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Glutathione disulfide (GSSG) is a
disulfide In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
derived from two
glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
molecules. In living cells, glutathione disulfide is reduced into two molecules of glutathione with reducing equivalents from the
coenzyme A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...
NADPH. This reaction is catalyzed by the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
glutathione reductase Glutathione reductase (GR) also known as glutathione-disulfide reductase (GSR) is an enzyme that in humans is encoded by the GSR gene. Glutathione reductase (EC 1.8.1.7) catalyzes the reduction of glutathione disulfide ( GSSG) to the sulfhydryl f ...
. Antioxidant enzymes, such as
glutathione peroxidase Glutathione peroxidase (GPx) () is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid h ...
s and
peroxiredoxin Peroxiredoxins (Prxs, ; HGNC root symbol ''PRDX'') are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells. The family members in humans are P ...
s, generate glutathione disulfide during the reduction of
peroxide In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen ...
s such as
hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%â ...
(H2O2) and organic hydroperoxides (ROOH): :2 GSH + ROOH → GSSG + ROH + H2O Other enzymes, such as
glutaredoxin Glutaredoxins (also known as Thioltransferase) are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. In humans this oxidation repair enzyme is also known to participate in many cellular functi ...
s, generate glutathione disulfide through thiol-disulfide exchange with protein
disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
s or other low molecular mass compounds, such as coenzyme A disulfide or
dehydroascorbic acid Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid (vitamin C). It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and othe ...
. :2 GSH + R-S-S-R → GSSG + 2 RSH The GSH:GSSG ratio is therefore an important
bioindicator A bioindicator is any species (an indicator species) or group of species whose function, population, or status can reveal the qualitative status of the environment. The most common indicator species are animals. For example, copepods and other sma ...
of cellular health, with a higher ratio signifying less oxidative stress in the organism. A lower ratio may even be indicative of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease.


Neuromodulator

GSSG, along with glutathione and ''S''-nitrosoglutathione (GSNO), have been found to bind to the glutamate recognition site of the
NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...
and AMPA receptors (via their γ-glutamyl moieties), and may be endogenous
neuromodulator Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second ...
s. At
millimolar Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solut ...
concentrations, they may also modulate the redox state of the NMDA receptor complex.


See also

*
Glutathione-ascorbate cycle The ascorbate-glutathione cycle, sometimes Foyer-Halliwell- Asada pathway, is a metabolic pathway that detoxifies hydrogen peroxide (H2O2), a reactive oxygen species that is produced as a waste product in metabolism. The cycle involves the antiox ...
* Antioxidant


References

{{DEFAULTSORT:Glutathione Disulfide Organic disulfides Excitatory amino acid receptor ligands Neurotransmitters