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Glutathione (T3D4352)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (42)XML
Targets (42)
Record Information
Version2.0
Creation Date2014-08-29 06:32:13 UTC
Update Date2014-12-24 20:26:47 UTC
Accession NumberT3D4352
Identification
Common NameGlutathione
ClassSmall Molecule
DescriptionGlutathione is a compound synthesized from cysteine, perhaps the most important member of the body's toxic waste disposal team. Like cysteine, glutathione contains the crucial thiol (-SH) group that makes it an effective antioxidant. There are virtually no living organisms on this planet-animal or plant whose cells don't contain some glutathione. Scientists have speculated that glutathione was essential to the very development of life on earth. Glutathione has many roles; in none does it act alone. It is a coenzyme in various enzymatic reactions. The most important of these are redox reactions, in which the thiol grouping on the cysteine portion of cell membranes protects against peroxidation; and conjugation reactions, in which glutathione (especially in the liver) binds with toxic chemicals in order to detoxify them. Glutathione is also important in red and white blood cell formation and throughout the immune system. glutathione's clinical uses include the prevention of oxygen toxicity in hyperbaric oxygen therapy, treatment of lead and other heavy metal poisoning, lowering of the toxicity of chemotherapy and radiation in cancer treatments, and reversal of cataracts. Glutathione 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 (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-Lactoyl-glutathione to glutathione and D-lactate. GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals, as in the case of n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by acetaminophen, that becomes toxic when GSH is depleted by an 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 thiol groups which would otherwise be covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and renew the usable GSH pool. 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.
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
5-L-Glutamyl-L-cysteinylglycine
Agifutol S
Bakezyme RX
Copren
Deltathione
gamma-Glutamylcysteinylglycine
gamma-L-Glutamyl-L-cysteinyl-glycine
gamma-L-Glutamyl-L-cysteinylglycine
Glutathion
Glutathione red
Glutathione reduced
Glutathione-SH
Glutatiol
Glutatione
Glutide
Glutinal
GSH
Isethion
L-g-Glutamyl-L-cysteinyl-glycine
L-gamma-Glutamyl-L-cysteinyl-glycine
L-gamma-Glutamyl-L-cysteinylglycine
L-Glutamyl-L-cysteinylglycine
L-Glutathione
L-Glutathione reduce
Ledac
N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine
Neuthion
Red. glutathione
Reduced glutathione
Tathion
Tathione
Triptide
Chemical FormulaC10H17N3O6S
Average Molecular Mass307.323 g/mol
Monoisotopic Mass307.084 g/mol
CAS Registry Number70-18-8
IUPAC Name(2S)-2-amino-4-{[(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl]carbamoyl}butanoic acid
Traditional Nameglutathione
SMILES[H][C@](N)(CCC(O)=N[C@@]([H])(CS)C(O)=NCC(O)=O)C(O)=O
InChI IdentifierInChI=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
InChI KeyInChIKey=RWSXRVCMGQZWBV-WDSKDSINSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as peptides. Peptides are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPeptides
Alternative Parents
Substituents
  • Alpha peptide
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid
  • Alpha-amino acid or derivatives
  • L-alpha-amino acid
  • Dicarboxylic acid or derivatives
  • Fatty acid
  • Amino acid or derivatives
  • Amino acid
  • Alkylthiol
  • Carboximidic acid
  • Carboximidic acid derivative
  • Carboxylic acid
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Hydrocarbon derivative
  • Primary aliphatic amine
  • Organic oxide
  • Organic oxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Amine
  • Organonitrogen compound
  • Organooxygen compound
  • Organosulfur compound
  • Organopnictogen compound
  • Primary amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
  • Membrane
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • All Tissues
Pathways
NameSMPDB LinkKEGG Link
Arachidonic Acid MetabolismSMP00075 map00590
Glutamate MetabolismSMP00072 map00250
Glutathione MetabolismSMP00015 map00480
Pyruvaldehyde DegradationSMP00459 Not Available
Gamma-Glutamyltransferase DeficiencySMP00183 Not Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point195°C
Boiling PointNot Available
Solubility292.5 mg/mL
LogP-6.4
Predicted Properties
PropertyValueSource
Water Solubility0.88 g/LALOGPS
logP-2.7ALOGPS
logP-4.9ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)1.94ChemAxon
pKa (Strongest Basic)9.22ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area158.82 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity69.11 m³·mol⁻¹ChemAxon
Polarizability29.11 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (x TMS)splash10-0a4i-0900000000-5841845f736f9a6676222014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (x TMS)splash10-0a4i-0900000000-bdecde153761cb67852e2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0900000000-5841845f736f9a6676222017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0900000000-bdecde153761cb67852e2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-1910000000-52bc43dd913b68d74f842017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-08fs-3960000000-63ce34def2ae94b955152017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0pb9-0921000000-88168b0a9f5fc5fead3f2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-7890000000-5853006f66d946dd3d2e2016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0596-9112300000-e82cf72540c283d8e3232017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-3795000000-d019cd7dcbad1f8a9e782012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-003r-9400000000-a83bf6292d41988256e32012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-305a92f8a9ffea58fa0e2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0009000000-e950bfc5867b391c69602012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0910000000-83f6c079d1112e74ecf42012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-003r-0910000000-5b243cf8bd357ab270b12012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0009000000-29ef335479f56b620d882012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0009001000-d1f5986166efa523d0242012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-056s-0495300000-dba7be381fd1ef7765272012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0920000000-de5b8a5a377324599b392012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-053r-0007920000-7500cef211e48c8ea2442012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0a4i-0119003000-4eb7ed4e2a4cf6a83c662012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0uki-0290000000-6893386899c6eed6a1a62012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-05g0-0190000000-cacc2de4ab18ed59798b2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0a4i-0009000000-6b4268add43ab66ef0152012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-08fr-0015009000-a01bdc13a34d6ce8416f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0uki-0290000000-ea94ec8247b4e025adbe2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0a4i-0039210000-e1f721157a9ea89959d62012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0a59-0039210000-35ce450ea95922abf0e12012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-0a4i-0009000000-9b01fba547d1fcde113a2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0006-0952000000-4a2a42699cf4aab2c5592012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-002f-2900000000-bd9ba27b48b1322b76182012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-004m-5900000000-cc7184d5bba50e6e49d02012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0a4i-9200000000-aecd0eb18a10c3ffb7ab2012-08-31View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0729-4492000000-78a928563adf9038ba592016-09-12View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 125 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
Toxicity Profile
Route of ExposureResearch suggests that glutathione is not orally bioactive, and that very little of oral glutathione tablets or capsules is actually absorbed by the body.
Mechanism of ToxicityGlutathione (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.
MetabolismNot Available
Toxicity ValuesORL-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
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor nutritional supplementation, also for treating dietary shortage or imbalance
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00143
HMDB IDHMDB00125
PubChem Compound ID124886
ChEMBL IDCHEMBL1543
ChemSpider ID111188
KEGG IDC00051
UniProt IDNot Available
OMIM ID
ChEBI ID16856
BioCyc IDOXIDIZED-GLUTATHIONE
CTD IDNot Available
Stitch IDNot Available
PDB IDGSH
ACToR IDNot Available
Wikipedia LinkGlutathione
References
Synthesis Reference

Akihiro Mizutani, “Complexes of polysaccharides or derivatives thereof with reduced glutathione and process for preparing said complexes.” U.S. Patent US4009264, issued February, 1971.

MSDSLink
General References
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  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. [8207209 ]
  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. [16427183 ]
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  8. Hung CR: Effect of lysozyme chloride on betel quid chewing aggravated gastric oxidative stress and hemorrhagic ulcer in diabetic rats. World J Gastroenterol. 2005 Oct 7;11(37):5853-8. [16270397 ]
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  11. Calabrese V, Scapagnini G, Ravagna A, Bella R, Butterfield DA, Calvani M, Pennisi G, Giuffrida Stella AM: Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: evidence for a protective role of acetylcarnitine. Neurochem Res. 2003 Sep;28(9):1321-8. [12938853 ]
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  14. Briz O, Romero MR, Martinez-Becerra P, Macias RI, Perez MJ, Jimenez F, San Martin FG, Marin JJ: OATP8/1B3-mediated cotransport of bile acids and glutathione: an export pathway for organic anions from hepatocytes? J Biol Chem. 2006 Oct 13;281(41):30326-35. Epub 2006 Jul 28. [16877380 ]
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  16. Nakayama Y, Kinoshita A, Tomita M: Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition. Theor Biol Med Model. 2005 May 9;2:18. [15882454 ]
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  18. Kawakami Y, Monobe M, Kuwabara K, Fujita T, Maeda M, Fujino O, Kojima S, Fukunaga Y: A comparative study of nitric oxide, glutathione, and glutathione peroxidase activities in cerebrospinal fluid from children with convulsive diseases/children with aseptic meningitis. Brain Dev. 2006 May;28(4):243-6. Epub 2006 Jan 10. [16376049 ]
  19. Kaynar H, Meral M, Turhan H, Keles M, Celik G, Akcay F: Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase activities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer. Cancer Lett. 2005 Sep 28;227(2):133-9. Epub 2005 Jan 8. [16112416 ]
  20. Tsai CC, Chen HS, Chen SL, Ho YP, Ho KY, Wu YM, Hung CC: Lipid peroxidation: a possible role in the induction and progression of chronic periodontitis. J Periodontal Res. 2005 Oct;40(5):378-84. [16105090 ]
  21. Wielandt AM, Vollrath V, Farias M, Chianale J: Bucillamine induces glutathione biosynthesis via activation of the transcription factor Nrf2. Biochem Pharmacol. 2006 Aug 14;72(4):455-62. Epub 2006 Jun 27. [16806086 ]
  22. Oztezcan S, Balkan J, Dogru-Abbasoglu S, Cevikbas U, Aykac-Toker G, Uysal M: Resistance of erythrocytes to lipid peroxidation in cirrhotic rats. Arch Med Res. 2005 Sep-Oct;36(5):459-63. [16099321 ]
  23. Schulpis KH, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S: The effect of L-cysteine and glutathione on inhibition of Na+, K+-ATPase activity by aspartame metabolites in human erythrocyte membrane. Eur J Clin Nutr. 2006 May;60(5):593-7. [16391576 ]
  24. Zamek-Gliszczynski MJ, Hoffmaster KA, Nezasa K, Tallman MN, Brouwer KL: Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites. Eur J Pharm Sci. 2006 Apr;27(5):447-86. Epub 2006 Feb 10. [16472997 ]
  25. Iwasaki Y, Hoshi M, Ito R, Saito K, Nakazawa H: Analysis of glutathione and glutathione disulfide in human saliva using hydrophilic interaction chromatography with mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jul 24;839(1-2):74-9. Epub 2006 Apr 18. [16621738 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Glutathione S-transferase A3
General Function:
Glutathione transferase activity
Specific Function:
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.
Gene Name:
GSTA3
Uniprot ID:
Q16772
Molecular Weight:
25301.355 Da
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. [17139284 ]
  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. [17016423 ]
  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. [9480897 ]
  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. [8910329 ]
  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. [10085232 ]
  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. [10592235 ]
Target Details
2. Glutathione S-transferase Mu 1
General Function:
Protein homodimerization activity
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name:
GSTM1
Uniprot ID:
P09488
Molecular Weight:
25711.555 Da
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. [17311259 ]
  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. 2008 May;109(1):143-55. Epub 2007 Jul 12. [17624589 ]
  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. [17381051 ]
  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. [17427177 ]
  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. [17372252 ]
  6. Wang CH, Wu HT, Cheng HM, Yen TJ, Lu IH, Chang HC, Jao SC, Shing TK, Li WS: Inhibition of glutathione S-transferase M1 by new gabosine analogues is essential for overcoming cisplatin resistance in lung cancer cells. J Med Chem. 2011 Dec 22;54(24):8574-81. doi: 10.1021/jm201131n. Epub 2011 Nov 23. [22085405 ]
Target Details
3. Glutathione S-transferase Mu 4
General Function:
Protein homodimerization activity
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Active on 1-chloro-2,4-dinitrobenzene.
Gene Name:
GSTM4
Uniprot ID:
Q03013
Molecular Weight:
25561.095 Da
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. [17139284 ]
  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. [17016423 ]
  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. [7974294 ]
  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. [10905636 ]
  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. [15796179 ]
  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. [10592235 ]
Target Details
4. Hematopoietic prostaglandin D synthase
General Function:
Protein homodimerization activity
Specific Function:
Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide.
Gene Name:
HPGDS
Uniprot ID:
O60760
Molecular Weight:
23343.65 Da
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. [17139284 ]
  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. [17016423 ]
  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. [16547010 ]
  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. 2004 Mar;135(3):279-83. [15113825 ]
  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. [8415655 ]
  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. [10592235 ]
Target Details
5. Gamma-glutamyltranspeptidase 1
General Function:
Glutathione hydrolase activity
Specific Function:
Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione releases free glutamate and the dipeptide, cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Isoform 3 seems to be inactive.
Gene Name:
GGT1
Uniprot ID:
P19440
Molecular Weight:
61409.67 Da
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. [17316176 ]
  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. [17545509 ]
  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. [17569287 ]
  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. [17644279 ]
  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. [17291629 ]
Target Details
6. Glutaredoxin-1
General Function:
Protein n-terminus binding
Specific Function:
Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.
Gene Name:
GLRX
Uniprot ID:
P35754
Molecular Weight:
11775.665 Da
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. [17512091 ]
  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. [17460036 ]
  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. [17327665 ]
  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. [17640917 ]
  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. [17431186 ]
Target Details
7. Glutathione S-transferase A2
General Function:
Glutathione transferase activity
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name:
GSTA2
Uniprot ID:
P09210
Molecular Weight:
25663.675 Da
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. [17317527 ]
  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. [17321661 ]
  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. [17338280 ]
  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. [17338281 ]
  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. [17401685 ]
Target Details
8. Glutathione S-transferase A5
General Function:
Glutathione transferase activity
Specific Function:
Not Available
Gene Name:
GSTA5
Uniprot ID:
Q7RTV2
Molecular Weight:
25721.725 Da
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. [17139284 ]
  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. [17016423 ]
  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. [10085232 ]
  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. [9331086 ]
  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. [12076520 ]
Target Details
9. Glutathione S-transferase Mu 2
General Function:
Receptor binding
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name:
GSTM2
Uniprot ID:
P28161
Molecular Weight:
25744.395 Da
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. [17490601 ]
  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. [17523921 ]
  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 Dec;21(8):1365-72. Epub 2007 Apr 27. [17553661 ]
  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. [17498936 ]
  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. [17604895 ]
Target Details
10. Glutathione S-transferase kappa 1
General Function:
Receptor binding
Specific Function:
Significant glutathione conjugating activity is found only with the model substrate, 1-chloro-2,4-dinitrobenzene (CDNB).
Gene Name:
GSTK1
Uniprot ID:
Q9Y2Q3
Molecular Weight:
25496.625 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.02 uMNot AvailableBindingDB 50422268
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. [17139284 ]
  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. [17016423 ]
  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. [14709161 ]
  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. [10592235 ]
  5. Klotz P, Slaoui-Hasnaoui A, Baneres JL, Duckert JF, Rossi JC, Kerbal A: Synthesis and glutathione S-transferase structure-affinity relationships of nonpeptide and peptidase-stable glutathione analogues. J Med Chem. 1998 Jun 18;41(13):2278-88. [9632361 ]
Target Details
11. Glutathione S-transferase omega-2
General Function:
Oxidoreductase activity
Specific Function:
Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA).
Gene Name:
GSTO2
Uniprot ID:
Q9H4Y5
Molecular Weight:
28253.52 Da
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. [17139284 ]
  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. [17016423 ]
  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. [16399380 ]
  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. [17226937 ]
  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. [12618591 ]
Target Details
12. Glutathione S-transferase theta-1
General Function:
Glutathione transferase activity
Specific Function:
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.
Gene Name:
GSTT1
Uniprot ID:
P30711
Molecular Weight:
27334.755 Da
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. [17381051 ]
  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. [17372252 ]
  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. [17617661 ]
  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 Dec;264(12):1459-65. Epub 2007 Jul 26. [17653748 ]
  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. [17333241 ]
Target Details
13. Glutathione peroxidase
General Function:
Glutathione peroxidase activity
Specific Function:
Not Available
Gene Name:
GPX1
Uniprot ID:
Q6NSD4
Molecular Weight:
16179.36 Da
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. [17561443 ]
  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. [17387467 ]
  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. [17513408 ]
  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. [17510403 ]
  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. [17297093 ]
Target Details
14. Glutathione peroxidase 1
General Function:
Sh3 domain binding
Specific Function:
Protects the hemoglobin in erythrocytes from oxidative breakdown.
Gene Name:
GPX1
Uniprot ID:
P07203
Molecular Weight:
22087.94 Da
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. [17139284 ]
  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. [17016423 ]
  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. [2742004 ]
  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. [16721761 ]
  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. [15679624 ]
Target Details
15. Glutathione peroxidase 6
General Function:
Glutathione peroxidase activity
Specific Function:
Not Available
Gene Name:
GPX6
Uniprot ID:
P59796
Molecular Weight:
24970.46 Da
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. [17139284 ]
  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. [17016423 ]
  3. Brigelius-Flohe R: Glutathione peroxidases and redox-regulated transcription factors. Biol Chem. 2006 Oct-Nov;387(10-11):1329-35. [17081103 ]
  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. [3532684 ]
  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. 2008 Feb;19(2):118-28. Epub 2007 Jun 27. [17588737 ]
Target Details
16. Glutathione reductase, mitochondrial
General Function:
Nadp binding
Specific Function:
Maintains high levels of reduced glutathione in the cytosol.
Gene Name:
GSR
Uniprot ID:
P00390
Molecular Weight:
56256.565 Da
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. [17303537 ]
  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. [17327255 ]
  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. [17338281 ]
  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. [17369902 ]
  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. 2008 Jan;151(1):1-7. Epub 2007 May 23. [17512104 ]
Target Details
17. Glutathione synthetase
General Function:
Protein homodimerization activity
Specific Function:
Not Available
Gene Name:
GSS
Uniprot ID:
P48637
Molecular Weight:
52384.325 Da
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. [17452339 ]
  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. [17607728 ]
  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. [17630655 ]
  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. [17401648 ]
  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. [17467761 ]
Target Details
18. Hydroxyacylglutathione hydrolase, mitochondrial
General Function:
Metal ion binding
Specific Function:
Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.
Gene Name:
HAGH
Uniprot ID:
Q16775
Molecular Weight:
33805.645 Da
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. [17139284 ]
  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. [17016423 ]
  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. [11018726 ]
  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. [8589803 ]
  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. [3955057 ]
Target Details
19. Maleylacetoacetate isomerase
General Function:
Protein homodimerization activity
Specific Function:
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.
Gene Name:
GSTZ1
Uniprot ID:
O43708
Molecular Weight:
24212.005 Da
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. [17139284 ]
  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. [17016423 ]
  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. [12052898 ]
  4. Hagedorn SR, Chapman PJ: Glutathione-independent maleylacetoacetate isomerase in gram-positive bacteria. J Bacteriol. 1985 Aug;163(2):803-5. [4019417 ]
  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. [15277241 ]
Target Details
20. Phospholipid hydroperoxide glutathione peroxidase, mitochondrial
General Function:
Phospholipid-hydroperoxide glutathione peroxidase activity
Specific Function:
Protects cells against membrane lipid peroxidation and cell death. Required for normal sperm development and male fertility. 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.
Gene Name:
GPX4
Uniprot ID:
P36969
Molecular Weight:
22174.52 Da
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. [17139284 ]
  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. [17016423 ]
  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. [12751792 ]
  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. [17503194 ]
  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. [14967915 ]
Target Details
21. S-formylglutathione hydrolase
General Function:
S-formylglutathione hydrolase activity
Specific Function:
Serine hydrolase involved in the detoxification of formaldehyde.
Gene Name:
ESD
Uniprot ID:
P10768
Molecular Weight:
31462.545 Da
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. [17139284 ]
  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. [17016423 ]
  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. [12904537 ]
  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. [7397203 ]
  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. [2554783 ]
Target Details
22. Glutathione S-transferase A1
General Function:
Glutathione transferase activity
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name:
GSTA1
Uniprot ID:
P08263
Molecular Weight:
25630.785 Da
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. [17425746 ]
  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. [17346923 ]
  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. [17333241 ]
  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. [10592235 ]
Target Details
23. Glutathione S-transferase Mu 5
General Function:
Glutathione transferase activity
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name:
GSTM5
Uniprot ID:
P46439
Molecular Weight:
25674.455 Da
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. [17139284 ]
  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. [17016423 ]
  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. [11173863 ]
  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. [11684093 ]
Target Details
24. Glutaredoxin-2, mitochondrial
General Function:
Protein disulfide oxidoreductase activity
Specific Function:
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.
Gene Name:
GLRX2
Uniprot ID:
Q9NS18
Molecular Weight:
18051.515 Da
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. [17355958 ]
  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. [17546662 ]
  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. [17401194 ]
Target Details
25. Thyrotropin receptor
General Function:
Thyroid-stimulating hormone receptor activity
Specific Function:
Receptor for thyrothropin. Plays a central role in controlling thyroid cell metabolism. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Also acts as a receptor for thyrostimulin (GPA2+GPB5).
Gene Name:
TSHR
Uniprot ID:
P16473
Molecular Weight:
86828.965 Da
References
  1. Polekhina G, Board PG, Blackburn AC, Parker MW: Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. Biochemistry. 2001 Feb 13;40(6):1567-76. [11327815 ]
  2. Ricci G, Turella P, De Maria F, Antonini G, Nardocci L, Board PG, Parker MW, Carbonelli MG, Federici G, Caccuri AM: Binding and kinetic mechanisms of the Zeta class glutathione transferase. J Biol Chem. 2004 Aug 6;279(32):33336-42. Epub 2004 Jun 1. [15173170 ]
  3. Board PG, Baker RT, Chelvanayagam G, Jermiin LS: Zeta, a novel class of glutathione transferases in a range of species from plants to humans. Biochem J. 1997 Dec 15;328 ( Pt 3):929-35. [9396740 ]
Target Details
26. Glutathione S-transferase Mu 3
General Function:
Protein homodimerization activity
Specific Function:
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.
Gene Name:
GSTM3
Uniprot ID:
P21266
Molecular Weight:
26559.32 Da
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. [17372252 ]
  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. [17617661 ]
Target Details
27. Glutathione S-transferase P
General Function:
S-nitrosoglutathione binding
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Gene Name:
GSTP1
Uniprot ID:
P09211
Molecular Weight:
23355.625 Da
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. [17465221 ]
  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. [17517071 ]
Target Details
28. Glutathione S-transferase omega-1
General Function:
Oxidoreductase activity
Specific Function:
Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.
Gene Name:
GSTO1
Uniprot ID:
P78417
Molecular Weight:
27565.6 Da
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. [17537474 ]
  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. [17617905 ]
Target Details
29. Glutathione peroxidase 3
General Function:
Transcription factor binding
Specific Function:
Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.
Gene Name:
GPX3
Uniprot ID:
P22352
Molecular Weight:
25552.185 Da
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. [17558897 ]
  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. [17578749 ]
Target Details
30. Lactoylglutathione lyase
General Function:
Zinc ion binding
Specific Function:
Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B. Required for normal osteoclastogenesis.
Gene Name:
GLO1
Uniprot ID:
Q04760
Molecular Weight:
20777.515 Da
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 metabolism in glomeruli of db/db diabetic mice. Am J Physiol Renal Physiol. 2007 Oct;293(4):F1157-65. Epub 2007 Jul 3. [17609286 ]
  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. [17664277 ]
Target Details
31. Leukotriene C4 synthase
General Function:
Lipid binding
Specific Function:
Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.
Gene Name:
LTC4S
Uniprot ID:
Q16873
Molecular Weight:
16566.465 Da
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. [17632546 ]
  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. [17632548 ]
Target Details
32. Microsomal glutathione S-transferase 1
General Function:
Glutathione transferase activity
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Has a wide substrate specificity.
Gene Name:
MGST1
Uniprot ID:
P10620
Molecular Weight:
17598.45 Da
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. [17306223 ]
  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. [17297922 ]
Target Details
33. Probable glutathione peroxidase 8
General Function:
Peroxidase activity
Specific Function:
Not Available
Gene Name:
GPX8
Uniprot ID:
Q8TED1
Molecular Weight:
23880.83 Da
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. [17139284 ]
  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. [17016423 ]
Target Details
34. Thioredoxin domain-containing protein 12
General Function:
Protein-disulfide reductase (glutathione) activity
Specific Function:
Possesses significant protein thiol-disulfide oxidase activity.
Gene Name:
TXNDC12
Uniprot ID:
O95881
Molecular Weight:
19205.615 Da
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. [17139284 ]
  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. [17016423 ]
Target Details
35. Cytochrome P450 3A4
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Davydov DR, Davydova NY, Tsalkova TN, Halpert JR: Effect of glutathione on homo- and heterotropic cooperativity in cytochrome P450 3A4. Arch Biochem Biophys. 2008 Mar 15;471(2):134-45. doi: 10.1016/j.abb.2008.01.001. Epub 2008 Jan 11. [18206979 ]
Target Details
36. Epididymal secretory glutathione peroxidase
General Function:
Glutathione peroxidase activity
Specific Function:
Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-like protective system against peroxide damage in sperm membrane lipids.
Gene Name:
GPX5
Uniprot ID:
O75715
Molecular Weight:
25202.14 Da
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. [17531267 ]
Target Details
37. Glutathione S-transferase A4
General Function:
Protein homodimerization activity
Specific Function:
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).
Gene Name:
GSTA4
Uniprot ID:
O15217
Molecular Weight:
25703.905 Da
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 Dec;21(8):1365-72. Epub 2007 Apr 27. [17553661 ]
Target Details
38. Glutathione peroxidase 2
General Function:
Glutathione peroxidase activity
Specific Function:
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.
Gene Name:
GPX2
Uniprot ID:
P18283
Molecular Weight:
21953.835 Da
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. [17510403 ]
Target Details
39. Glutathione peroxidase 7
General Function:
Peroxidase activity
Specific Function:
It protects esophageal epithelia from hydrogen peroxide-induced oxidative stress. It suppresses acidic bile acid-induced reactive oxigen species (ROS) and protects against oxidative DNA damage and double-strand breaks.
Gene Name:
GPX7
Uniprot ID:
Q96SL4
Molecular Weight:
20995.88 Da
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. 2008 Feb;19(2):118-28. Epub 2007 Jun 27. [17588737 ]
Target Details
40. Matrix metalloproteinase-9
General Function:
Zinc ion binding
Specific Function:
May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
Gene Name:
MMP9
Uniprot ID:
P14780
Molecular Weight:
78457.51 Da
References
  1. Pei P, Horan MP, Hille R, Hemann CF, Schwendeman SP, Mallery SR: Reduced nonprotein thiols inhibit activation and function of MMP-9: implications for chemoprevention. Free Radic Biol Med. 2006 Oct 15;41(8):1315-24. Epub 2006 Jul 15. [17015178 ]
Target Details
41. Microsomal glutathione S-transferase 2
General Function:
Leukotriene-c4 synthase activity
Specific Function:
Can catalyze the production of LTC4 from LTA4 and reduced glutathione. Can catalyze the conjugation of 1-chloro-2,4-dinitrobenzene with reduced glutathione.
Gene Name:
MGST2
Uniprot ID:
Q99735
Molecular Weight:
16620.4 Da
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. [17632548 ]
Target Details
42. Microsomal glutathione S-transferase 3
General Function:
Peroxidase activity
Specific Function:
Also functions as a glutathione peroxidase.
Gene Name:
MGST3
Uniprot ID:
O14880
Molecular Weight:
16516.185 Da
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. [17632548 ]