Glutathione

• 2-amino -5- { [1 - ( (carboxymethyl ) amino )-1- oxo-3- sulfanylprop -2-yl ] amino} -5- oxovaleric acid
• γ -L-glutamyl -L- cysteinyl -glycine
• GSH

White solid

Fixed

185-195 ° C

Soluble in water (100 g · l-1 at 20 ° C ) and dimethylformamide

5000 mg · kg -1 ( LD50, mouse, oral)

Template: Infobox chemical / molecular formula search available

Glutathione (GSH), and γ -L-glutamyl -L- cysteinylglycine, is a tripeptide formed from the three amino acids glutamic acid, cysteine ​​and glycine. It is found in almost all cells in a high concentration and one of the main acting as an antioxidant substances in the body. At the same time, it is a reserve for cysteine. It is not a real on glutathione tripeptide, as the amide bond between glutamic acid and cysteine, is formed on the γ - carboxyl group of the glutamic acid, and not on the α -carboxyl group as a true 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.

• Consumption of ATP is formed from glutamic acid and cysteine ​​γ -glutamylcysteine ​​. This one isopeptide bond between the γ - carboxyl group of glutamic acid with the amino group of the cysteine ​​residue is formed. The parties engaged in these enzyme called Glutamatcysteinligase ( GCL, also γ - glutamylcysteine ​​synthetase ).
• With the help of Glutathionsynthase glycine is added to the terminal carbon atom with ATP consumption.

All the cells of the human body possess the capability to synthesize GSH. The biosynthesis of the substance is essential in the liver: mice with impaired glutathione in the liver die within a month after birth.

Most eukaryotes are capable of GSH synthesis, but not as Entamoeba and Giardia. The biosynthetic pathway is expressed in some bacteria from, for example cyanobacteria and Proteobacteria, but lacking many other bacteria. Among the archaea only Halo bacteria themselves can synthesize GSH.

Function

Cysteine ​​Reserve

Best known as GSH is the main substance of the reductive pools. A constant supply of cysteine ​​is essential for protein synthesis, but cysteine ​​is reactive and is constantly in an aerobic environment irreversibly lost by oxidation to Cysteinsulfin and acid. GSH therefore also provides an emergency reserve of the amino acid cysteine ​​dar. It is also used to Taurinsynthese.

In human blood plasma for about three grams of cysteine ​​in the form of GSH are contained, which corresponds to a reserve for three days.

Redox buffer

GSH may help protect cellular macromolecules, such as proteins and membrane lipids of "free radicals" (reactive oxygen species, ROS). This glutathione is oxidized and goes from its monomeric form GSH in a dimer GSSG over.

ROS that may arise in the course of cellular respiration, pose a significant threat to many cellular components dar. Reduced glutathione ( GSH ) has a free thiol group and can thus in turn transfer electrons to ROS and make them as harmless. Two oxidized glutathione molecules combine to form a disulfide bridge to a glutathione disulfide (GSSG ). By the enzyme glutathione reductase can be produced from a dimer, GSSG with consumption of NADPH again two reduced GSH. The redox potential of -240 mV is GSH, and is through the activity of glutathione reductase before reduced to 90%.

Biotransformation

GSH plays an important role in phase II biotransformation of harmful substances. With GSH conjugated substances are usually more water soluble and can be excreted through the kidneys. The mostly localized in the cytosol glutathione S- transferase catalyzes the reaction of GSH with electrophilic carbon. In this case, halogen, sulfate, sulfonate, phosphate and nitro groups can be substituted by glutathione. Furthermore, GSH is added to activated double bonds and open reactive epoxide. The toxifizierende ( toxic ) effect involves activation of vicinal dihaloalkanes to form a highly reactive Episulfoniumringes and a β - lyase mediated conversion of GSH conjugates in the kidney to reactive compounds.

Other Features

In plants, nematodes, algae and fungi which also serves as a substrate for glutathione synthesis phytochelatins, which play an important role as metallothioneins in the binding of heavy metals.

A further object satisfied glutathione in the synthesis of certain leukotrienes, such as in the synthesis of leukotriene C4. Of leukotriene A4 formed by using the glutathione -S-transferase leukotriene C4.

History

As Frederick Gowland Hopkins 1921 cysteinhaltiges peptide in yeast and animal cells, described and named glutathione, we considered first, if it were γ -glutamylcysteine ​​. Only Harington and Mead were able to confirm the suspected actual structure later in 1935 by total synthesis.

Dietary supplements

Due to its antioxidant action, glutathione is sold as a dietary supplement. The therapeutic benefit of on the food supplied glutathione was clearly demonstrated by a study conducted by the Penn State College in April 2013. Parenteral feeding increases GSH levels 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 studies. Stimulation of glutathione in the liver by administration of acetylcysteine ​​(as Cysteindonor ) into an opinion of EFSA with possible health risks in healthy control persons in connection.

As controversial " cancer drug " achieved glutathione in a mixture with anthocyanins under the name Recancostat comp. preparation sold mid-1990s fame.