Glutathione reductase

Last updated
GSR
Glutathione reductase.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GSR , HEL-75, HEL-S-122m, glutathione reductase, glutathione-disulfide reductase, GR, GSRD
External IDs OMIM: 138300 MGI: 95804 HomoloGene: 531 GeneCards: GSR
Orthologs
SpeciesHumanMouse
Entrez

2936

14782

Ensembl

ENSG00000104687

ENSMUSG00000031584

UniProt

P00390

P47791

RefSeq (mRNA)

NM_001195104
NM_000637
NM_001195102
NM_001195103

NM_010344

RefSeq (protein)

NP_000628
NP_001182031
NP_001182032
NP_001182033

NP_034474

Location (UCSC) Chr 8: 30.68 – 30.73 Mb Chr 8: 34.14 – 34.19 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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 form glutathione (GSH), which is a critical molecule in resisting oxidative stress and maintaining the reducing environment of the cell. [5] [6] [7] Glutathione reductase functions as dimeric disulfide oxidoreductase and utilizes an FAD prosthetic group and NADPH to reduce one molar equivalent of GSSG to two molar equivalents of GSH:

General reaction catalyzed by glutathione reductase GSR Scheme 1.PNG
General reaction catalyzed by glutathione reductase

The glutathione reductase is conserved between all kingdoms. In bacteria, yeasts, and animals, one glutathione reductase gene is found; however, in plant genomes, two GR genes are encoded. Drosophila and trypanosomes do not have any GR at all. [8] In these organisms, glutathione reduction is performed by either the thioredoxin or the trypanothione system, respectively. [8] [9]

Function

glutathione-disulfide reductase
GSR Model Figure.PNG
Human GSR with bound glutathione and FADH
Identifiers
EC no. 1.8.1.7
CAS no. 9001-48-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins

Glutathione plays a key role in maintaining proper function and preventing oxidative stress in human cells. It can act as a scavenger for hydroxyl radicals, singlet oxygen, and various electrophiles. Reduced glutathione reduces the oxidized form of the enzyme glutathione peroxidase, which in turn reduces hydrogen peroxide (H2O2), a dangerously reactive species within the cell. [In the following illustration of redox reeactions, the rightmost arrow is reversed; it should be pointing up not down.] In addition, it plays a key role in the metabolism and clearance of xenobiotics, acts as a cofactor in certain detoxifying enzymes, participates in transport, and regenerates antioxidants such and Vitamins E and C to their reactive forms. The ratio of GSSG/GSH present in the cell is a key factor in properly maintaining the oxidative balance of the cell, that is, it is critical that the cell maintains high levels of the reduced glutathione and a low level of the oxidized glutathione disulfide. This narrow balance is maintained by glutathione reductase, which catalyzes the reduction of GSSG to GSH. [5]

Reduced glutathione reductase, glutathione peroxidase and glutathione interact to reduce hydrogen peroxide to water, in order to protect the cell from oxidative damage. Gluthathione Reductase Graphic 7.jpg
Reduced glutathione reductase, glutathione peroxidase and glutathione interact to reduce hydrogen peroxide to water, in order to protect the cell from oxidative damage.

Structure


Glutathione reductase from human erythrocytes is a homodimer consisting of 52Kd monomers, each containing 3 domains. GR exhibits single sheet, double layered topology where an anti-parallel beta-sheet is largely exposed to the solvent on one face while being covered by random coils on the other face. [10] This includes and NADPH-binding Domain, FAD-binding domain(s) and a dimerization domain. Each monomer contains 478 residues and one FAD molecule. GR is a thermostable protein, retaining function up to 65 °C. [11] [12]

Reaction mechanism

Graphical representation of overall reaction catalyzed by GR GSR Reaction Figure.PNG
Graphical representation of overall reaction catalyzed by GR
GR catalytic cycle GSR Catalytic Cycle.PNG
GR catalytic cycle

Steps:

1NADPH binding to the oxidized enzyme
2Reduction of FAD to FADH− anion by NADPH
3Reduced FADH− anion collapses into a charge relay complex and reduces Cys58-Cys63 disulfide
4Oxidized Glutathione disulfide binds to the reduced enzyme and forms a mixed disulfide with Cys58 and releases one reduced glutathione
5Cys63 attacks the mixed disulfide on Cys58 to release a reduced glutathione and reform the redox active disulfide

Reductive half

The action of GR proceeds through two distinct half reactions, a reductive half mechanism followed by an oxidative half. In the first half, NADPH reduces FAD present in GSR to produce a transient FADH− anion. This anion then quickly breaks a disulfide bond of Cys58 - Cys63, forming a short lived covalent bond a stable charge-transfer complex between the flavin and Cys63. The now oxidized NADP+ is released and is subsequently replaced by a new molecule of NADPH. This is the end of the so-called reductive half of the mechanism.

Oxidative half

In the oxidative half of the mechanism, Cys63 nucleophilically attacks the nearest sulfide unit in the GSSG molecule (promoted by His467), which creates a mixed disulfide bond (GS-Cys58) and a GS− anion. His467 of GSR then protonates the GS- anion to release the first molecule of GSH. Next, Cys63 nucleophilically attacks the sulfide of Cys58, releasing a GS− anion, which, in turn, picks up a solvent proton and is released from the enzyme, thereby creating the second GSH. So, for every GSSG and NADPH, two reduced GSH molecules are gained, which can again act as antioxidants scavenging reactive oxygen species in the cell. [13]

Inhibition

In vitro, glutathione reductase is inhibited by low concentrations of sodium arsenite and methylated arsenate metabolites, but in vivo, significant Glutathione Reductase inhibition by sodium arsenate has only been at 10 mg/kg/day. [14] Glutathione reductase is also inhibited by some flavanoids, a class of pigments produced by plants. [15]

Clinical significance

GSH is a key cellular antioxidant and plays a major role in the phase 2 metabolic clearance of electrophilic xenobiotics. The importance of the GSH pathway and enzymes that affect this delicate balance is gaining an increased level of attention in recent years. Although glutathione reductase has been an attractive target for many pharmaceuticals, there have been no successful glutathione reductase related therapeutic compounds created to date. In particular, glutathione reductase appears to be a good target for anti-malarials, as the glutathione reductase of the malaria parasite Plasmodium falciparum has a significantly different protein fold than that of mammalian glutathione reductase. [16] By designing drugs specific to p. falciparum it may be possible to selectively induce oxidative stress in the parasite, while not affecting the host.

There are two main classes of GR targeting compounds: [17] [18] [19] [20]

  1. Inhibitors of GSSG binding, or dimerization: Reactive electrophiles such as gold compounds, and fluoronaphthoquinones.
  2. Drugs which use glutathione reductase to regenerate, such as redox cyclers. Two examples of these types of compounds are Methylene blue and Naphthoquinone.

Clinical trials performed in Burkina Faso have revealed mixed results when treating malaria with Naphthoquinones

In cells exposed to high levels of oxidative stress, like red blood cells, up to 10% of the glucose consumption may be directed to the pentose phosphate pathway (PPP) for production of the NADPH needed for this reaction. In the case of erythrocytes, if the PPP is non-functional, then the oxidative stress in the cell will lead to cell lysis and anemia. [21]

Lupus is an autoimmune disorder in which patients produce an elevated quantity of antibodies that attack DNA and other cell components. In a recent study, a single nucleotide polymorphism (SNP) in the Glutathione Reductase gene was found to be highly associated with lupus in African Americans in the study. [22] African Americans with lupus have also been shown to express less reduced glutathione in their T cells. [23] The study's authors believe that reduced glutathione reductase activity may contribute to the increased production of reactive oxygen in African Americans with lupus. [22]

In mice, glutathione reductase has been implicated in the oxidative burst, a component of the immune response. [24] The oxidative burst is a defense mechanism in which neutrophils produce and release reactive oxidative species in the vicinity of bacteria or fungi to destroy the foreign cells. Glutathione Reductase deficient neutrophils were shown to produce a more transient oxidative burst in response to bacteria than neutrophils that express GR at ordinary levels. [24] The mechanism of Glutathione Reductase in sustaining the oxidative burst is still unknown. [24]

Deficiency

Glutathione reductase deficiency is a rare disorder in which the glutathione reductase activity is absent from erythrocytes, leukocytes or both. In one study this disorder was observed in only two cases in 15,000 tests for glutathione reductase deficiency performed over the course of 30 years. [25] In the same study, glutathione reductase deficiency was associated with cataracts and favism in one patient and their family, and with severe unconjugated hyperbilirubinemia in another patient. [25] It has been proposed that the glutathione redox system (of which glutathione reductase is a part) is almost exclusively responsible for the protecting of eye lens cells from hydrogen peroxide because these cells are deficient in catalase, an enzyme which catalyzes the breakdown of hydrogen peroxide, and the high rate of cataract incidence in glutathione reductase deficient individuals. [26]

Some patients exhibit deficient levels of glutathione activity as a result of not consuming enough riboflavin in their diets. Riboflavin is a precursor for FAD, whose reduced form donates two electron to the disulfide bond which is present in the oxidized form of glutathione reductase in order to begin the enzyme's catalytic cycle. In 1999, a study found that 17.8% of males and 22.4% of females examined in Saudi Arabia suffered from low glutathione reductase activity due to riboflavin deficiency. [27]

Connection to favism

In favism, patients lack glucose-6-phosphate dehydrogenase, an enzyme in their pentose phosphate pathway that reduces NADP+ to NADPH while catalyzing the conversion of glucose-6-phosphate to 6-phosphoglucono-δ-lactone. Glucose-6-phosphate dehydrogenase deficient individuals have less NADPH available for the reduction of oxidized glutathione via glutathione reductase. Thus their basal ratio of oxidized to reduced glutathione is significantly higher than that of patients who express glucose-6-phosphate dehydrogenase, normally, making them unable to effectively respond to high levels of reactive oxygen species, which causes cell lysis. [28]

Monitoring glutathione reductase activity

The activity of glutathione reductase is used as indicator for oxidative stress. The activity can be monitored by the NADPH consumption, with absorbance at 340 nm, or the formed GSH can be visualized by Ellman's reagent. [29] Alternatively the activity can be measured using roGFP (redox-sensitive Green Fluorescent Protein). [30]

In plants

As it does in human cells, glutathione reductase helps to protect plant cells from reactive oxygen species. In plants, reduced glutathione participates in the glutathione-ascorbate cycle in which reduced glutathione reduces dehydroascorbate, a reactive byproduct of the reduction of hydrogen peroxide. In particular, glutathione reductase contributes to plants' response to abiotic stress. [31] The enzyme's activity has been shown to be modulated in response to metals, metalloids, salinity, drought, UV radiation and heat induced stress. [31]

History

Glutathione reductase was first purified in 1955 at Yale University by P. Janmeda. [32] Janmeda also identified NADPH as the primary electron donor for the enzyme. Later groups confirmed the presence of FAD and the thiol group, and an initial mechanism was suggested for the mechanism in 1965. [33] [34] The initial (low resolution) structure of glutathione reductase was solved in 1977. This was quickly followed by a 3Å structure by Shulze et al. in 1978. [35] Glutathione reductase has been studied exhaustively since these early experiments, and is subsequently one of the most well characterized enzymes to date.

Interactive pathway map

Interactive pathway can be found here: pathway map

Related Research Articles

<span class="mw-page-title-main">Glutathione</span> Ubiquitous antioxidant compound in living organisms

Glutathione 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, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine.

<span class="mw-page-title-main">Glutathione peroxidase</span> Enzyme family protecting the organism from oxidative damages

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 hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water.

<span class="mw-page-title-main">Protein disulfide-isomerase</span> Class of enzymes

Protein disulfide isomerase, or PDI, is an enzyme in the endoplasmic reticulum (ER) in eukaryotes and the periplasm of bacteria that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold. This allows proteins to quickly find the correct arrangement of disulfide bonds in their fully folded state, and therefore the enzyme acts to catalyze protein folding.

Thioredoxin reductases are enzymes that reduce thioredoxin (Trx). Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. In bacteria TrxR also catalyzes the reduction of glutaredoxin like proteins known as NrdH. Both classes are flavoproteins which function as homodimers. Each monomer contains a FAD prosthetic group, a NADPH binding domain, and an active site containing a redox-active disulfide bond.

<span class="mw-page-title-main">Trypanothione</span> Chemical compound

Trypanothione is an unusual form of glutathione containing two molecules of glutathione joined by a spermidine (polyamine) linker. It is found in parasitic protozoa such as leishmania and trypanosomes. These protozoal parasites are the cause of leishmaniasis, sleeping sickness and Chagas' disease. Trypanothione was discovered by Alan Fairlamb. Its structure was proven by chemical synthesis. It is present mainly in the Kinetoplastida but can be found in other parasitic protozoa such as Entamoeba histolytica. Since this thiol is absent from humans and is essential for the survival of the parasites, the enzymes that make and use this molecule are targets for the development of new drugs to treat these diseases.

<span class="mw-page-title-main">Thioredoxin</span>

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-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the developing embryo. Although not entirely understood, thioredoxin is linked to medicine through their response to reactive oxygen species (ROS). In plants, thioredoxins regulate a spectrum of critical functions, ranging from photosynthesis to growth, flowering and the development and germination of seeds. Thioredoxins play a role in cell-to-cell communication.

Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds. The study of drug metabolism is called pharmacokinetics.

<span class="mw-page-title-main">Flavin adenine dinucleotide</span> Redox-active coenzyme

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which may be in the form of FAD or flavin mononucleotide (FMN). Many flavoproteins are known: components of the succinate dehydrogenase complex, α-ketoglutarate dehydrogenase, and a component of the pyruvate dehydrogenase complex.

Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.

<span class="mw-page-title-main">Glutathione disulfide</span> Chemical compound

Glutathione disulfide (GSSG) is a disulfide derived from two glutathione molecules.

The polyol pathway is a two-step process that converts glucose to fructose. In this pathway glucose is reduced to sorbitol, which is subsequently oxidized to fructose. It is also called the sorbitol-aldose reductase pathway.

<span class="mw-page-title-main">Glutathione synthetase</span> Enzyme

Glutathione synthetase (GSS) is the second enzyme in the glutathione (GSH) biosynthesis pathway. It catalyses the condensation of gamma-glutamylcysteine and glycine, to form glutathione. Glutathione synthetase is also a potent antioxidant. It is found in many species including bacteria, yeast, mammals, and plants.

<span class="mw-page-title-main">Peroxiredoxin</span> Family of antioxidant enzymes

Peroxiredoxins 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 PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, and PRDX6. The physiological importance of peroxiredoxins is indicated by their relative abundance. Their function is the reduction of peroxides, specifically hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite.

<span class="mw-page-title-main">NADH peroxidase</span>

In enzymology, a NADH peroxidase (EC 1.11.1.1) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">NADPH—hemoprotein reductase</span> Enzyme

In enzymology, a NADPH—hemoprotein reductase is an enzyme that catalyzes the chemical reaction

Glutamate–cysteine ligase (GCL) EC 6.3.2.2), previously known as γ-glutamylcysteine synthetase (GCS), is the first enzyme of the cellular glutathione (GSH) biosynthetic pathway that catalyzes the chemical reaction:

The ascorbate-glutathione cycle, sometimes Foyer-Halliwell-Asada pathway, is a metabolic pathway that detoxifies hydrogen peroxide (H2O2), a reactive oxygen species that is produced as a waste product in metabolism. The cycle involves the antioxidant metabolites: ascorbate, glutathione and NADPH and the enzymes linking these metabolites.

<span class="mw-page-title-main">Bacterial glutathione transferase</span>

Bacterial glutathione transferases are part of a superfamily of enzymes that play a crucial role in cellular detoxification. The primary role of GSTs is to catalyze the conjugation of glutathione (GSH) with the electrophilic centers of a wide variety of molecules. The most commonly known substrates of GSTs are xenobiotic synthetic chemicals. There are also classes of GSTs that utilize glutathione as a cofactor rather than a substrate. Often these GSTs are involved in reduction of reactive oxidative species toxic to the bacterium. Conjugation with glutathione receptors renders toxic substances more soluble, and therefore more readily exocytosed from the cell.

<i>S</i>-Nitrosoglutathione Chemical compound

S-Nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol (SNO) that plays a critical role in nitric oxide (NO) signaling and is a source of bioavailable NO. NO coexists in cells with SNOs that serve as endogenous NO carriers and donors. SNOs spontaneously release NO at different rates and can be powerful terminators of free radical chain propagation reactions, by reacting directly with ROO• radicals, yielding nitro derivatives as end products. NO is generated intracellularly by the nitric oxide synthase (NOS) family of enzymes: nNOS, eNOS and iNOS while the in vivo source of many of the SNOs is unknown. In oxygenated buffers, however, formation of SNOs is due to oxidation of NO to dinitrogen trioxide (N2O3). Some evidence suggests that both exogenous NO and endogenously derived NO from nitric oxide synthases can react with glutathione to form GSNO.

Oxidation response is stimulated by a disturbance in the balance between the production of reactive oxygen species and antioxidant responses, known as oxidative stress. Active species of oxygen naturally occur in aerobic cells and have both intracellular and extracellular sources. These species, if not controlled, damage all components of the cell, including proteins, lipids and DNA. Hence cells need to maintain a strong defense against the damage. The following table gives an idea of the antioxidant defense system in bacterial system.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000104687 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031584 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Deponte M (May 2013). "Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes". Biochim. Biophys. Acta. 1830 (5): 3217–66. doi: 10.1016/j.bbagen.2012.09.018 . PMID   23036594.
  6. ↑ Meister A (November 1988). "Glutathione metabolism and its selective modification". J. Biol. Chem. 263 (33): 17205–8. doi: 10.1016/S0021-9258(19)77815-6 . PMID   3053703.
  7. ↑ Mannervik B (August 1987). "The enzymes of glutathione metabolism: an overview". Biochem. Soc. Trans. 15 (4): 717–8. doi:10.1042/bst0150717. PMID   3315772.
  8. 1 2 Kanzok SM, Fechner A, Bauer H, Ulschmid JK, Müller HM, Botella-Munoz J, Schneuwly S, Schirmer R, Becker K (2001). "Substitution of the thioredoxin system for glutathione reductase in Drosophila melanogaster". Science. 291 (5504): 643–6. Bibcode:2001Sci...291..643K. doi:10.1126/science.291.5504.643. PMID   11158675.
  9. ↑ Krauth-Siegel RL, Comini MA (2008). "Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism". Biochim Biophys Acta. 1780 (11): 1236–48. doi:10.1016/j.bbagen.2008.03.006. PMID   18395526.
  10. ↑ Grisham, Reginald H. Garrett,... Charles M. (2005). Biochemistry (3rd ed.). Belmont, CA: Thomson Brooks/Cole. ISBN   0534490336.{{cite book}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Masella R, Di Benedetto R, Varì R, Filesi C, Giovannini C (October 2005). "Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes". J. Nutr. Biochem. 16 (10): 577–86. doi:10.1016/j.jnutbio.2005.05.013. PMID   16111877.
  12. ↑ Dym O, Eisenberg D (September 2001). "Sequence-structure analysis of FAD-containing proteins". Protein Sci. 10 (9): 1712–28. doi:10.1110/ps.12801. PMC   2253189 . PMID   11514662.
  13. ↑ Berkholz DS, Faber HR, Savvides SN, Karplus PA (October 2008). "Catalytic cycle of human glutathione reductase near 1 A resolution". J. Mol. Biol. 382 (2): 371–84. doi:10.1016/j.jmb.2008.06.083. PMC   2593804 . PMID   18638483.
  14. ↑ Rodríguez VM, Del Razo LM, Limón-Pacheco JH, Giordano M, Sánchez-Peña LC, Uribe-Querol E, Gutiérrez-Ospina G, Gonsebatt ME (March 2005). "Glutathione reductase inhibition and methylated arsenic distribution in Cd1 mice brain and liver". Toxicol. Sci. 84 (1): 157–66. doi: 10.1093/toxsci/kfi057 . PMID   15601678.
  15. ↑ Elliott AJ, Scheiber SA, Thomas C, Pardini RS (October 1992). "Inhibition of glutathione reductase by flavonoids. A structure-activity study". Biochem. Pharmacol. 44 (8): 1603–8. doi:10.1016/0006-2952(92)90478-2. PMID   1329770.
  16. ↑ Sarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, Karplus PA (May 2003). "Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development". J. Mol. Biol. 328 (4): 893–907. doi:10.1016/s0022-2836(03)00347-4. PMID   12729762.
  17. ↑ Buchholz K, Schirmer RH, Eubel JK, Akoachere MB, Dandekar T, Becker K, Gromer S (January 2008). "Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum". Antimicrob. Agents Chemother. 52 (1): 183–91. doi:10.1128/AAC.00773-07. PMC   2223905 . PMID   17967916.
  18. ↑ Müller T, Johann L, Jannack B, Brückner M, Lanfranchi DA, Bauer H, Sanchez C, Yardley V, Deregnaucourt C, Schrével J, Lanzer M, Schirmer RH, Davioud-Charvet E (August 2011). "Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites" (PDF). J. Am. Chem. Soc. 133 (30): 11557–71. doi:10.1021/ja201729z. PMID   21682307.
  19. ↑ Deponte M, Urig S, Arscott LD, Fritz-Wolf K, Réau R, Herold-Mende C, Koncarevic S, Meyer M, Davioud-Charvet E, Ballou DP, Williams CH, Becker K (May 2005). "Mechanistic studies on a novel, highly potent gold-phosphole inhibitor of human glutathione reductase". J. Biol. Chem. 280 (21): 20628–37. doi: 10.1074/jbc.M412519200 . PMID   15792952.
  20. ↑ Deponte M (May 2013). "Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes". Biochim. Biophys. Acta. 1830 (5): 3217–66. doi: 10.1016/j.bbagen.2012.09.018 . PMID   23036594.
  21. ↑ Champe PC, Harvey RA, Ferrier DR (2008). Biochemistry (fourth ed.). Lippincott Williams and Wilkins. ISBN   978-0-7817-6960-0.
  22. 1 2 Ramos PS, Oates JC, Kamen DL, Williams AH, Gaffney PM, Kelly JA, Kaufman KM, Kimberly RP, Niewold TB, Jacob CO, Tsao BP, Alarcón GS, Brown EE, Edberg JC, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, James JA, Guthridge JM, Merrill JT, Boackle SA, Freedman BI, Scofield RH, Stevens AM, Vyse TJ, Criswell LA, Moser KL, Alarcón-Riquelme ME, Langefeld CD, Harley JB, Gilkeson GS (June 2013). "Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry". J. Rheumatol. 40 (6): 842–9. doi:10.3899/jrheum.120989. PMC   3735344 . PMID   23637325.
  23. ↑ Gergely P, Grossman C, Niland B, Puskas F, Neupane H, Allam F, Banki K, Phillips PE, Perl A (January 2002). "Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus". Arthritis Rheum. 46 (1): 175–90. doi:10.1002/1529-0131(200201)46:1<175::AID-ART10015>3.0.CO;2-H. PMC   4020417 . PMID   11817589.
  24. 1 2 3 Yan J, Meng X, Wancket LM, Lintner K, Nelin LD, Chen B, Francis KP, Smith CV, Rogers LK, Liu Y (March 2012). "Glutathione reductase facilitates host defense by sustaining phagocytic oxidative burst and promoting the development of neutrophil extracellular traps". J. Immunol. 188 (5): 2316–27. doi:10.4049/jimmunol.1102683. PMC   3480216 . PMID   22279102.
  25. 1 2 Kamerbeek NM, Zwieten R, Boer M, Morren G, Vuil H, Bannink N, Lincke C, Dolman KM, Becker K, Schirmer RH, Gromer S, Roos D (2007). "Molecular basis of glutathione reductase deficiency in human blood cells". Blood. 109 (8): 3560–3566. doi: 10.1182/blood-2006-08-042531 . PMID   17185460.
  26. ↑ Roos D, Weening RS, Voetman AA, van Schaik ML, Bot AA, Meerhof LJ, Loos JA (May 1979). "Protection of phagocytic leukocytes by endogenous glutathione: studies in a family with glutathione reductase deficiency". Blood. 53 (5): 851–66. doi: 10.1182/blood.V53.5.851.851 . PMID   435643.
  27. ↑ Warsy AS, el-Hazmi MA (November 1999). "Glutathione reductase deficiency in Saudi Arabia". East. Mediterr. Health J. 5 (6): 1208–12. doi: 10.26719/1999.5.6.1208 . PMID   11924113.
  28. ↑ Cappellini MD, Fiorelli G (January 2008). "Glucose-6-phosphate dehydrogenase deficiency". Lancet. 371 (9606): 64–74. doi:10.1016/S0140-6736(08)60073-2. PMID   18177777. S2CID   29165746.
  29. ↑ Smith IK, Vierheller TL, Thorne CA (1988). "RAssay of glutathione reductase in crude tissue homogenates using 5,5'-dithiobis(2-nitrobenzoic acid)". Anal Biochem. 175 (2): 408–13. doi:10.1016/0003-2697(88)90564-7. PMID   3239770.
  30. ↑ Marty L, Siala W, Schwarzländer M, Fricker MD, Wirtz M, Sweetlove LJ, Meyer Y, Meyer AJ, Reichheld JP, Hell R (2009). "The NADPH-dependent thioredoxin system constitutes a functional backup for cytosolic glutathione reductase in Arabidopsis". Proc Natl Acad Sci U S A. 106 (22): 9109–14. Bibcode:2009PNAS..106.9109M. doi: 10.1073/pnas.0900206106 . PMC   2690020 . PMID   19451637.
  31. 1 2 Gill SS, Anjum NA, Hasanuzzaman M, Gill R, Trivedi DK, Ahmad I, Pereira E, Tuteja N (September 2013). "Glutathione and glutathione reductase: a boon in disguise for plant abiotic stress defense operations". Plant Physiol. Biochem. 70: 204–12. doi:10.1016/j.plaphy.2013.05.032. PMID   23792825.
  32. ↑ Racker E (December 1955). "Glutathione reductase from bakers' yeast and beef liver". J. Biol. Chem. 217 (2): 855–65. doi: 10.1016/S0021-9258(18)65950-2 . PMID   13271446.
  33. ↑ Massey V, Williams CH (November 1965). "On the reaction mechanism of yeast glutathione reductase". J. Biol. Chem. 240 (11): 4470–80. doi: 10.1016/S0021-9258(18)97085-7 . PMID   4378936.
  34. ↑ Mapson LW, Isherwood FA (January 1963). "Glutathione reductase from germinated peas". Biochem. J. 86: 173–91. doi:10.1042/bj0860173. PMC   1201730 . PMID   13932735.
  35. ↑ Schulz GE, Schirmer RH, Sachsenheimer W, Pai EF (May 1978). "The structure of the flavoenzyme glutathione reductase". Nature. 273 (5658): 120–4. Bibcode:1978Natur.273..120S. doi:10.1038/273120a0. PMID   25387. S2CID   4153363.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.