MetaCyc Pathway: ascorbate glutathione cycle
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: ascorbate glutathione cycle

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: hydrogen peroxide detoxification

Superclasses: Detoxification

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Brassica rapa, Cucumis sativus, Cucurbita pepo medullosa , Euglena, Pisum sativum, Solanum tuberosum, Spinacia oleracea

Expected Taxonomic Range: Cyanobacteria, Euglenozoa, Viridiplantae

Many metabolic processes, including respiration, photosynthetic electron transport and oxidation of glycolate in photorespiration, generate reactive oxygen species such as singleton oxygen and hydrogen peroxide. For example, the univalent reduction of dioxygen in illuminated chloroplasts produces superoxide anion radicals, which are disproportionate to hydrogen peroxide and dioxygen by the superoxide dismutase enzyme, contained in the stroma and lumen. These highly reactive compounds can damage membrane lipids and certain enzymes and thus interrupt cell function.

The ascorbate-glutathione cycle performs the scavenging of hydrogen peroxide. In this cycle, L-ascorbate and glutathione transfer reducing power from NADPH to hydrogen peroxide, reducing it to water. The reduction of hydrogen peroxide is catalyzed by L-ascorbate peroxidase (cytosolic), in a reaction that generates monodehydroascorbate radical, a radical that can be reduced to ascorbate by monodehydroascorbate reductase. If not reduced rapidly, monodehydroascorbate is disproportionated into L-ascorbate and L-dehydro-ascorbate, and the latter is reduced back to L-ascorbate by dehydroascorbate reductase using glutathione as the reducing agent. The oxidized glutathione is reduced by glutathione reductase using NADPH (see glutathione-glutaredoxin redox reactions).

The ascorbate-glutathione cycle presents in at least four different subcellular locations including the cytosol, chloroplast, mitochondrion and peroxisome. Studies of the Arabidopsis enzymes of the pathway show that the same set of enzymes, including L-ascorbate peroxidase (cytosolic), monodehydroascorbate reductase and glutathione reductase, are dual targeted to chloroplast and mitochondrion [Chew03]. Ascorbate peroxidase is in fact the major peroxidase in spinach leaves.

A similar scavenging system appears to operate in several species of cyanobacteria and Euglena.

Citations: [Jimenez97, Shigeoka02]

Unification Links: AraCyc:PWY-2261


Chew03: Chew O, Whelan J, Millar AH (2003). "Molecular definition of the ascorbate-glutathione cycle in Arabidopsis mitochondria reveals dual targeting of antioxidant defenses in plants." J Biol Chem 278(47);46869-77. PMID: 12954611

Jimenez97: Jimenez A, Hernandez JA, Del Rio LA, Sevilla F (1997). "Evidence for the Presence of the Ascorbate-Glutathione Cycle in Mitochondria and Peroxisomes of Pea Leaves." Plant Physiol 114(1);275-284. PMID: 12223704

Noctor98a: Noctor G, Foyer CH (1998). "ASCORBATE AND GLUTATHIONE: Keeping Active Oxygen Under Control." Annu Rev Plant Physiol Plant Mol Biol 49;249-279. PMID: 15012235

Shigeoka02: Shigeoka S, Ishikawa T, Tamoi M, Miyagawa Y, Takeda T, Yabuta Y, Yoshimura K (2002). "Regulation and function of ascorbate peroxidase isoenzymes." J Exp Bot 53(372);1305-19. PMID: 11997377

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Board00: Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Kamath AV, Rosner MH, Chrunyk BA, Perregaux DE, Gabel CA, Geoghegan KF, Pandit J (2000). "Identification, characterization, and crystal structure of the Omega class glutathione transferases." J Biol Chem 275(32);24798-806. PMID: 10783391

DiLabio00: DiLabio GA, Wright JS (2000). "Hemiketal formation of dehydroascorbic acid drives ascorbyl radical anion disproportionation." Free Radic Biol Med 29(5);480-5. PMID: 11020669

Green05: Green MA, Fry SC (2005). "Vitamin C degradation in plant cells via enzymatic hydrolysis of 4-O-oxalyl-L-threonate." Nature 433(7021);83-7. PMID: 15608627

Ishikawa96: Ishikawa T, Sakai K, Yoshimura K, Takeda T, Shigeoka S (1996). "cDNAs encoding spinach stromal and thylakoid-bound ascorbate peroxidase, differing in the presence or absence of their 3'-coding regions." FEBS Lett 384(3);289-93. PMID: 8617374

Ishikawa96a: Ishikawa, Takahiro, Takeda, Toru, Shigeoka, Shigeru "Purification and characterization of cytosolic ascorbate peroxidase from komatsuna (Brassica rapa)." Plant Science, 1996, 120:11-18.

Ishikawa98a: Ishikawa T, Yoshimura K, Sakai K, Tamoi M, Takeda T, Shigeoka S (1998). "Molecular characterization and physiological role of a glyoxysome-bound ascorbate peroxidase from spinach." Plant Cell Physiol 39(1);23-34. PMID: 9516999

Kerber08: Kerber, R. C. (2008). ""As simple as possible, but not simpler" - the case of dehydroascorbic acid." J. Chem. Ed. 85(9):1237-1242.

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Leonardis00: Leonardis, Silvana, Dipierro, Nunzio, Dipierro, Silvio "Purification and characterization of an ascorbate peroxidase from potato tuber mitochondria." Plant Physiology and Biochemistry, 2000, 38(10):773-779.

Linster07: Linster CL, Van Schaftingen E (2007). "Vitamin C. Biosynthesis, recycling and degradation in mammals." FEBS J 274(1);1-22. PMID: 17222174

Macdonald06: Macdonald IK, Badyal SK, Ghamsari L, Moody PC, Raven EL (2006). "Interaction of ascorbate peroxidase with substrates: a mechanistic and structural analysis." Biochemistry 45(25);7808-17. PMID: 16784232

May98: May JM, Cobb CE, Mendiratta S, Hill KE, Burk RF (1998). "Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase." J Biol Chem 273(36);23039-45. PMID: 9722529

Murthy94: Murthy SS, Zilinskas BA (1994). "Molecular cloning and characterization of a cDNA encoding pea monodehydroascorbate reductase." J Biol Chem 269(49);31129-33. PMID: 7983054

Nakano87: Nakano, Y, Asada, K. (1987). "Purification of Ascorbate Peroxidase in Spinach Chloroplasts; Its Inactivation in Ascorbate-Depleted Medium and Reactivation by Monodehydroascorbate Radical." Pl. Cell Physiol. 28:131-140.

Patterson95: Patterson WR, Poulos TL (1995). "Crystal structure of recombinant pea cytosolic ascorbate peroxidase." Biochemistry 34(13);4331-41. PMID: 7703247

Sano95: Sano S, Miyake C, Mikami B, Asada K (1995). "Molecular characterization of monodehydroascorbate radical reductase from cucumber highly expressed in Escherichia coli." J Biol Chem 270(36);21354-61. PMID: 7545669

Sharp04: Sharp KH, Moody PC, Brown KA, Raven EL (2004). "Crystal structure of the ascorbate peroxidase-salicylhydroxamic acid complex." Biochemistry 43(27);8644-51. PMID: 15236572

Shigeoka80: Shigeoka S, Nakano Y, Kitaoka S (1980). "Metabolism of hydrogen peroxide in Euglena gracilis Z by L-ascorbic acid peroxidase." Biochem J 186(1);377-80. PMID: 6768357

Shigeoka80a: Shigeoka S, Nakano Y, Kitaoka S (1980). "Purification and some properties of L-ascorbic-acid-specific peroxidase in Euglena gracilis Z." Arch Biochem Biophys 201(1);121-7. PMID: 6772104

Shimaoka00: Shimaoka T, Yokota A, Miyake C (2000). "Purification and characterization of chloroplast dehydroascorbate reductase from spinach leaves." Plant Cell Physiol 41(10);1110-8. PMID: 11148269

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 20.0 (software by SRI International) on Fri May 6, 2016, BIOCYC12.