Glutathione
Identifiers
CAS number	70-18-8
PubChem	745
MeSH	Glutathione
SMILES	NC(CCC(=O)NC(CS)C(=O)NCC(O)=O)C(O)=O
Properties
Molecular formula	C10H17N3O6S
Molar mass	307.325
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Glutathione (GSH) is a tripeptide. It contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Glutathione, an antioxidant, protects cells from toxins such as free radicals.^[1] Image File history File links Glutathione-skeletal. ... Image File history File links Download high-resolution version (1100x554, 153 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Glutathione User:Benjah-bmm27/Gallery User:Ben Mills/Gallery ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... PubChem is a database of chemical molecules. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... The simplified molecular input line entry specification or SMILES is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings. ... A chemical formula is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... Molar mass is the mass of one mole of a chemical element or chemical compound. ... The plimsoll symbol as used in shipping In chemistry, the standard state of a material is its state at 1 bar (100 kilopascals exactly). ... A tripeptide is a peptide consisting of three amino acids, e. ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... This article is about the class of chemicals. ... Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ... A carboxyl or carboxylic group is a functional group consisting of a carbon atom and an oxygen atom doubly bonded to each other. ... Glutamate is the anion of glutamic acid. ... The term Side chain can have different meanings depending on the context: In chemistry and biochemistry a side chain is a part of a molecule attached to a core structure. ... Space-filling model of the antioxidant metabolite glutathione. ... In chemistry free radicals are uncharged atomic or molecular species with unpaired electrons or an otherwise open shell configuration. ...

Thiol groups are kept in a reduced state within ~5 mM in animal cells. In effect, glutathione reduces any disulfide bonds formed within cytoplasmic proteins to cysteines by acting as an electron donor. Glutathione is found almost exclusively in its reduced form, since the enzyme which reverts it from its oxidized form (GSSG), glutathione reductase, is constitutively active and inducible upon oxidative stress. In fact, the ratio of reduced to oxidized glutathione within cells is often used scientifically as a measure of cellular toxicity. Sulphydryl // In organic chemistry, a thiol is a compound that contains the functional group composed of a sulfur atom and a hydrogen atom (-SH). ... ed|other uses|reduction}} Illustration of a redox reaction Redox (shorthand for reduction/oxidation reaction) describes all chemical reactions in which atoms have their oxidation number (oxidation state) changed. ... For other uses, see Animal (disambiguation). ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the... In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. ... Cross section of cell with cytoplasm labeled at center right. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ... For other uses, see Electron (disambiguation). ... Glutathione reductase reduces oxidized glutathione Categories: ‪Science stubs‬ | ‪Enzyme stubs‬ | ‪Biochemistry stubs‬ | ‪Biochemistry‬ ... Oxidative stress is a medical term for damage to animal or plant cells (and thereby the organs and tissues composed of those cells) caused by reactive oxygen species, which include (but are not limited to) superoxide, singlet oxygen, peroxynitrite or hydrogen peroxide. ...

Biosynthesis

Glutathione is not an essential nutrient since it can be synthesized from the amino acids L-cysteine, L-glutamate and glycine. Cysteine is a naturally occurring hydrophobic amino acid which has a sulfhydryl group and is found in most proteins, however only in small quantities. ... Glutamic acid (Glu, E), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino acids. ... For the plant, see Glycine (plant). ...

It is synthesized in two adenosine triphosphate-dependent steps: Adenosine 5-triphosphate (ATP) is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer. ...

• first, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine via the enzyme gamma-glutamylcysteine synthetase (a.k.a. glutamate cysteine ligase, GCL). This reaction is the rate limiting step in glutathione synthesis.
• second, glycine is added to the C-terminal of gamma-glutamylcysteine via the enzyme glutathione synthetase.

Glutamate cysteine ligase (GCL) is a heterodimeric enzyme comprised of a catalytic (GCLC) and modulatory (GCLM) subunit. GCLC constitutes all the enzymatic activity, while GCLM increases the catalytic efficiency of GCLC. Mice lacking GCLC (ie all de novo GSH synthesis) die before birth.^[2] Mice lacking GCLM demonstrate no outward phenotype but exhibit marked decrease in GSH and increased sensitivity to toxic insults.^{[3] [4] [5]} Gamma-glutamylcysteine synthetase (EC 6. ... Glutathione synthetase (EC 6. ...

While all cells in the human body are capable of synthesizing glutathione, liver glutathione synthesis has been shown to be essential. Following birth, mice with genetically-induced loss of GCLC (ie GSH synthesis) only in the liver die within 1 month of birth.^[6]

The biosynthesis pathway for glutathione is found in some bacteria, like cyanobacteria and proteobacteria, but is missing in many other bacteria. Most eukaryotes synthesize glutathione, including humans, but some do not, such as legumes and some amoeba. The only archaea that make glutathione are halobacteria.^[7][8] Orders The taxonomy is currently under revision. ... Orders Alpha Proteobacteria    Caulobacterales - e. ... Subfamilies Faboideae Caesalpinioideae Mimosoideae References GRIN-CA 2002-09-01 The name Fabaceae belongs to either of two families, depending on viewpoint. ... Genera Haloarcula Halobacterium Halobaculum Halococcus Haloferax Halogeometricum Halorubrum Haloterrigena Natrialba Natrinema Natronobacterium Natronococcus Natronomonas Natronorubrum The halobacteria are a family of archaea, found in water saturated or nearly saturated with salt. ...

Function

Glutathione exists in a reduced (GSH) and oxidized (GSSG) state. In the reduced state, the thiol group of cysteine is able to donate an electron (H+) to other unstable molecules, such as reactive oxygen species. In donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to form glutathione disulfide (GSSG). Such a reaction is possible due to the relatively high concentration of gluathione in cells (up to 5mM in the liver). GSH can be regenerated from GSSG by the enzyme glutathione reductase.

In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than 10% exists in the disulfide form (GSSG). An increased GSSG/GSH ratio is considered indicative of oxidative stress.

GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals, as in the case of n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by paracetamol (or acetaminophen as it is known in the US), that becomes toxic when GSH is depleted by an overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide inhibitor and in the process detoxifies it, taking the place of cellular protein thiol groups which would otherwise be covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetyl-L-cysteine, which is processed by cells to L-cysteine and used in the de novo synthesis of GSH. For other uses, see Substrate. ... A chemically conjugated system, is a system of atoms covalently bonded with alternating single and double bonds (e. ... ed|other uses|reduction}} Illustration of a redox reaction Redox (shorthand for reduction/oxidation reaction) describes all chemical reactions in which atoms have their oxidation number (oxidation state) changed. ... This article or section is in need of attention from an expert on the subject. ... The cytosol (cf. ... In cell biology, a microsome is a small vesicle that is derived from fragmented endoplasmic reticulum (ER) produced when tissues such as liver are mechanically broken (homogenized). ... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... NAPQI is an acronym for the chemical N-acetyl-p-benzo-quinone imine. ... Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... A metabolite is the product of metabolism. ... Paracetamol (INN) (IPA: ) or acetaminophen (USAN), is the active metabolite of phenacetin, a so-called coal tar analgesic. ... Acetaminophen (USAN) or paracetamol (INN), is a popular analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. ... Suicide inhibition, also known as suicide inactivators and mechanism-based inactivators, is a form of irreversible enzyme inhibition that occurs when an enzyme binds a substrate analogue and forms a complex with it during the normal catalysis reaction. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ...

Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-Lactoyl-glutathione to glutathione and D-lactate. Leukotrienes are autocrine and paracrine eicosanoid lipid mediators derived from arachidonic acid by 5-lipoxygenase. ... A cofactor is any substance that needs to be present in addition to an enzyme to catalyze a certain reaction. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Glutathione peroxidase (PDB 1GP1, EC 1. ... The adjective hydrophilic describes something that likes water (from Greek hydros = water; philos = friend). ... This article or section does not cite its references or sources. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... Bile (or gall) is a bitter, yellow or green alkaline fluid secreted by hepatocytes from the liver of most vertebrates. ... Methylglyoxal, also called pyruvaldehyde or 2-oxo-propanal (CH3-CO-CH=O or C3H4O2) is the aldehyde form of pyruvic acid. ... The glyoxalase system is a set of enzymes that carry out the detoxification of methylglyoxal and the other reactive aldehydes that are produced as a normal part of metabolism. ...

Supplementation

Supplementing has been difficult as research suggests that glutathione taken orally is not well absorbed across the GI tract. In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, it was found that it is not possible to increase circulating glutathione in a clinically relevant way.^[9] However, glutathione concentrations can be raised by increased intake of the precursor cysteine. Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ...

Pathology

Excess glutamate at synapses, which may be released in conditions such as traumatic brain injury, can prevent the uptake of cysteine, a necessary building block of glutathione. Without the protection from oxidative injury afforded by glutathione, cells may be damaged or killed.^[10] Illustration of the major elements in a prototypical synapse. ... Traumatic brain injury (TBI), traumatic injuries to the brain, also called intracranial injury, or simply head injury, occurs when a sudden trauma causes brain damage. ... Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ...

See also

• Glutathione synthetase deficiency

Glutathione synthetase deficiency is a rare is a disorder that prevents the production of glutathione. ...

References

1. ^ Strużńka L, Chalimoniuk M, Sulkowski G. (September 2005). "The role of astroglia in Pb-exposed adult rat brain with respect to glutamate toxicity". Toxicology 212 (2-3): 185-194. PMID 15955607. Retrieved on 2006-05-05. 
2. ^ Dalton, TP & et al. (2000), Biochem Biophys Res Commun. 279 (2): 324
3. ^ Yang Y, et al. (2002) J Biol Chem. 277(51):4944.
4. ^ Giordano G, et al. (2007) Toxicol Appl Pharmacol. 219(2-3):181.
5. ^ McConnachie LA, et al. (2007) Tox Sci Epub 21 June.
6. ^ Chen Y, et al. (2007) Hepatology 45:1118.
7. ^ (2002) "Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes". Genome biology 3. 
8. ^ Grill D, Tausz T, De Kok LJ (2001). Significance of glutathione in plant adaptation to the environment. Springer. ISBN 1402001789. 
9. ^ Witschi A, et. al. The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992;43(6):667-9
10. ^ Pereira C.F, de Oliveira C.R. (July 2000). "Oxidative glutamate toxicity involves mitochondrial dysfunction and perturbation of intracellular Ca2+ homeostasis". Neuroscience Research 37 (3): 227-236. doi:doi:10.1016/S0168-0102(00)00124-3. Retrieved on 2006-05-05. 

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Related research

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• Ophthalmic acid