The ascorbate-glutathione cycle, sometimes

Foyer A lobby is a room in a building used for entry from the outside. Sometimes referred to as a foyer, reception area or an entrance hall, it is often a large room or complex of rooms (in a theatre, opera house, concert hall, showroom, cinema, etc. ...

Halliwell Halliwell is a surname. It may refer to: People * Bryn Halliwell (born 1980), English football goalkeeper * Danny Halliwell (born 1981), rugby league footballer who played in the 2000s and 2010s * David Halliwell (1936–2006), British dramatis ...

- Asada pathway, is a

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...

that detoxifies

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), a

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

that is produced as a waste product in

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

. The cycle involves the

antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...

metabolites:

ascorbate Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) and ...

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, pero ...

and

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 ...

and the enzymes linking these metabolites. In the first step of this pathway, H₂O₂ is reduced to water by

ascorbate peroxidase Ascorbate peroxidase (or L-ascorbate peroxidase, APX) () is an enzyme that catalyzes the chemical reaction :L-ascorbate + H2O2 \rightleftharpoons dehydroascorbate + 2 H2O It is a member of the family of heme-containing peroxidases. Heme peroxi ...

(APX) using

(ASC) as the electron donor. The oxidized ascorbate (monodehydroascorbate, MDA) is regenerated by monodehydroascorbate reductase (MDAR). However, monodehydroascorbate is a

radical Radical may refer to: Politics and ideology Politics *Radical politics, the political intent of fundamental societal change *Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...

and if not rapidly reduced it disproportionates into ascorbate and

dehydroascorbate 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 ot ...

(DHA). Dehydroascorbate is reduced to ascorbate by dehydroascorbate reductase (DHAR) at the expense of GSH, yielding oxidized glutathione (

GSSG 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 NADPH. This reaction is catalyzed ...

). Finally

is reduced by

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 fo ...

(GR) using NADPH as the electron donor. Thus

and

are not consumed; the net

electron The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family, and are generally thought to be elementary particles because they have no kn ...

flow is from

to H₂ O₂. The reduction of dehydroascorbate may be non-enzymatic or catalysed by proteins with dehydroascorbate reductase activity, such as glutathione ''S''-transferase omega 1 or

glutaredoxins 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 ...

. In

plants Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...

, the glutathione-ascorbate cycle operates in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

plastids The plastid (Greek: πλαστός; plastós: formed, molded – plural plastids) is a membrane-bound organelle found in the cells of plants, algae, and some other eukaryotic organisms. They are considered to be intracellular endosymbiotic cyanobac ...

and

peroxisomes A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...

. Since glutathione, ascorbate and NADPH are present in high concentrations in plant cells it is assumed that the glutathione-ascorbate cycle plays a key role for H₂O₂ detoxification. Nevertheless, other enzymes (

peroxidases Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides. Functionality Peroxidases typically ca ...

) including

peroxiredoxins 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 ...

and

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, which use

thioredoxin Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by ''TXN'' and ''TXN2'' genes. Loss-of-func ...

s or

as reducing substrates, also contribute to H₂O₂ removal in plants.

References

{{DEFAULTSORT:Ascorbate-Glutathione Cycle Metabolism Free radicals Antioxidants

See also

References