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Identification
Name Glutathione
Accession Number DB00143 (EXPT01650, NUTR00029)
Type small molecule
Groups approved, nutraceutical
Description

A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
5-L-Glutamyl-L-cysteinylglycine
gamma-L-Glutamyl-L-cysteinyl-glycine
Gluthathione
GSH
N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine
Salts Not Available
Brand names
Name Company
Copren
Isethion
Ledac
Neuthion
Tathion
Brand mixtures
Brand Name Ingredients
Amo Endosol Extra Calcium Chloride + Dextrose + Glutathione Disulfide + Magnesium Chloride + Potassium Chloride + Sodium Bicarbonate + Sodium Chloride + Sodium Phosphate Dibasic
BSS Plus Calcium Chloride + Dextrose + Glutathione Disulfide + Magnesium Chloride + Potassium Chloride + Sodium Bicarbonate + Sodium Chloride + Sodium Phosphate Dibasic
Categories
  • Dietary supplement
  • Micronutrient
CAS number 70-18-8
Weight Average: 307.323
Monoisotopic: 307.083805981
Chemical Formula C10H17N3O6S
InChI Key InChIKey=RWSXRVCMGQZWBV-WDSKDSINSA-N
InChI
InChI=1S/C10H17N3O6S/c11-5(10(18)19)1-2-7(14)13-6(4-20)9(17)12-3-8(15)16/h5-6,20H,1-4,11H2,(H,12,17)(H,13,14)(H,15,16)(H,18,19)/t5-,6-/m0/s1
Plain Text
IUPAC Name
(2S)-2-amino-4-{[(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl]carbamoyl}butanoic acid
SMILES
N[C@@H](CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Polypeptides
  • Carboxylic Acids and Derivatives
Substructures
  • Polypeptides
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Thiols
  • Carboxamides and Derivatives
  • Amino Acids
Pharmacology
Indication For nutritional supplementation, also for treating dietary shortage or imbalance
Pharmacodynamics Not Available
Mechanism of action Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. GSH is known as a cofactor in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is capable of participating in non-enzymatic conjugation with some chemicals, as it is hypothesized to do to a significant extent with n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450 reactive metabolite formed by toxic overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein sulfhydryl groups which would otherwise be toxically adducted. The preferred medical treatment to an overdose of this nature, whose efficacy has been consistently supported in literature, is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and allow a usable GSH pool.
Absorption Research suggests that glutathione is not orally bioactive, and that very little of oral glutathione tablets or capsules is actually absorbed by the body.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity ORL-MUS LD50 5000 mg/kg, IPR-MUS LD50 4020 mg/kg, SCU-MUS LD50 5000 mg/kg, IVN-RBT LD50 > 2000 mg/kg, IMS-MUS LD50 4000 mg/kg
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Glutathione crystals 21.32 USD g
Glutathione-l reduced powder 10.71 USD g
L-glutathione powder 3.0 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 195 °C PhysProp
logP -6.4 Not Available
Predicted Properties
Property Value Source
water solubility 8.79e-01 g/l ALOGPS
logP -2.7 ALOGPS
logP -4.9 ChemAxon
logS -2.5 ALOGPS
pKa (strongest acidic) 1.94 ChemAxon
pKa (strongest basic) 9.22 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 6 ChemAxon
polar surface area 158.82 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 69.11 ChemAxon
polarizability 29.11 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Struzynska L, Chalimoniuk M, Sulkowski G: The role of astroglia in Pb-exposed adult rat brain with respect to glutamate toxicity. Toxicology. 2005 Sep 1;212(2-3):185-94. Pubmed
  2. Witschi A, Reddy S, Stofer B, Lauterburg BH: The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992;43(6):667-9. Pubmed
  3. Yim CY, Hibbs JB Jr, McGregor JR, Galinsky RE, Samlowski WE: Use of N-acetyl cysteine to increase intracellular glutathione during the induction of antitumor responses by IL-2. J Immunol. 1994 Jun 15;152(12):5796-805. Pubmed
  4. Drevet JR: The antioxidant glutathione peroxidase family and spermatozoa: a complex story. Mol Cell Endocrinol. 2006 May 16;250(1-2):70-9. Epub 2006 Jan 19. Pubmed
  5. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND: Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92. Pubmed
External Links
Resource Link
KEGG Drug D00014 Link_out
KEGG Compound C00051 Link_out
PubChem Compound 124886 Link_out
PubChem Substance 46504598 Link_out
ChemSpider 111188 Link_out
ChEBI 16856 Link_out
ChEMBL 16856 Link_out
PharmGKB PA449780 Link_out
HET GSH Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/glu_0126.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Glutathione Link_out
ATC Codes
  • V03AB32
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (71.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Microsomal glutathione S-transferase 3

Pharmacological action: unknown

Also functions as a glutathione peroxidase

Organism class: human
UniProt ID: O14880 Link_out
Gene: MGST3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ago H, Kanaoka Y, Irikura D, Lam BK, Shimamura T, Austen KF, Miyano M: Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis. Nature. 2007 Aug 2;448(7153):609-12. Epub 2007 Jul 15. Pubmed

2. Glutathione-requiring prostaglandin D synthase

Pharmacological action: unknown

Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation

Organism class: human
UniProt ID: O60760 Link_out
Gene: HPGDS
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Aritake K, Kado Y, Inoue T, Miyano M, Urade Y: Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase. J Biol Chem. 2006 Jun 2;281(22):15277-86. Epub 2006 Mar 17. Pubmed
  4. Inoue T, Okano Y, Kado Y, Aritake K, Irikura D, Uodome N, Okazaki N, Kinugasa S, Shishitani H, Matsumura H, Kai Y, Urade Y: First determination of the inhibitor complex structure of human hematopoietic prostaglandin D synthase. J Biochem (Tokyo). 2004 Mar;135(3):279-83. Pubmed
  5. Urade Y, Kitahama K, Ohishi H, Kaneko T, Mizuno N, Hayaishi O: Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9070-4. Pubmed
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

3. Thioredoxin domain-containing protein 12

Pharmacological action: unknown

Possesses significant protein thiol-disulfide oxidase activity

Organism class: human
UniProt ID: O95881 Link_out
Gene: TXNDC12 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

4. Glutathione S-transferase A1

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P08263 Link_out
Gene: GSTA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kim I, Keam B, Lee KH, Kim JH, Oh SY, Ra EK, Yoon SS, Park SS, Kim CS, Park S, Hong YC, Kim BK: Glutathione S-transferase A1 polymorphisms and acute graft-vs.-host disease in HLA-matched sibling allogeneic hematopoietic stem cell transplantation. Clin Transplant. 2007 Mar-Apr;21(2):207-13. Pubmed
  2. Soderdahl T, Kuppers-Munther B, Heins N, Edsbagge J, Bjorquist P, Cotgreave I, Jernstrom B: Glutathione transferases in hepatocyte-like cells derived from human embryonic stem cells. Toxicol In Vitro. 2007 Aug;21(5):929-37. Epub 2007 Feb 2. Pubmed
  3. Jonsson LS, Broberg K, Bergendorf U, Axmon A, Littorin M, Jonsson BA: Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries. Int Arch Occup Environ Health. 2007 Jul;80(7):589-98. Epub 2007 Feb 28. Pubmed
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

5. Glutathione S-transferase A2

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P09210 Link_out
Gene: GSTA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sharma P, Ahmad Shah Z, Kumar A, Islam F, Mishra KP: Role of combined administration of Tiron and glutathione against aluminum-induced oxidative stress in rat brain. J Trace Elem Med Biol. 2007;21(1):63-70. Epub 2007 Feb 6. Pubmed
  2. Skamarauskas J, Carter W, Fowler M, Madjd A, Lister T, Mavroudis G, Ray DE: The selective neurotoxicity produced by 3-chloropropanediol in the rat is not a result of energy deprivation. Toxicology. 2007 Apr 11;232(3):268-76. Epub 2007 Jan 21. Pubmed
  3. Ozkilic AC, Cengiz M, Ozaydin A, Cobanoglu A, Kanigur G: The role of N-acetylcysteine treatment on anti-oxidative status in patients with type II diabetes mellitus. J Basic Clin Physiol Pharmacol. 2006;17(4):245-54. Pubmed
  4. Guruvayoorappan C, Afira AH, Kuttan G: Antioxidant potential of Biophytum sensitivum extract in vitro and in vivo. J Basic Clin Physiol Pharmacol. 2006;17(4):255-67. Pubmed
  5. Gupta S, Sarotra P, Aggarwal R, Dutta N, Agnihotri N: Role of oxidative stress in celecoxib-induced renal damage in wistar rats. Dig Dis Sci. 2007 Nov;52(11):3092-8. Epub 2007 Mar 31. Pubmed

6. Microsomal glutathione S-transferase 1

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Has a wide substrate specificity

Organism class: human
UniProt ID: P10620 Link_out
Gene: MGST1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Siritantikorn A, Johansson K, Ahlen K, Rinaldi R, Suthiphongchai T, Wilairat P, Morgenstern R: Protection of cells from oxidative stress by microsomal glutathione transferase 1. Biochem Biophys Res Commun. 2007 Apr 6;355(2):592-6. Epub 2007 Feb 12. Pubmed
  2. Busenlehner LS, Alander J, Jegerscohld C, Holm PJ, Bhakat P, Hebert H, Morgenstern R, Armstrong RN: Location of substrate binding sites within the integral membrane protein microsomal glutathione transferase-1. Biochemistry. 2007 Mar 13;46(10):2812-22. Epub 2007 Feb 13. Pubmed

7. S-formylglutathione hydrolase

Pharmacological action: unknown

Serine hydrolase involved in the detoxification of formaldehyde

Organism class: human
UniProt ID: P10768 Link_out
Gene: ESD Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Yurimoto H, Lee B, Yano T, Sakai Y, Kato N: Physiological role of S-formylglutathione hydrolase in C(1) metabolism of the methylotrophic yeast Candida boidinii. Microbiology. 2003 Aug;149(Pt 8):1971-9. Pubmed
  4. Neben I, Sahm H, Kula MR: Studies on an enzyme, S-formylglutathione hydrolase, of the dissimilatory pathway of methanol in Candida boidinii. Biochim Biophys Acta. 1980 Jul 10;614(1):81-91. Pubmed
  5. Sabatier L, Hoffschir F, al Achkar WA, Turleau C, de Grouchy J, Dutrillaux B: The decrease of catalase or esterase D activity in patients with microdeletions of 11p or 13q does not increase their radiosensitivity. Ann Genet. 1989;32(3):144-8. Pubmed

8. Gamma-glutamyltranspeptidase 1

Pharmacological action: unknown

Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracelular GSH level. It is part of the cell antioxidant defense mechanism. Catalyzes the transfer of the glutamyl moiety of glutathione to amino acids and dipeptide acceptors. Alternatively, glutathione can be hydrolyzed to give Cys-Gly and gamma glutamate. Isoform 3 seems to be inactive

Organism class: human
UniProt ID: P19440 Link_out
Gene: GGT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ohkama-Ohtsu N, Zhao P, Xiang C, Oliver DJ: Glutathione conjugates in the vacuole are degraded by gamma-glutamyl transpeptidase GGT3 in Arabidopsis. Plant J. 2007 Mar;49(5):878-88. Pubmed
  2. Martin MN, Saladores PH, Lambert E, Hudson AO, Leustek T: Localization of members of the gamma-glutamyl transpeptidase family identifies sites of glutathione and glutathione S-conjugate hydrolysis. Plant Physiol. 2007 Aug;144(4):1715-32. Epub 2007 Jun 1. Pubmed
  3. Anilakumar KR, Nagaraj NS, Santhanam K: Reduction of hexachlorocyclohexane-induced oxidative stress and cytotoxicity in rat liver by Emblica officinalis gaertn. Indian J Exp Biol. 2007 May;45(5):450-4. Pubmed
  4. Adamis PD, Panek AD, Eleutherio EC: Vacuolar compartmentation of the cadmium-glutathione complex protects Saccharomyces cerevisiae from mutagenesis. Toxicol Lett. 2007 Aug 30;173(1):1-7. Epub 2007 Jun 14. Pubmed
  5. Zhu Y, Carvey PM, Ling Z: Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide. Neurochem Int. 2007 Mar;50(4):671-80. Epub 2007 Jan 13. Pubmed

9. Glutathione S-transferase Mu 2

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P28161 Link_out
Gene: GSTM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kurtovic S, Jansson R, Mannervik B: Colorimetric endpoint assay for enzyme-catalyzed iodide ion release for high-throughput screening in microtiter plates. Arch Biochem Biophys. 2007 Aug 15;464(2):284-7. Epub 2007 Apr 24. Pubmed
  2. Vararattanavech A, Ketterman AJ: A functionally conserved basic residue in glutathione transferases interacts with the glycine moiety of glutathione and is pivotal for enzyme catalysis. Biochem J. 2007 Sep 1;406(2):247-56. Pubmed
  3. Gallagher EP, Huisden CM, Gardner JL: Transfection of HepG2 cells with hGSTA4 provides protection against 4-hydroxynonenal-mediated oxidative injury. Toxicol In Vitro. 2007 Apr 27;. Pubmed
  4. Yalcinkaya S, Unlucerci Y, Uysal M: Methionine-supplemented diet augments hepatotoxicity and prooxidant status in chronically ethanol-treated rats. Exp Toxicol Pathol. 2007 Aug;58(6):455-9. Epub 2007 May 11. Pubmed
  5. Roh JY, Jung IH, Lee JY, Choi J: Toxic effects of di(2-ethylhexyl)phthalate on mortality, growth, reproduction and stress-related gene expression in the soil nematode Caenorhabditis elegans. Toxicology. 2007 Jul 31;237(1-3):126-33. Epub 2007 May 18. Pubmed

10. Glutaredoxin-1

Pharmacological action: unknown

Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins

Organism class: human
UniProt ID: P35754 Link_out
Gene: GLRX Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Diwakar L, Kenchappa RS, Annepu J, Ravindranath V: Downregulation of glutaredoxin but not glutathione loss leads to mitochondrial dysfunction in female mice CNS: implications in excitotoxicity. Neurochem Int. 2007 Jul;51(1):37-46. Epub 2007 Apr 5. Pubmed
  2. Rouhier N, Unno H, Bandyopadhyay S, Masip L, Kim SK, Hirasawa M, Gualberto JM, Lattard V, Kusunoki M, Knaff DB, Georgiou G, Hase T, Johnson MK, Jacquot JP: Functional, structural, and spectroscopic characterization of a glutathione-ligated [2Fe-2S] cluster in poplar glutaredoxin C1. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7379-84. Epub 2007 Apr 25. Pubmed
  3. Hakansson KO, Winther JR: Structure of glutaredoxin Grx1p C30S mutant from yeast. Acta Crystallogr D Biol Crystallogr. 2007 Mar;63(Pt 3):288-94. Epub 2007 Feb 21. Pubmed
  4. Lu J, Chew EH, Holmgren A: Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12288-93. Epub 2007 Jul 18. Pubmed
  5. Wang J, Pan S, Berk BC: Glutaredoxin mediates Akt and eNOS activation by flow in a glutathione reductase-dependent manner. Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1283-8. Epub 2007 Apr 12. Pubmed

11. Phospholipid hydroperoxide glutathione peroxidase, mitochondrial

Pharmacological action: unknown
Actions: cofactor

Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage

Organism class: human
UniProt ID: P36969 Link_out
Gene: GPX4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Moreno SG, Laux G, Brielmeier M, Bornkamm GW, Conrad M: Testis-specific expression of the nuclear form of phospholipid hydroperoxide glutathione peroxidase (PHGPx). Biol Chem. 2003 Apr;384(4):635-43. Pubmed
  4. Baek IJ, Seo DS, Yon JM, Lee SR, Jin Y, Nahm SS, Jeong JH, Choo YK, Kang JK, Lee BJ, Yun YW, Nam SY: Tissue expression and cellular localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in male mice. J Mol Histol. 2007 Jun;38(3):237-44. Epub 2007 May 15. Pubmed
  5. Nam SY, Baek IJ, Lee BJ, In CH, Jung EY, Yon JM, Ahn B, Kang JK, Yu WJ, Yun YW: Effects of 17beta-estradiol and tamoxifen on the selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA expression in male reproductive organs of rats. J Reprod Dev. 2003 Oct;49(5):389-96. Pubmed

12. Glutathione S-transferase Mu 5

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P46439 Link_out
Gene: GSTM5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Schnakenberg E, Breuer R, Werdin R, Dreikorn K, Schloot W: Susceptibility genes: GSTM1 and GSTM3 as genetic risk factors in bladder cancer. Cytogenet Cell Genet. 2000;91(1-4):234-8. Pubmed
  4. Rao AV, Shaha C: Multiple glutathione S-transferase isoforms are present on male germ cell plasma membrane. FEBS Lett. 2001 Oct 26;507(2):174-80. Pubmed

13. Glutathione peroxidase 6

Pharmacological action: unknown
Actions: cofactor

2 glutathione + H(2)O(2) = glutathione disulfide + 2 H(2)O

Organism class: human
UniProt ID: P59796 Link_out
Gene: GPX6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Brigelius-Flohe R: Glutathione peroxidases and redox-regulated transcription factors. Biol Chem. 2006 Oct-Nov;387(10-11):1329-35. Pubmed
  4. Myllyla V, Kihlstrom M, Takala TE, Tolonen U, Salminen A, Vihko V: Activities of some antioxidative and hexose monophosphate shunt enzymes of skeletal muscle in neuromuscular diseases. Acta Neurol Scand. 1986 Jul;74(1):17-24. Pubmed
  5. Giovannini C, Scazzocchio B, Matarrese P, Vari R, D’Archivio M, Di Benedetto R, Casciani S, Dessi MR, Straface E, Malorni W, Masella R: Apoptosis induced by oxidized lipids is associated with up-regulation of p66Shc in intestinal Caco-2 cells: protective effects of phenolic compounds. J Nutr Biochem. 2007 Jun 22;. Pubmed

14. Hydroxyacylglutathione hydrolase

Pharmacological action: unknown

Thiolesterase that catalyzes the hydrolysis of S-D- lactoyl-glutathione to form glutathione and D-lactic acid

Organism class: human
UniProt ID: Q16775 Link_out
Gene: HAGH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Ridderstrom M, Jemth P, Cameron AD, Mannervik B: The active-site residue tyr-175 in human glyoxalase II contributes to binding of glutathione derivatives. Biochim Biophys Acta. 2000 Sep 29;1481(2):344-8. Pubmed
  4. Chyan MK, Elia AC, Principato GB, Giovannini E, Rosi G, Norton SJ: S-fluorenylmethoxycarbonyl glutathione and diesters: inhibition of mammalian glyoxalase II. Enzyme Protein. 1994-1995;48(3):164-73. Pubmed
  5. Al-Timari A, Douglas KT: Inhibition by glutathione derivatives of bovine liver glyoxalase II (hydroxyacylglutathione hydrolase) as a probe of the N- and S-sites for substrate binding. Biochim Biophys Acta. 1986 Mar 28;870(2):219-25. Pubmed

15. Hypothetical protein

Pharmacological action: unknown
Organism class: human
UniProt ID: Q6NSD4 Link_out
Gene: GPX1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chattopadhyay S, Sahoo DK, Subudhi U, Chainy GB: Differential expression profiles of antioxidant enzymes and glutathione redox status in hyperthyroid rats: a temporal analysis. Comp Biochem Physiol C Toxicol Pharmacol. 2007 Sep;146(3):383-91. Epub 2007 May 3. Pubmed
  2. Du X, Takagi H: N-Acetyltransferase Mpr1 confers ethanol tolerance on Saccharomyces cerevisiae by reducing reactive oxygen species. Appl Microbiol Biotechnol. 2007 Jul;75(6):1343-51. Epub 2007 Mar 27. Pubmed
  3. Sheridan PA, Zhong N, Carlson BA, Perella CM, Hatfield DL, Beck MA: Decreased selenoprotein expression alters the immune response during influenza virus infection in mice. J Nutr. 2007 Jun;137(6):1466-71. Pubmed
  4. Walshe J, Serewko-Auret MM, Teakle N, Cameron S, Minto K, Smith L, Burcham PC, Russell T, Strutton G, Griffin A, Chu FF, Esworthy S, Reeve V, Saunders NA: Inactivation of glutathione peroxidase activity contributes to UV-induced squamous cell carcinoma formation. Cancer Res. 2007 May 15;67(10):4751-8. Pubmed
  5. Sordillo LM, O’Boyle N, Gandy JC, Corl CM, Hamilton E: Shifts in thioredoxin reductase activity and oxidant status in mononuclear cells obtained from transition dairy cattle. J Dairy Sci. 2007 Mar;90(3):1186-92. Pubmed

16. Glutathione peroxidase 4

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: Q6PI42 Link_out
Gene: GPX4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Baek IJ, Seo DS, Yon JM, Lee SR, Jin Y, Nahm SS, Jeong JH, Choo YK, Kang JK, Lee BJ, Yun YW, Nam SY: Tissue expression and cellular localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in male mice. J Mol Histol. 2007 Jun;38(3):237-44. Epub 2007 May 15. Pubmed
  2. Cejas P, Garcia-Cabezas MA, Casado E, Belda-Iniesta C, De Castro J, Fresno JA, Sereno M, Barriuso J, Espinosa E, Zamora P, Feliu J, Redondo A, Hardisson DA, Renart J, Gonzalez-Baron M: Phospholipid hydroperoxide glutathione peroxidase (PHGPx) expression is downregulated in poorly differentiated breast invasive ductal carcinoma. Free Radic Res. 2007 Jun;41(6):681-7. Pubmed
  3. Wang Z, Wang F, Duan R, Liu JY: Purification and physicochemical characterization of a recombinant phospholipid hydroperoxide glutathione peroxidase from Oryza sativa. J Biochem Mol Biol. 2007 May 31;40(3):412-8. Pubmed
  4. Bertelsmann H, Sieme H, Behne D, Kyriakopoulos A: Is the distribution of selenium and zinc in the sublocations of spermatozoa regulated? Ann N Y Acad Sci. 2007 Jan;1095:204-8. Pubmed
  5. Ding WQ, Lind SE: Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting cancer cells from docosahexaenoic acid-induced cytotoxicity. Mol Cancer Ther. 2007 Apr;6(4):1467-74. Pubmed

17. CDNA FLJ23636 fis, clone CAS07176

Pharmacological action: unknown
Organism class: human
UniProt ID: Q8TED1 Link_out
Gene: GPX8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

18. Glutathione peroxidase 7

Pharmacological action: unknown
Actions: cofactor

2 glutathione + H(2)O(2) = glutathione disulfide + 2 H(2)O

Organism class: human
UniProt ID: Q96SL4 Link_out
Gene: GPX7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Giovannini C, Scazzocchio B, Matarrese P, Vari R, D’Archivio M, Di Benedetto R, Casciani S, Dessi MR, Straface E, Malorni W, Masella R: Apoptosis induced by oxidized lipids is associated with up-regulation of p66Shc in intestinal Caco-2 cells: protective effects of phenolic compounds. J Nutr Biochem. 2007 Jun 22;. Pubmed

19. Microsomal glutathione S-transferase 2

Pharmacological action: unknown

Can catalyze the production of LTC4 from LTA4 and reduced glutathione. Can catalyze the conjugation of 1-chloro-2,4- dinitrobenzene with reduced glutathione

Organism class: human
UniProt ID: Q99735 Link_out
Gene: MGST2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ago H, Kanaoka Y, Irikura D, Lam BK, Shimamura T, Austen KF, Miyano M: Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis. Nature. 2007 Aug 2;448(7153):609-12. Epub 2007 Jul 15. Pubmed

20. Glutathione transferase omega-2

Pharmacological action: unknown

RX + glutathione = HX + R-S-glutathione

Organism class: human
UniProt ID: Q9H4Y5 Link_out
Gene: GSTO2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Whitbread AK, Masoumi A, Tetlow N, Schmuck E, Coggan M, Board PG: Characterization of the omega class of glutathione transferases. Methods Enzymol. 2005;401:78-99. Pubmed
  4. Board PG, Anders MW: Glutathione transferase omega 1 catalyzes the reduction of S-(phenacyl)glutathiones to acetophenones. Chem Res Toxicol. 2007 Jan;20(1):149-54. Pubmed
  5. Whitbread AK, Tetlow N, Eyre HJ, Sutherland GR, Board PG: Characterization of the human Omega class glutathione transferase genes and associated polymorphisms. Pharmacogenetics. 2003 Mar;13(3):131-44. Pubmed

21. Glutaredoxin-2, mitochondrial

Pharmacological action: unknown

Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release

Organism class: human
UniProt ID: Q9NS18 Link_out
Gene: GLRX2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hashemy SI, Johansson C, Berndt C, Lillig CH, Holmgren A: Oxidation and S-nitrosylation of cysteines in human cytosolic and mitochondrial glutaredoxins: effects on structure and activity. J Biol Chem. 2007 May 11;282(19):14428-36. Epub 2007 Mar 13. Pubmed
  2. Sagemark J, Elgan TH, Burglin TR, Johansson C, Holmgren A, Berndt KD: Redox properties and evolution of human glutaredoxins. Proteins. 2007 Sep 1;68(4):879-92. Pubmed
  3. Sheng J, Ye J, Rosen BP: Crystallization and preliminary X-ray crystallographic analysis of Escherichia coliglutaredoxin 2 in complex with glutathione and of a cysteine-less variant without glutathione. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Apr 1;63(Pt 4):280-2. Epub 2007 Mar 12. Pubmed

22. Lactoylglutathione lyase

Pharmacological action: unknown

Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione

Organism class: human
UniProt ID: Q04760 Link_out
Gene: GLO1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Barati MT, Merchant ML, Kain AB, Jevans AW, McLeish KR, Klein JB: Proteomic Analysis Defines Altered Cellular Redox Pathways and Advanced Glycation End Product (AGE) Metabolism in Glomeruli of db/db Diabetic Mice. Am J Physiol Renal Physiol. 2007 Jul 3;. Pubmed
  2. Deponte M, Sturm N, Mittler S, Harner M, Mack H, Becker K: Allosteric Coupling of Two Different Functional Active Sites in Monomeric Plasmodium falciparum Glyoxalase I. J Biol Chem. 2007 Sep 28;282(39):28419-30. Epub 2007 Jul 30. Pubmed

23. Leukotriene C4 synthase

Pharmacological action: unknown

Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4

Organism class: human
UniProt ID: Q16873 Link_out
Gene: LTC4S Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggstrom JZ, Nordlund P: Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase. Nature. 2007 Aug 2;448(7153):613-6. Epub 2007 Jul 15. Pubmed
  2. Ago H, Kanaoka Y, Irikura D, Lam BK, Shimamura T, Austen KF, Miyano M: Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis. Nature. 2007 Aug 2;448(7153):609-12. Epub 2007 Jul 15. Pubmed

24. Glutathione reductase, mitochondrial

Pharmacological action: unknown

Maintains high levels of reduced glutathione in the cytosol

Organism class: human
UniProt ID: P00390 Link_out
Gene: GSR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Messarah M, Boulakoud MS, Boumendjel A, Abdennour C, El Feki A: The impact of thyroid activity variations on some oxidizing-stress parameters in rats. C R Biol. 2007 Feb;330(2):107-12. Epub 2006 Dec 12. Pubmed
  2. Brocardo PS, Assini F, Franco JL, Pandolfo P, Muller YM, Takahashi RN, Dafre AL, Rodrigues AL: Zinc attenuates malathion-induced depressant-like behavior and confers neuroprotection in the rat brain. Toxicol Sci. 2007 May;97(1):140-8. Epub 2007 Feb 27. Pubmed
  3. Guruvayoorappan C, Afira AH, Kuttan G: Antioxidant potential of Biophytum sensitivum extract in vitro and in vivo. J Basic Clin Physiol Pharmacol. 2006;17(4):255-67. Pubmed
  4. Markaryan AA, Dubinskaya VA, Dargaeva TD: Peroxide-eliminating oxidoreductases as biosensors of antioxidant components of medicinal plants. Bull Exp Biol Med. 2006 Jul;142(1):55-6. Pubmed
  5. Maity S, Roy S, Chaudhury S, Bhattacharya S: Antioxidant responses of the earthworm Lampito mauritii exposed to Pb and Zn contaminated soil. Environ Pollut. 2007 May 16;. Pubmed

25. Glutathione synthetase

Pharmacological action: unknown
Organism class: human
UniProt ID: P48637 Link_out
Gene: GSS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Herrera K, Cahoon RE, Kumaran S, Jez J: Reaction mechanism of glutathione synthetase from Arabidopsis thaliana: site-directed mutagenesis of active site residues. J Biol Chem. 2007 Jun 8;282(23):17157-65. Epub 2007 Apr 22. Pubmed
  2. Mohanpuria P, Rana NK, Yadav SK: Cadmium induced oxidative stress influence on glutathione metabolic genes of Camellia sinensis (L.) O. Kuntze. Environ Toxicol. 2007 Aug;22(4):368-74. Pubmed
  3. Forcella M, Berra E, Giacchini R, Parenti P: Antioxidant defenses preserve membrane transport activity in Chironomus riparius larvae exposed to anoxia. Arch Insect Biochem Physiol. 2007 Aug;65(4):181-94. Pubmed
  4. Janaky R, Dohovics R, Saransaari P, Oja SS: Modulation of [3H]dopamine release by glutathione in mouse striatal slices. Neurochem Res. 2007 Aug;32(8):1357-64. Epub 2007 Mar 31. Pubmed
  5. Bridges CC, Battle JR, Zalups RK: Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells. Toxicol Appl Pharmacol. 2007 Jun 1;221(2):251-60. Epub 2007 Mar 23. Pubmed

26. Glutathione S-transferase Mu 1

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P09488 Link_out
Gene: GSTM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Moore LE, Malats N, Rothman N, Real FX, Kogevinas M, Karami S, Garcia-Closas R, Silverman D, Chanock S, Welch R, Tardon A, Serra C, Carrato A, Dosemeci M, Garcia-Closas M: Polymorphisms in one-carbon metabolism and trans-sulfuration pathway genes and susceptibility to bladder cancer. Int J Cancer. 2007 Jun 1;120(11):2452-8. Pubmed
  2. Sakoda LC, Blackston CR, Xue K, Doherty JA, Ray RM, Lin MG, Stalsberg H, Gao DL, Feng Z, Thomas DB, Chen C: Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women. Breast Cancer Res Treat. 2007 Jul 12;. Pubmed
  3. Ouerhani S, Tebourski F, Slama MR, Marrakchi R, Rabeh M, Hassine LB, Ayed M, Elgaaied AB: The role of glutathione transferases M1 and T1 in individual susceptibility to bladder cancer in a Tunisian population. Ann Hum Biol. 2006 Sep-Dec;33(5-6):529-35. Pubmed
  4. Contreras-Vergara CA, Valenzuela-Soto E, Garcia-Orozco KD, Sotelo-Mundo RR, Yepiz-Plascencia G: A Mu-class glutathione S-transferase from gills of the marine shrimp Litopenaeus vannamei: purification and characterization. J Biochem Mol Toxicol. 2007;21(2):62-7. Pubmed
  5. Schwartzbaum JA, Ahlbom A, Lonn S, Warholm M, Rannug A, Auvinen A, Christensen HC, Henriksson R, Johansen C, Lindholm C, Malmer B, Salminen T, Schoemaker MJ, Swerdlow AJ, Feychting M: An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors. Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):559-65. Pubmed

27. Glutathione S-transferase kappa 1

Pharmacological action: unknown

Significant glutathione conjugating activity is found only with the model substrate, 1-chloro-2,4-dinitrobenzene (CDNB)

Organism class: human
UniProt ID: Q9Y2Q3 Link_out
Gene: GSTK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Robinson A, Huttley GA, Booth HS, Board PG: Modelling and bioinformatics studies of the human Kappa-class glutathione transferase predict a novel third glutathione transferase family with similarity to prokaryotic 2-hydroxychromene-2-carboxylate isomerases. Biochem J. 2004 May 1;379(Pt 3):541-52. Pubmed
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

28. Glutathione S-transferase A3

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)- pregnene-3,20-dione, precursors to testosterone and progesterone, respectively

Organism class: human
UniProt ID: Q16772 Link_out
Gene: GSTA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Board PG: Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4. Biochem J. 1998 Mar 1;330 ( Pt 2):827-31. Pubmed
  4. McHugh TE, Atkins WM, Racha JK, Kunze KL, Eaton DL: Binding of the aflatoxin-glutathione conjugate to mouse glutathione S-transferase A3-3 is saturated at only one ligand per dimer. J Biol Chem. 1996 Nov 1;271(44):27470-4. Pubmed
  5. McDonagh PD, Judah DJ, Hayes JD, Lian LY, Neal GE, Wolf CR, Roberts GC: Determinants of specificity for aflatoxin B1-8,9-epoxide in alpha-class glutathione S-transferases. Biochem J. 1999 Apr 1;339 ( Pt 1):95-101. Pubmed
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

29. Glutathione S-transferase Mu 3

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers

Organism class: human
UniProt ID: P21266 Link_out
Gene: GSTM3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Schwartzbaum JA, Ahlbom A, Lonn S, Warholm M, Rannug A, Auvinen A, Christensen HC, Henriksson R, Johansen C, Lindholm C, Malmer B, Salminen T, Schoemaker MJ, Swerdlow AJ, Feychting M: An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors. Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):559-65. Pubmed
  2. Moore LE, Brennan P, Karami S, Hung RJ, Hsu C, Boffetta P, Toro J, Zaridze D, Janout V, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Mukeria A, Holcatova I, Welch R, Chanock S, Rothman N, Chow WH: Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European Kidney Cancer Study. Carcinogenesis. 2007 Sep;28(9):1960-4. Epub 2007 Jul 7. Pubmed

30. Glutathione S-transferase A4

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4- hydroxynonenal (4-HNE)

Organism class: human
UniProt ID: O15217 Link_out
Gene: GSTA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gallagher EP, Huisden CM, Gardner JL: Transfection of HepG2 cells with hGSTA4 provides protection against 4-hydroxynonenal-mediated oxidative injury. Toxicol In Vitro. 2007 Apr 27;. Pubmed

31. Glutathione S-transferase Mu 4

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Active on 1- chloro-2,4-dinitrobenzene

Organism class: human
UniProt ID: Q03013 Link_out
Gene: GSTM4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Cantlay AM, Smith CA, Wallace WA, Yap PL, Lamb D, Harrison DJ: Heterogeneous expression and polymorphic genotype of glutathione S-transferases in human lung. Thorax. 1994 Oct;49(10):1010-4. Pubmed
  4. Beuckmann CT, Fujimori K, Urade Y, Hayaishi O: Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic prostaglandin E synthases in the human brain. Neurochem Res. 2000 May;25(5):733-8. Pubmed
  5. Efferth T, Volm M: Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. In Vivo. 2005 Jan-Feb;19(1):225-32. Pubmed
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

32. Glutathione S-transferase A5

Pharmacological action: unknown
Organism class: human
UniProt ID: Q7RTV2 Link_out
Gene: GSTA5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. McDonagh PD, Judah DJ, Hayes JD, Lian LY, Neal GE, Wolf CR, Roberts GC: Determinants of specificity for aflatoxin B1-8,9-epoxide in alpha-class glutathione S-transferases. Biochem J. 1999 Apr 1;339 ( Pt 1):95-101. Pubmed
  4. McLeod R, Ellis EM, Arthur JR, Neal GE, Judah DJ, Manson MM, Hayes JD: Protection conferred by selenium deficiency against aflatoxin B1 in the rat is associated with the hepatic expression of an aldo-keto reductase and a glutathione S-transferase subunit that metabolize the mycotoxin. Cancer Res. 1997 Oct 1;57(19):4257-66. Pubmed
  5. Kazi S, Ellis EM: Expression of rat liver glutathione-S-transferase GSTA5 in cell lines provides increased resistance to alkylating agents and toxic aldehydes. Chem Biol Interact. 2002 May 20;140(2):121-35. Pubmed

33. Glutathione S-transferase P

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P09211 Link_out
Gene: GSTP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ramachandran K, Navarro L, Gordian E, Das PM, Singal R: Methylation-mediated silencing of genes is not altered by selenium treatment of prostate cancer cells. Anticancer Res. 2007 Mar-Apr;27(2):921-5. Pubmed
  2. Kadokawa Y, Ohba K, Omagari K, Akazawa S, Hayashida K, Ohnita K, Takeshima F, Mizuta Y, Kohno S: Intracellular balance of oxidative stress and cytoprotective molecules in damaged interlobular bile ducts in autoimmune hepatitis and primary biliary cirrhosis: In situ detection of 8-hydroxydeoxyguanosine and glutathione-S-transferase-pi. Hepatol Res. 2007 Aug;37(8):620-7. Epub 2007 May 22. Pubmed

34. Glutathione transferase omega-1

Pharmacological action: unknown

Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities

Organism class: human
UniProt ID: P78417 Link_out
Gene: GSTO1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tulayakul P, Dong KS, Li JY, Manabe N, Kumagai S: The effect of feeding piglets with the diet containing green tea extracts or coumarin on in vitro metabolism of aflatoxin B1 by their tissues. Toxicon. 2007 Sep 1;50(3):339-48. Epub 2007 Apr 22. Pubmed
  2. Harju TH, Peltoniemi MJ, Rytila PH, Soini Y, Salmenkivi KM, Board PG, Ruddock LW, Kinnula VL: Glutathione S-transferase omega in the lung and sputum supernatants of COPD patients. Respir Res. 2007 Jul 6;8:48. Pubmed

35. Glutathione peroxidase 1

Pharmacological action: unknown
Actions: cofactor

Protects the hemoglobin in erythrocytes from oxidative breakdown

Organism class: human
UniProt ID: P07203 Link_out
Gene: GPX1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Destro-Bisol G, Spedini G: Anthropological survey on red cell glutathione peroxidase (GPX1) polymorphism in central western Africa: a tentative hypothesis on the interaction between GPX1*2 and Hb beta *S allelic products. Am J Phys Anthropol. 1989 Jun;79(2):217-24. Pubmed
  4. Liddell JR, Hoepken HH, Crack PJ, Robinson SR, Dringen R: Glutathione peroxidase 1 and glutathione are required to protect mouse astrocytes from iron-mediated hydrogen peroxide toxicity. J Neurosci Res. 2006 Aug 15;84(3):578-86. Pubmed
  5. Ursini F, Maiorino M: Native specific activity of glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does not differ between normo- and hypomotile human sperm samples. Int J Androl. 2005 Feb;28(1):61-2; author reply 63-4. Pubmed

36. Glutathione peroxidase 2

Pharmacological action: unknown
Actions: cofactor

Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides. Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors

Organism class: human
UniProt ID: P18283 Link_out
Gene: GPX2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Walshe J, Serewko-Auret MM, Teakle N, Cameron S, Minto K, Smith L, Burcham PC, Russell T, Strutton G, Griffin A, Chu FF, Esworthy S, Reeve V, Saunders NA: Inactivation of glutathione peroxidase activity contributes to UV-induced squamous cell carcinoma formation. Cancer Res. 2007 May 15;67(10):4751-8. Pubmed

37. Glutathione S-transferase theta-1

Pharmacological action: unknown

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2- epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4- nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide

Organism class: human
UniProt ID: P30711 Link_out
Gene: GSTT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ouerhani S, Tebourski F, Slama MR, Marrakchi R, Rabeh M, Hassine LB, Ayed M, Elgaaied AB: The role of glutathione transferases M1 and T1 in individual susceptibility to bladder cancer in a Tunisian population. Ann Hum Biol. 2006 Sep-Dec;33(5-6):529-35. Pubmed
  2. Schwartzbaum JA, Ahlbom A, Lonn S, Warholm M, Rannug A, Auvinen A, Christensen HC, Henriksson R, Johansen C, Lindholm C, Malmer B, Salminen T, Schoemaker MJ, Swerdlow AJ, Feychting M: An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors. Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):559-65. Pubmed
  3. Moore LE, Brennan P, Karami S, Hung RJ, Hsu C, Boffetta P, Toro J, Zaridze D, Janout V, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Mukeria A, Holcatova I, Welch R, Chanock S, Rothman N, Chow WH: Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European Kidney Cancer Study. Carcinogenesis. 2007 Sep;28(9):1960-4. Epub 2007 Jul 7. Pubmed
  4. Gawecki W, Kostrzewska-Poczekaj M, Gajecka M, Milecki P, Szyfter K, Szyfter W: The role of genetic factor in etiopathogenesis of squamous cell carcinoma of the head and neck in young adults. Eur Arch Otorhinolaryngol. 2007 Jul 26;. Pubmed
  5. Jonsson LS, Broberg K, Bergendorf U, Axmon A, Littorin M, Jonsson BA: Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries. Int Arch Occup Environ Health. 2007 Jul;80(7):589-98. Epub 2007 Feb 28. Pubmed

38. Maleylacetoacetate isomerase

Pharmacological action: unknown

Bifunctional enzyme showing minimal glutathione- conjugating activity with ethacrynic acid and 7-chloro-4- nitrobenz-2-oxa-1,3-diazole and maleylacetoacetate isomerase activity. Has also low glutathione peroxidase activity with T- butyl and cumene hydroperoxides. Is able to catalyze the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid

Organism class: human
UniProt ID: O43708 Link_out
Gene: GSTZ1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Fernandez-Canon JM, Baetscher MW, Finegold M, Burlingame T, Gibson KM, Grompe M: Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione-dependent nonenzymatic bypass in tyrosine catabolism. Mol Cell Biol. 2002 Jul;22(13):4943-51. Pubmed
  4. Hagedorn SR, Chapman PJ: Glutathione-independent maleylacetoacetate isomerase in gram-positive bacteria. J Bacteriol. 1985 Aug;163(2):803-5. Pubmed
  5. Lim CE, Matthaei KI, Blackburn AC, Davis RP, Dahlstrom JE, Koina ME, Anders MW, Board PG: Mice deficient in glutathione transferase zeta/maleylacetoacetate isomerase exhibit a range of pathological changes and elevated expression of alpha, mu, and pi class glutathione transferases. Am J Pathol. 2004 Aug;165(2):679-93. Pubmed

39. Epididymal secretory glutathione peroxidase

Pharmacological action: unknown
Actions: cofactor

Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathionine peroxidase-like protective system against peroxide damage in sperm membrane lipids

Organism class: human
UniProt ID: O75715 Link_out
Gene: GPX5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Koh CS, Didierjean C, Navrot N, Panjikar S, Mulliert G, Rouhier N, Jacquot JP, Aubry A, Shawkataly O, Corbier C: Crystal structures of a poplar thioredoxin peroxidase that exhibits the structure of glutathione peroxidases: insights into redox-driven conformational changes. J Mol Biol. 2007 Jul 13;370(3):512-29. Epub 2007 Apr 19. Pubmed

40. Glutathione peroxidase 3

Pharmacological action: unknown
Actions: cofactor

Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione

Organism class: human
UniProt ID: P22352 Link_out
Gene: GPX3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jacobson GA, Yee KC, Ng CH: Elevated plasma glutathione peroxidase concentration in acute severe asthma: comparison with plasma glutathione peroxidase activity, selenium and malondialdehyde. Scand J Clin Lab Invest. 2007;67(4):423-30. Pubmed
  2. Carmeli E, Bachar A, Barchad S: Biochemical assessments of total antioxidant status in active and nonactive female adults with intellectual disability. Res Sports Med. 2007 Apr-Jun;15(2):93-101. Pubmed
Enzymes

1. Glutathione S-transferase A2

Actions: substrate

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

UniProt ID: P09210 Link_out
Gene: GSTA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hayes JD, Flanagan JU, Jowsey IR: Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51-88. Pubmed
  2. Armstrong RN: Glutathione S-transferases: reaction mechanism, structure, and function. Chem Res Toxicol. 1991 Mar-Apr;4(2):131-40. Pubmed

2. Glutathione S-transferase A1

Actions: substrate

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

UniProt ID: P08263 Link_out
Gene: GSTA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hayes JD, Flanagan JU, Jowsey IR: Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51-88. Pubmed
  2. Armstrong RN: Glutathione S-transferases: reaction mechanism, structure, and function. Chem Res Toxicol. 1991 Mar-Apr;4(2):131-40. Pubmed
Transporters

1. Multidrug resistance-associated protein 1

Actions: substrate, inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J: Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta. 1997 May 22;1326(1):12-22. Pubmed
  2. Evers R, de Haas M, Sparidans R, Beijnen J, Wielinga PR, Lankelma J, Borst P: Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83. Pubmed
  3. Jedlitschky G, Leier I, Buchholz U, Barnouin K, Kurz G, Keppler D: Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res. 1996 Mar 1;56(5):988-94. Pubmed
  4. Minich T, Riemer J, Schulz JB, Wielinga P, Wijnholds J, Dringen R: The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes. J Neurochem. 2006 Apr;97(2):373-84. Epub 2006 Mar 15. Pubmed

2. Canalicular multispecific organic anion transporter 1

Actions: substrate, inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Paulusma CC, van Geer MA, Evers R, Heijn M, Ottenhoff R, Borst P, Oude Elferink RP: Canalicular multispecific organic anion transporter/multidrug resistance protein 2 mediates low-affinity transport of reduced glutathione. Biochem J. 1999 Mar 1;338 ( Pt 2):393-401. Pubmed
  2. Hagmann W, Nies AT, Konig J, Frey M, Zentgraf H, Keppler D: Purification of the human apical conjugate export pump MRP2 reconstitution and functional characterization as substrate-stimulated ATPase. Eur J Biochem. 1999 Oct 1;265(1):281-9. Pubmed
  3. Nishida T, Gatmaitan Z, Roy-Chowdhry J, Arias IM: Two distinct mechanisms for bilirubin glucuronide transport by rat bile canalicular membrane vesicles. Demonstration of defective ATP-dependent transport in rats (TR-) with inherited conjugated hyperbilirubinemia. J Clin Invest. 1992 Nov;90(5):2130-5. Pubmed
  4. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ: Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 2000 Feb;118(2):422-30. Pubmed
  5. Madon J, Hagenbuch B, Landmann L, Meier PJ, Stieger B: Transport function and hepatocellular localization of mrp6 in rat liver. Mol Pharmacol. 2000 Mar;57(3):634-41. Pubmed

3. Canalicular multispecific organic anion transporter 2

Actions: substrate

May act as an inducible transporter in the biliary and intestinal excretion of organic anions

UniProt ID: O15438 Link_out
Gene: ABCC3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P: Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem. 2001 Dec 7;276(49):46400-7. Pubmed

4. Multidrug resistance-associated protein 4

Actions: substrate

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lai L, Tan TM: Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem J. 2002 Feb 1;361(Pt 3):497-503. Pubmed

5. Multidrug resistance-associated protein 5

Actions: substrate

Acts as a multispecific organic anion pump which can transport nucleotide analogs

UniProt ID: O15440 Link_out
Gene: ABCC5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Minich T, Riemer J, Schulz JB, Wielinga P, Wijnholds J, Dringen R: The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes. J Neurochem. 2006 Apr;97(2):373-84. Epub 2006 Mar 15. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19