This is a working overview of glutathione, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-07-27 and is reviewed periodically as new material appears.
Glutathione is a tripeptide composed of glutamate, cysteine, and glycine. It occurs in nearly all living cells, with highest concentrations in liver, kidney, and red blood cells, and exists in reduced (GSH) and oxidized disulfide (GSSG) forms. The cysteine thiol group enables reversible oxidation and reduction reactions. This property makes glutathione a central participant in cellular redox balance. The balance between these forms is often used as an indicator of oxidative stress.
Glutathione synthesis proceeds in two ATP-dependent steps catalyzed by glutamate-cysteine ligase and glutathione synthetase. The first step joins glutamate and cysteine to form gamma-glutamylcysteine and is generally rate-limiting. The second step adds glycine to complete the tripeptide. Cysteine availability, feedback inhibition by glutathione, and oxidative conditions influence flux through this pathway. The pathway is conserved across many organisms, and degradation by gamma-glutamyl transpeptidase and related peptidases recycles amino acids for new synthesis.
Glutathione is a small sulfur-containing peptide built from glutamic acid, cysteine, and glycine. Its distinctive feature is a gamma-glutamyl bond between glutamate's side-chain carboxyl group and cysteine's amino group. This linkage resists ordinary peptidases and helps the molecule remain stable inside cells. The reduced thiol form, often abbreviated GSH, is the dominant intracellular species. The oxidized disulfide dimer, GSSG, forms when two reduced molecules link through their cysteine sulfur atoms. The balance between these forms is a common redox indicator.
In living systems, glutathione occurs in millimolar concentrations in many cell types, while extracellular levels are generally much lower. The liver holds a substantial share of the body's total pool, and the molecule participates in reduction, detoxification, and amino acid transport. It also serves as a cofactor for enzymes such as glutathione peroxidase and glutathione S-transferase. Because the cysteine residue supplies a reactive thiol, glutathione can donate electrons and become oxidized. Cells regenerate reduced glutathione through glutathione reductase using NADPH.
| Property | Value | Notes |
|---|---|---|
| Common name | Glutathione | Reduced form is abbreviated GSH |
| Chemical class | Tripeptide | Composed of glutamate, cysteine, and glycine |
| Molar mass | 307.32 g/mol | For reduced glutathione |
| CAS Registry Number | 70-18-8 | For reduced L-glutathione |
| Appearance | White crystalline powder | Typical solid reference material |
Glutathione is a small tripeptide composed of glutamate, cysteine, and glycine, with the unusual gamma-glutamyl linkage between glutamate and cysteine. Its cysteine thiol group makes it a major non-enzymatic antioxidant in cells. The reduced form, GSH, predominates in most intracellular compartments, while the oxidized disulfide form, GSSG, is produced when GSH reduces reactive oxygen species. Intracellular concentrations often reach millimolar levels, whereas plasma concentrations are much lower, typically in the low micromolar range. This gradient reflects active synthesis, transport, and consumption rather than passive distribution.
Synthesis occurs in two ATP-dependent steps: glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine, and glutathione synthetase adds glycine to complete the tripeptide. The pathway is feedback-inhibited by GSH and limited by cysteine availability, so cysteine supply often constrains production. Once formed, GSH participates in redox buffering, xenobiotic conjugation, and protein glutathionylation. Glutathione peroxidase uses GSH to reduce hydrogen peroxide and lipid peroxides, yielding GSSG, while glutathione reductase regenerates GSH using NADPH. Glutathione S-transferases conjugate electrophiles to GSH, supporting detoxification and excretion.
Glutathione reference materials are sensitive to oxygen, light, and elevated temperature. Solid material is typically stored desiccated at -20 °C or below, while solutions require tighter control because thiol oxidation proceeds faster in liquid form. Aqueous solutions are often prepared fresh, kept cold, and protected from air; some protocols add acid or chelating agents to slow metal-catalyzed oxidation. Repeated freeze-thaw cycles can accelerate degradation and should be avoided. Stability data vary by matrix, so laboratories usually verify performance with their own storage conditions.
Quality control for glutathione measurements includes calibration with authenticated standards, internal standards where available, blank correction, and spike recovery checks. Because glutathione can form during sample processing or degrade before analysis, pre-analytical handling is a major source of variability. Interlaboratory comparisons often show differences in reported values due to method-specific calibration and detection principles. Interpretive thresholds are context-dependent, and no single reference range applies across all tissues or matrices. Researchers generally report both reduced and oxidized forms, along with the method and sample handling details.
In 2008 a Congressional mandate called for investigators funded by the NIH to submit an electronic version of their final manuscripts to the National Library of Medicine's research repository, PubMed Central (PMC), no later than 12 months after the official date of publication. The NIH Public Access Policy was the first public access mandate for a U.S. public funding agency.
=== Targeting oxidative phosphorylation === Metabolic pathways can be targeted for clinically therapeutic uses. Within the mitochondrial metabolic network, for instance, there are various pathways that can be targeted by compounds to prevent cancer cell proliferation. One such pathway is oxidative phosphorylation (OXPHOS) within the electron transport chain (ETC). Various inhibitors can downregulate the electrochemical reactions that take place at Complex I, II, III, and IV, thereby preventing the formation of an electrochemical gradient and downregulating the movement of electrons through the ETC. The substrate-level phosphorylation that occurs at ATP synthase can also be directly inhibited, preventing the formation of ATP that is necessary to supply energy for cancer cell proliferation. Some of these inhibitors, such as lonidamine and atovaquone, which inhibit Complex II and Complex III, respectively, are currently undergoing clinical trials for FDA approval. Other non-FDA-approved inhibitors have still shown experimental success in vitro.
=== Alcohol use disorder === Naltrexone has been best studied as a treatment for alcoholism, or alcohol use disorder (AUD). Naltrexone has been shown to decrease the quantity and frequency of alcohol consumption by reducing the release of dopamine, a neurotransmitter associated with the euphoria that often accompanies alcohol use. Studies comparing naltrexone to a placebo have shown a small but statistically significant decrease in relapse likelihood. Its overall benefit has been described as "modest". Acamprosate may be more effective for AUD management overall, while naltrexone may decrease the desire for alcohol to a greater extent. A method pioneered by scientist John David Sinclair (dubbed commercially the "Sinclair Method") in the 1980s advocates "pharmacological extinction" of problem drinking behavior by administering naltrexone alongside controlled alcohol consumption. In effect, he argues that naltrexone-induced opioid antagonism sufficiently disrupts reflexive reward mechanisms inherent in the consumption of alcohol and, given enough repetition, will dissociate positive associations formerly made with the consumption of alcohol. A 2001 review of eight studies of naltrexone treatment in the setting of AUD concluded that, "although all found benefits from naltrexone with the coping therapy, none of them found any significant benefit of naltrexone over placebo when combined with support for abstinence."
Sources: en.wikipedia.org
Conduction velocity The speed at which an action potential travels along a nerve fiber. It is influenced by factors such as axon diameter and myelination. Consciousness A state of awareness of self and the environment. In neuroscience, it involves the coordinated activity of multiple brain regions, particularly the thalamocortical system. Corpus callosum The largest white matter structure in the brain, consisting of a thick band of axons that connects the left and right cerebral hemispheres. Cortical column A vertically organized group of neurons in the cerebral cortex that processes the same type of information, such as orientation or location in space. It is a basic functional unit of the cortex. Cortical plasticity The ability of the cerebral cortex to adapt and reorganize in response to experience, learning, or injury. Corticospinal tract A major descending pathway from the motor cortex to the spinal cord that mediates voluntary motor control, especially fine movements of the limbs. Creutzfeldt–Jakob disease (CJD) A rare and fatal neurodegenerative disorder caused by misfolded prion proteins. It leads to rapid cognitive decline, motor dysfunction, and ultimately death. Critical period A developmental window during which the nervous system is particularly sensitive to certain environmental stimuli, crucial for proper development of functions such as vision and language. Cross modal plasticity The ability of one sensory modality to reorganize and compensate in another’s absence (e.g., visual cortex being recruited for touch in individuals who are blind).
=== EC 1.2.2 With a cytochrome as acceptor === EC 1.2.2.1: formate dehydrogenase (cytochrome) EC 1.2.2.2: Now covered by EC 1.2.5.1, pyruvate dehydrogenase (quinone) EC 1.2.2.3: Now EC 1.17.2.3, formate dehydrogenase (cytochrome-c-553) EC 1.2.2.4: Now classified as EC 1.2.5.3, aerobic carbon monoxide dehydrogenase
Similar to water, graphite oxide easily incorporates other polar solvents, e.g. alcohols. However, intercalation of polar solvents occurs significantly different in Brodie and Hummers graphite oxides. Brodie graphite oxide is intercalated at ambient conditions by one monolayer of alcohols and several other solvents (e.g. dimethylformamide and acetone) when liquid solvent is available in excess. Separation of graphite oxide layers is proportional to the size of alcohol molecule. Cooling of Brodie graphite oxide immersed in excess of liquid methanol, ethanol, acetone and dimethylformamide results in step-like insertion of an additional solvent monolayer and lattice expansion. The phase transition detected by X-ray diffraction and differential scanning calorimetry (DSC) is reversible; de-insertion of solvent monolayer is observed when sample is heated back from low temperatures. An additional methanol and ethanol monolayer is reversibly inserted into the structure of Brodie graphite oxide under high pressure conditions. Hummers graphite oxide is intercalated with two methanol or ethanol monolayers at ambient temperature. The interlayer distance of Hummers graphite oxide in an excess of liquid alcohols increases gradually upon temperature decrease, reaching 19.4 and 20.6 Å at 140 K for methanol and ethanol, respectively. The gradual expansion of the Hummers graphite oxide lattice upon cooling corresponds to insertion of at least two additional solvent monolayers.
Sources: en.wikipedia.org
In 1996, the US had about 2 deaths per 10,000 motor vehicles, compared to 1.9 in Germany, 2.6 in France, and 1.5 in the UK. In 1998, there were 3,421 fatal crashes in the UK, the fewest since 1926; in 2010, this number was further reduced to 1,857 and was attributed to the 2009–2010 scrappage scheme. The sizable traffic safety lead enjoyed by the US since the 1960s had narrowed significantly by 2002, with the US improvement percentages lagging in 16th place behind those of Australia, Austria, Canada, Denmark, Finland, Germany, United Kingdom, Iceland, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Sweden, and Switzerland in terms of deaths per thousand vehicles, while in terms of deaths per 100 million vehicle miles travelled, the US had dropped from first place to tenth place. Transportation safety in the United States is monitored by various agencies.
Human ASH1L protein is 2969 amino acids long with a molecular weight of 333 kDa. ASH1L has an associated with SET domain (AWS), a SET domain, a post-set domain, a bromodomain, a bromo-adjacent homology domain, and a plant homeodomain finger (PHD finger). Human and Drosophila Ash1 share 66% and 77% similarity in their SET and PHD finger domains, respectively. A bromodomain is not present in Drosophila Ash1. The SET domain is responsible for ASH1L's histone methyltransferase (HMTase) activity. Unlike other proteins that contain a SET domain at their C terminus, ASH1L has a SET domain in the middle of the protein. The crystal structure of the human ASH1L catalytic domain, including the AWS, SET, and post-SET domains, has been solved to 2.9 angstrom resolution. The structure shows that the substrate binding pocket is blocked by a loop from the post-SET domain, and because mutation of the loop stimulates ASH1L HMTase activity, it was proposed that this loop serves a regulatory role.
CCL7 is a multipotent chemokine involved in anti-bacterial, anti-viral and anti-fungal immune responses. For example, CCL7-mediated stimulation of CCR2 chemokine receptors on monocytes is participating in the elimination of Listeria monocytogenes infections by the recruitment of monocytes and TNF/iNOS-producing dendritic cells (TipDCs). Next, the role of the CCL7 was also observed in the mouse infected by West Nile Virus. The genetically deficient mice in CCL7 have increased mortality because of decrease in monocytes and neutrophils. Early induction of CCL7 downstream of TLR9 signaling also promotes the development of robust immunity to cryptococcal infections. Diseases associated with CCL7 dysregulation are observed. For example, an abnormal increase of CCL7 worsens many disorders, like HIV or lesional psoriasis. Furthermore, CCL7 is implicated in various immunological diseases, as ulcerative colitis, multiple sclerosis or nonatopic and atopic asthma. It seems, that the expression of CCL7 can activate an antitumor immune response.
In the reaction 234U + n → 235U reaction, the 234U content of 4.5% enriched fuel drops steadily over the irradiation period falling from 450g/ton HM to 205g/ton HM in fuel with an irradiation of 60GWd/ton HM. Additionally, (n, 2n) reactions with fast neutrons also convert small amounts of 235U to 234U. This is countered by the rapid conversion of available 234U into 235U through thermal neutron capture. Uranium from spent nuclear fuel may contain as much as 0.010% 234U, or 100 parts per million, lower than the original fuel but still a higher fraction than natural uranium's 55 parts per million. Depleted uranium separated during the enrichment process contains much less 234U (around 0.001%), which reduces the alpha radioactivity almost half (the beta and gamma activity, which is from 234Th and 234Pa, is unchanged) compared to natural uranium having an equilibrium concentration of 234U in which an equal number of decays of 238U and 234U occur. Uranium-234, as well as uranium-232, is a byproduct, through further neutron capture, in reactors breeding thorium-232 into uranium-233.
Sources: en.wikipedia.org
GSH is the reduced thiol form, while GSSG is the disulfide-linked oxidized dimer. The GSH:GSSG ratio is used as a redox indicator, though the ratio can vary with sample handling and cell type.
Glutathione is present in many foods, including meats, poultry, fish, some vegetables, and fruits. Cooking, storage, and digestion affect the amounts available for absorption.
Yes, both enzymatic steps in glutathione synthesis consume ATP. The first step, catalyzed by glutamate-cysteine ligase, is usually rate-limiting.
It is a tripeptide rather than a full protein. Proteins generally contain many amino acids joined by alpha-peptide bonds, while glutathione has three residues and an unusual gamma-glutamyl linkage. That structure affects how enzymes recognize and break it down.