxidative stress, Nrf2 translocates to the nucleus and activates the transcription of several antioxidant genes, such as glutathione biosynthetic ...
[54]
Transport of glutathione and glutathione conjugates by MRP1
In addition to drugs and GSH conjugates, MRP1 exports GSH and GSH disulfide, and might thus have a role in cellular responses to oxidative stress.Missing: GSSG GS- OATPs importers uptake
[55]
OATP8/1B3-mediated Cotransport of Bile Acids and Glutathione
In conclusion, although both OATP-C/1B1 and OATP8/1B3 are highly expressed, and able to transport bile acids, their mechanisms of action are different. OATP-C/ ...
[56]
Insulin and glucocorticoid dependence of hepatic gamma ...
We reported that glucagon and phenylephrine decrease hepatocyte GSH by inhibiting gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH ...Missing: modulate | Show results with:modulate
[57]
Deficient synthesis of glutathione underlies oxidative stress in aging ...
Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. ... Low blood glutathione levels in healthy aging ...
[58]
Glutathione Synthesis Is Diminished in Patients With Uncontrolled ...
Sustained hyperglycemia is associated with low cellular levels of the antioxidant glutathione (GSH), which leads to tissue damage attributed to oxidative stress ...
[59]
Glutathione in Cellular Redox Homeostasis - PubMed Central - NIH
This review focuses on the antioxidant system's roles in maintaining redox homeostasis. Especially, glutathione (GSH) is the most important thiol-containing ...
[60]
Glutathione redox cycle protects cultured endothelial cells ... - NIH
Endothelial glutathione reductase was selectively inhibited with 1,3-bis(chloroethyl)-1-nitrosourea (BCNU). Cellular stores of reduced glutathione were depleted ...
[61]
Physiological and biochemical mechanisms associated with ...
Jun 15, 2015 · The ascorbate-glutathione cycle involves a series of reactions with four enzymes (APX, MDHAR, DHAR and GR) that act in concert in H2O2 ...Results · Cu Content In Roots And... · Gsh Content And Gsh To...
[62]
Catalase, superoxide dismutase and ascorbate-glutathione cycle ...
Nov 7, 2018 · The study was performed to explore physiological, non-enzymatic and enzymatic detoxification pathways of reactive oxygen species (ROS) in tolerance of ...
[63]
Designing yeast as plant-like hyperaccumulators for heavy metals
Nov 8, 2019 · One of the main mechanisms found in plants for metal detoxification is the production of phytochelatins, oligomers of glutathione (GSH) with ...
[64]
Quantitative Relationship between Cadmium Uptake and ... - Nature
Oct 25, 2016 · Heavy metals activate the synthesis of phytochelatins (PCs), while the induced PCs might affect metal uptake via chelating intracellular ...
[65]
Glutathione Regulates 1-Aminocyclopropane-1-Carboxylate ...
In addition, we also identified the ACO1 protein to be a subject for S-glutathionylation, which is consistent with our in silico data. However, S- ...
[66]
Sulfenome mining in Arabidopsis thaliana - PNAS
Jul 21, 2014 · ... S-glutathionylation, a protein modification that protects the protein against oxidative damage. ... expression of numerous stress response genes ...
[67]
Sulfur Partitioning between Glutathione and Protein Synthesis ...
These direct feedback mechanism may include S-nitrosylation, S-glutathionylation ... stress-related events, defense gene expression, and the hypersensitive ...
[68]
Arabidopsis mutants impaired in glutathione biosynthesis exhibit ...
Jun 28, 2018 · We show that A. thaliana GSH1 and GSH2 mutants, affected in the biosynthesis of glutathione, have reduced root growth and total biomass ...Missing: flowering chlorosis
[69]
Maturation of Arabidopsis Seeds Is Dependent on Glutathione ... - NIH
Root growth of rml1 mutants can be rescued by germinating seeds on agar medium containing GSH (Vernoux et al., 2000). To test whether gsh1-T1 mutants could ...Missing: flowering | Show results with:flowering
[70]
Comparison of Light Condition-Dependent Differences in the ... - MDPI
With increasing light intensity, the amount of its reduced (GSH) and oxidized (GSSG) form and the GSSG/GSH ratio increased in the leaf extracts of both species ...
[71]
The glutathione system as a stress marker in plant ecophysiology
In the present review the hypothesis that stress responses of the glutathione system follow a general ecophysiological stress-response concept is investigated.
[72]
Application of glutathione depletion in cancer therapy
The concentration of intracellular GSH is around 2–10 mM, which is about 1000 folds higher than that in extracellular environment (2–10 μM) [9,10]. This GSH ...
[73]
Tumor Microenvironment-Stimuli Responsive Nanoparticles for ...
Dec 17, 2020 · This review provides a summary of different types of internal (pH, redox, enzyme, ROS, hypoxia) stimuli-responsive nanoparticle drug delivery systems
[74]
The glutathione synthesis inhibitor buthionine sulfoximine ... - Nature
Jul 18, 2014 · Phase I trials of continuous infusion of BSO induced >80% depletion of tumor GSH compared with pretreatment levels, but the modest activity of ...<|separator|>
[75]
Glutathione-responsive nanoparticles based on a sodium alginate ...
The doxorubicin loaded crosslinked nanoparticles (DOX-NPs) demonstrated selective drug release in 10 mM glutathione and the further study of their cellular ...Missing: microenvironment | Show results with:microenvironment
[76]
Glutathione-responsive biodegradable polyurethane nanoparticles ...
Stimuli-responsive polymers and nanoparticles, which respond to exogenous or endogenous stimuli in the tumor microenvironment, have been widely investigated for ...
[77]
https://pubmed.ncbi.nlm.nih.gov/8938817/
[78]
Glutathione: Pharmacological aspects and implications for clinical ...
Mar 21, 2023 · For example, the GSH intravenous administration in patients with Parkinson's disease determined significant improvements, which lasted for 2–4 ...
[79]
Visualization and Quantification of Drug Release by GSH ...
GSH could synergistically promote the disassembly of the micellar structure, resulting in accelerated probe and drug release of up to about 93.1% after 24 h.
[80]
Reduction‐responsive polymers for drug delivery in cancer therapy ...
Nov 5, 2020 · In this review article, we discussed the rationale behind the development of reduction-responsive polymers as drug delivery systems and highlight examples of ...
[81]
Enhancing the Oral Bioavailability of Glutathione Using Innovative ...
Mar 18, 2025 · Compound 1.70 demonstrated superior resistance to enzymatic degradation, as well as showing enhanced cell viability and improved antioxidant ...
[82]
Role of glutathione in winemaking: a review - PubMed
In this review, special emphasis is given to its occurrence in grapes, must, and wine and its role as an antioxidant in wine.
[83]
https://www.fda.gov/drugs/human-drug-compounding/fda-highlights-concerns-using-dietary-ingredient-glutathione-compound-sterile-injectables
[84]
Role of Glutathione in Winemaking: A Review - ResearchGate
Aug 6, 2025 · In this review, special emphasis is given to its occurrence in grapes, must and wine and its role as an antioxidant in wine.
[85]
Effect of ascorbic acid in dough: reaction of oxidized glutathione with ...
During dough mixing they are converted to protein-protein disulfides or glutathione-protein mixed disulfides by thiol/disulfide interchange reactions.Missing: conditioning elasticity<|separator|>
[86]
Effect of Ascorbic Acid in Dough: Reaction of Oxidized Glutathione ...
Aug 6, 2025 · During dough mixing they are converted to protein-protein disulfides or glutathione-protein mixed disulfides by thiol/disulfide interchange ...
[87]
Glutathione suppresses the enzymatic and non-enzymatic browning ...
This study aims to investigate the efficacy of glutathione as a browning inhibitor for use on grape juice. Grape juice browning treated with glutathione was ...Missing: preservative preservation
[88]
Preparation of Canned Apple Juice Using Glutathione as an ...
Apr 15, 2016 · This study investigated the effect of glutathione on canned apple juice browning during processing and storage.Missing: preservative | Show results with:preservative<|separator|>
[89]
Skin-whitening and skin-condition-improving effects of topical ... - NIH
Oct 17, 2014 · Reduced glutathione (GSH) has a skin-whitening effect in humans through its tyrosinase inhibitory activity, but in the case of oxidized ...
[90]
Glutathione as a skin‐lightening agent and in melasma: a systematic ...
Oct 23, 2024 · The combination of topical 2% glutathione plus oral glutathione was superior to monotherapy alone. ... inhibition of tyrosinase being the most ...
[91]
Glutathione: The master antioxidant – Beyond skin lightening agent
The thiol group of glutathione chelates copper ions on the active site of enzyme tyrosinase thus inhibiting it. The second mechanism by which glutathione causes ...
[92]
Enhancement of glutathione production in Saccharomyces ...
Currently, glutathione is produced industrially through a fermentation process using Saccharomyces cerevisiae with high glutathione content. However, the ...
[93]
Efficient production of glutathione in Saccharomyces cerevisiae via ...
Nov 3, 2022 · In S. cerevisiae, glutathione is present in two forms: GSH and GSSG. Of the two forms, the GSH concentration is much higher than that of GSSG ...
[94]
Glutathione Market Size, Growth Opportunity 2025-2034
The global glutathione market was valued at USD 252.9 million in 2024 and is estimated to grow at a CAGR of over 6.8% from 2025 to 2034.
[95]
GRAS Notices - cfsanappsexternal.fda.gov
Glutathione ; Ingredient in several food categories, including meat products, at levels ranging from 5 to 300 milligrams per serving; and in milk- and soy-based ...
[96]
Evaluating the Potential of Gamma‐Glutamylcysteine and ...
Feb 17, 2025 · Low amounts of glutathione have been shown to preserve flavor components, while high levels ... off-flavors in wine (Wegmann-Herr et al.