Glutathione disulfide (GSSG) is a disulfide derived from two glutathione 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 Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...

. 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. A ...

glutathione reductase. Antioxidant enzymes, such as glutathione peroxidases 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 PRDX ...

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 p ...

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%� ...

(H₂O₂) and

organic hydroperoxide In organic chemistry, organic peroxides are organic compounds containing the peroxide functional group (). If the R′ is hydrogen, the compounds are called hydroperoxides, which are discussed in that article. The O−O bond of peroxides easily b ...

s (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 bonds or other low molecular mass compounds, such as

coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...

disulfide or dehydroascorbic acid. :2 GSH + R-S-S-R → GSSG + 2 RSH The GSH:GSSG ratio is therefore an important bioindicator 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 Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

Neuromodulator

GSSG, along with glutathione and ''S''-nitrosoglutathione (GSNO), have been found to bind to the

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

recognition site of the NMDA and

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...

s (via their γ-glutamyl moieties), and may be

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

neuromodulators. At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex.

References

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

Neuromodulator

See also

References