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MetaCyc Pathway: glutathione redox reactions II

Enzyme View:

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.

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Reductants Biosynthesis

Some taxa known to possess this pathway include ? : Escherichia coli K-12 substr. MG1655 , Homo sapiens , Pisum sativum

Expected Taxonomic Range: Bacteria , Eukaryota

Summary:
General Background

Thiols play several major roles in the cell; they help maintain the redox balance, keep a reduced environment, fight reactive oxygen and nitrogen species, and they are involved in the detoxification of many other toxins and stress-inducing factors (see glutathione-mediated detoxification I). In most organisms, the major thiol is the tripeptide glutathione (γ-Glu-Cys-Gly, known as GSH), whose intracellular concentration ranges from 0.5-10 mM (see γ-glutamyl cycle).

Most of the glutathione pool is kept in its reduced form. For example, in Escherichia coli, the ratio of reduced to oxidized glutathione is 200:1 [Ritz01]. The functionality of GSH largely depends on its being in a reduced form.

About This Pathway

Oxidative damage to proteins often results in the formation of mixed disulfides within the polypetides. A primary defense against this damage is mediated by the action of GSH-dependent thiol-disulfide oxidoreductases, also called thioltransferases and best known as glutaredoxins (Grx). These proteins reduce the protein disulfide groups back to their native form [Luikenhuis98] (an example for these proteins is reduced glutaredoxin 1 from Escherichia coli).

The glutaredoxins, which are oxidized during this process, are reduced back to active form with electrons that are donated by reduced GSH molecules. In this reaction, two molecules of the reduced form GSH are oxidized, condensing into the single molecule glutathione disulfide. The disulfide is reduced back into two individual GSH molecules by the action of the enzyme glutathione reductase.

Another redox cycle involving glutathione, which is found in eukaryotic organisms, is described in glutathione redox reactions I.

Unification Links: EcoCyc:GLUT-REDOX-PWY

Credits:
Created 04-Apr-1996 by Riley M , Marine Biological Laboratory
Revised 15-Jul-2005 by Caspi R , SRI International


References

Luikenhuis98: Luikenhuis S, Perrone G, Dawes IW, Grant CM (1998). "The yeast Saccharomyces cerevisiae contains two glutaredoxin genes that are required for protection against reactive oxygen species." Mol Biol Cell 9(5);1081-91. PMID: 9571241

Ritz01: Ritz D, Beckwith J (2001). "Roles of thiol-redox pathways in bacteria." Annu Rev Microbiol 55;21-48. PMID: 11544348

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

Anderson90: Anderson, James, Hess, John, Chevone, Boris "Purification, characterization, and immunological properties of two isoforms of glutathione reductase from Eastern white pine needles." Plant Physiology, 1990, 94:1402-1409.

Arscott89: Arscott LD, Drake DM, Williams CH (1989). "Inactivation-reactivation of two-electron reduced Escherichia coli glutathione reductase involving a dimer-monomer equilibrium." Biochemistry 28(8);3591-8. PMID: 2663073

BeckerHapak95: Becker-Hapak M, Eisenstark A (1995). "Role of rpoS in the regulation of glutathione oxidoreductase (gor) in Escherichia coli." FEMS Microbiol Lett 134(1);39-44. PMID: 8593953

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Davis82: Davis NK, Greer S, Jones-Mortimer MC, Perham RN (1982). "Isolation and mapping of glutathione reductase-negative mutants of Escherichia coli K12." J Gen Microbiol 128(7);1631-4. PMID: 6214613

Deonarain89: Deonarain MP, Berry A, Scrutton NS, Perham RN (1989). "Alternative proton donors/acceptors in the catalytic mechanism of the glutathione reductase of Escherichia coli: the role of histidine-439 and tyrosine-99." Biochemistry 28(25);9602-7. PMID: 2558727

Deonarain90: Deonarain MP, Scrutton NS, Berry A, Perham RN (1990). "Directed mutagenesis of the redox-active disulphide bridge in glutathione reductase from Escherichia coli." Proc R Soc Lond B Biol Sci 1990;241(1302);179-86. PMID: 1979442

Deonarain92: Deonarain MP, Scrutton NS, Perham RN (1992). "Engineering surface charge. 1. A method for detecting subunit exchange in Escherichia coli glutathione reductase." Biochemistry 31(5);1491-7. PMID: 1737008

Deonarain92a: Deonarain MP, Scrutton NS, Perham RN (1992). "Engineering surface charge. 2. A method for purifying heterodimers of Escherichia coli glutathione reductase." Biochemistry 31(5);1498-504. PMID: 1737009

Edwards90: Edwards, E. Anne, Rawsthorne, Stephen, Mullineaux, Philip M. "Subcellular distribution of multiple forms of glutathione reductase in leaves of pea." Planta, 1990, 180:278-284.

Ermler91: Ermler U, Schulz GE (1991). "The three-dimensional structure of glutathione reductase from Escherichia coli at 3.0 A resolution." Proteins 9(3);174-9. PMID: 2006135

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Greer86: Greer S, Perham RN (1986). "Glutathione reductase from Escherichia coli: cloning and sequence analysis of the gene and relationship to other flavoprotein disulfide oxidoreductases." Biochemistry 25(9);2736-42. PMID: 3521741

Helmward89: Helmward Z "Handbook of Enzyme Inhibitors. 2nd, revised and enlarged edition." Weinheim, Federal Republic of Germany ; New York, NY, USA , 1989.

Henderson91: Henderson GB, Murgolo NJ, Kuriyan J, Osapay K, Kominos D, Berry A, Scrutton NS, Hinchliffe NW, Perham RN, Cerami A (1991). "Engineering the substrate specificity of glutathione reductase toward that of trypanothione reduction." Proc Natl Acad Sci U S A 88(19);8769-73. PMID: 1924337

Holmgren76: Holmgren A (1976). "Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione." Proc Natl Acad Sci U S A 1976;73(7);2275-9. PMID: 7783

Knapp04: Knapp KG, Swartz JR (2004). "Cell-free production of active E. coli thioredoxin reductase and glutathione reductase." FEBS Lett 559(1-3);66-70. PMID: 14960309

KrohneEhrich77: Krohne-Ehrich G, Schirmer RH, Untucht-Grau R (1977). "Glutathione reductase from human erythrocytes. Isolation of the enzyme and sequence analysis of the redox-active peptide." Eur J Biochem 80(1);65-71. PMID: 923580

Kunert90: Kunert KJ, Cresswell CF, Schmidt A, Mullineaux PM, Foyer CH (1990). "Variations in the activity of glutathione reductase and the cellular glutathione content in relation to sensitivity to methylviologen in Escherichia coli." Arch Biochem Biophys 1990;282(2);233-8. PMID: 2241146

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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 SRI International Pathway Tools version 18.5 on Wed Nov 26, 2014, BIOCYC14B.