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|
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 [Ritz01a]. 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-peroxide redox reactions.
Unification Links: EcoCyc:GLUT-REDOX-PWY
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
Anderson90a: 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
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. 2. A method for purifying heterodimers of Escherichia coli glutathione reductase." Biochemistry 31(5);1498-504. PMID: 1737009
Deonarain92a: 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
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
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
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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