Glutathione
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| Surname | Glutathione | ||||||||||||||||||
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| Molecular formula | C 10 H 17 N 3 O 6 S | ||||||||||||||||||
| Brief description |
white solid |
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| properties | |||||||||||||||||||
| Molar mass | 307.33 g mol −1 | ||||||||||||||||||
| Physical state |
firmly |
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| Melting point |
185-195 ° C |
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| solubility |
soluble in water (100 g l −1 at 20 ° C) and dimethylformamide |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Glutathione ( GSH ), also γ- L -glutamyl- L -cysteinylglycine, is a tripeptide that is formed from the three amino acids glutamic acid , cysteine and glycine . It is found in high concentrations in almost all cells and is one of the most important antioxidant substances in the body. At the same time it is a reserve for cysteine. Glutathione is not a true tripeptide because the amide bond between glutamic acid and cysteine is formed via the γ-carboxy group of glutamic acid and not via the α-carboxy group as in a real peptide bond.
Actinobacteria produce mycothiol instead of glutathione.
biosynthesis
Glutathione can be synthesized by the body from the amino acids L - glutamic acid , L - cysteine and glycine in a two-step process.
- With ATP consumption, γ-glutamylcysteine is formed from glutamic acid and cysteine . An ω-peptide bond is formed between the γ- carboxy group of the glutamic acid residue and the amino group of the cysteine residue. The enzyme involved is called glutamate cysteine ligase (GCL, also γ-glutamylcysteine synthetase).
- With the help of glutathione synthase , glycine is added to the terminal carbon atom while consuming ATP.
All cells in the human body have the ability to synthesize GSH. The biosynthesis of the substance in the liver is essential: Mice with impaired glutathione production in the liver die within one month of birth.
Most eukaryotes are capable of GSH synthesis, but not Entamoeba and Giardia . The biosynthetic pathway occurs in some bacteria, such as B. cyanobacteria and proteobacteria , but many other bacteria are absent. Among the archaea , only halobacteria can synthesize GSH.
function
Cysteine reserve
GSH is best known as the main substance in the reductive pool. A constant supply of cysteine is essential for protein synthesis, but cysteine is reactive and is constantly irreversibly lost in an aerobic environment through oxidation to cysteine sulfinic and sulfonic acid. GSH thus also represents an emergency reserve for the amino acid cysteine. It is also used for taurine synthesis .
The human blood plasma contains around three grams of cysteine in the form of GSH, which corresponds to a reserve for three days.
Redox buffer
GSH can help protect cellular macromolecules, such as proteins and membrane lipids, from “ free radicals ” (reactive oxygen species, ROS). Glutathione is oxidized and changes from its monomeric form GSH to a dimer GSSG.
ROS, which in the course of cell respiration can occur, pose a significant threat to many cellular components represent. Reduced glutathione (GSH) has a free thiol group and can thus in turn electrons to ROS transfer and make them harmless. Two oxidized glutathione molecules combine to form a glutathione disulfide (GSSG) , forming a disulfide bridge . The enzyme glutathione reductase can be used to produce two reduced GSH from one GSSG dimer while consuming NADPH . The redox potential of GSH is −240 mV and is 90% reduced due to the activity of glutathione reductase.
Biotransformation
GSH plays an important role in phase II of the biotransformation of harmful substances. Substances conjugated with GSH are usually more soluble in water and can be eliminated via the kidneys . The glutathione-S-transferase , which is mostly localized in the cytosol , catalyzes the reaction of GSH with electrophilic carbon. Here can Halogen -, sulfate -, sulfonate -, phosphate - and nitro groups by glutathione substituted are. Furthermore, GSH can be added to activated double bonds and open reactive epoxy rings . The toxic (poisonous) effect includes the activation of vicinal dihaloalkanes with the formation of a highly reactive episulfonium ring as well as a β-lyase-mediated conversion of the GSH conjugates in the kidney to reactive compounds.
More functions
In plants, nematodes, algae and fungi, glutathione also serves as a substrate for the synthesis of phytochelatins , which, like metallothioneins, play an important role in binding heavy metals .
Glutathione fulfills another task in the synthesis of certain leukotrienes, for example in the synthesis of leukotriene C4 . Leukotriene A4 is converted into leukotriene C4 with the help of glutathione-S-transferase.
history
When Frederick Gowland Hopkins described a cysteine-containing peptide in yeast and animal cells in 1921 and named it glutathione, it was initially thought that it was γ-glutamylcysteine. Only Harington and Mead were able to confirm the later assumed actual structure by total synthesis in 1935.
Food supplements
Because of its antioxidant properties, glutathione is sold as a dietary supplement . The bioavailability of dietary glutathione is generally estimated to be very low, but was evaluated in April 2013 by a Penn State College study of 54 students with positive results. Parenteral delivery increases the level of GSH in the cells. A potential health benefits glutathione, for example as anti-cancer agents or as agents in the age inhibition , has yet to be scientifically proven in clinical trials. A stimulation of glutathione production in the liver by the administration of acetylcysteine (as a cysteine donor ) is associated with possible health risks in healthy control persons in an EFSA opinion from 2004.
As a controversial "cancer drug", glutathione was used as a mixture with anthocyanins under the name Recancostat comp. sold preparation in the mid-1990s.
literature
- Ashley Wilber (Ed.): Glutathione: Dietary Sources, Role in Cellular Functions and Therapeutic Effects. Nova Science Publishers, New York 2015, ISBN 978-1-63463-372-7 .
Web links
Individual evidence
- ↑ a b c data sheet glutathione (PDF) from Merck , accessed on December 14, 2010.
- ↑ Entry on glutathione. In: Römpp Online . Georg Thieme Verlag, accessed on May 5, 2011.
- ↑ a b c data sheet glutathione from Sigma-Aldrich , accessed on February 13, 2019 ( PDF ).
- ↑ Y. Chen et al. a .: Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure. In: Hepatology . 45, 2007, p. 1118.
- ↑ David Heber, George L. Blackburn, Vay Liang W. Go, John Milner (Eds.): Nutritional Oncology. Academic Press, 2006, ISBN 0-12-088393-7 , p. 310.
- ↑ F. Aslund, KD Berndt, A. Holmgren: Redox potentials of glutaredoxins and other thiol-disulfide oxidoreductases of the thioredoxin superfamily determined by direct protein-protein redox equilibria. In: J Biol Chem . 272 (49), 1997, pp. 30780-30786. PMID 9388218 .
- ↑ FG Hopkins: On an autoxidizable constituent of the cell. In: Biochem J. 15, 1921, pp. 286-305. biochemj.org
- ↑ CR Harington, TH Mead: Synthesis of glutathione . In: Biochem. J. Band 29 , no. 7 July 1935, p. 1602-1611 , PMID 16745829 , PMC 1266669 (free full text) - ( biochemj.org ).
- ↑ Markus Minoggio: What the body really needs ...: Via dietary supplements, vitamins and pseudo-products . Goldegg Verlag, 2008, ISBN 978-3-901880-16-2 , p. 194.
- ↑ Research shows oral supplement increases body's storage of antioxidant . In: Penn State News. April 22, 2013.
- ↑ Glutathione News (German translation of the Penn State Study): Clinical tests prove the long-term effectiveness of orally administered glutathione as a dietary supplement ( Memento from February 22, 2014 in the Internet Archive )
- ↑ MK Robinson, MS Ahn, JD Rounds, JA Cook, DO Jacobs, DW Wilmore: Parenteral glutathione monoester enhances tissue antioxidant stores. In: JPEN J Parenter Enteral Nutr. 16 (5), Sep-Oct 1992, pp. 413-418.
- ↑ Ben Pfeifer, Joachim Preiß, Clemens Unger (eds.): Oncology integrative: conventional and complementary therapy. Urban & Fischer Verlag / Elsevier, 2006, ISBN 3-437-56420-X , pp. 357-358.
- ↑ Glutathione News: Reduced Glutathione (GSH) or GSH precursors such as N-acetylcysteine (NAC)? ( Memento from February 10, 2013 in the Internet Archive )
- ↑ N-acetyl-L-cysteine for use in foods for special nutritional purposes and in foods for special medical purposes . (PDF) EFSA opinion
- ↑ Reimbursement of pharmaceuticals, concept of finished pharmaceuticals . ( Memento of March 4, 2009 in the Internet Archive ) LSG Lower Saxony-Bremen, judgment of February 15, 2005, Az .: L 4 KR 44/01. arzneimittel-und-recht.de; Retrieved May 10, 2010.