You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-10-12 17:32:03 UTC
HMDB IDHMDB01049
Secondary Accession NumbersNone
Metabolite Identification
Common NameGamma-Glutamylcysteine
DescriptionG-Glutamylcysteine is a product of enzyme glutamate-cysteine ligase [EC 6.3.2.2] and a substrate of enzyme glutathione synthase [EC 6.3.2.3] in glutamate metabolism pathway (KEGG).
Structure
Thumb
Synonyms
ValueSource
5-L-Glutamyl-L-cysteineChEBI
gamma-Glu-cysChEBI
gamma-GlutamylcysteineChEBI
gamma-L-Glutamyl-L-cysteineChEBI
GammaGluCysChEBI
Glu(-cys)ChEBI
L-gamma-GlutamylcysteineChEBI
L-g-Glutamyl-L-cysteineGenerator
L-γ-glutamyl-L-cysteineGenerator
g-Glu-cysGenerator
γ-glu-cysGenerator
g-GlutamylcysteineGenerator
γ-glutamylcysteineGenerator
g-L-Glutamyl-L-cysteineGenerator
γ-L-glutamyl-L-cysteineGenerator
L-g-GlutamylcysteineGenerator
L-γ-glutamylcysteineGenerator
(Des-gly)-glutathioneHMDB
3GCHMDB
5-L-GlutamylcysteineHMDB
H-gamma-Glu-cys-OHHMDB
H-Glu(cys-OH)-OHHMDB
N-(1-Carboxy-2-mercaptoethyl)-L-glutamineHMDB
N-L-gamma-Glutamyl-L-cysteineHMDB
XN-L-g-Glutamyl-glutamineHMDB
XN-L-gamma-Glutamyl-glutamineHMDB
Chemical FormulaC8H14N2O5S
Average Molecular Weight250.272
Monoisotopic Molecular Weight250.062342258
IUPAC Name(2S)-2-amino-4-{[(1R)-1-carboxy-2-sulfanylethyl]carbamoyl}butanoic acid
Traditional Namegamma-glutamylcysteine
CAS Registry Number636-58-8
SMILES
N[C@@H](CCC(=O)N[C@@H](CS)C(O)=O)C(O)=O
InChI Identifier
InChI=1S/C8H14N2O5S/c9-4(7(12)13)1-2-6(11)10-5(3-16)8(14)15/h4-5,16H,1-3,9H2,(H,10,11)(H,12,13)(H,14,15)/t4-,5-/m0/s1
InChI KeyInChIKey=RITKHVBHSGLULN-WHFBIAKZSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as gamma-glutamyl amino acids. These are dipeptides consisting of any C-terminal amino acid having a gamma-glutamyl residue attached at the N alpha-position.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGamma-glutamyl amino acids
Alternative Parents
Substituents
  • Gamma-glutamyl alpha-amino acid
  • N-acyl-aliphatic-alpha amino acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • N-acyl-l-alpha-amino acid
  • L-alpha-amino acid
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Alpha-amino acid
  • Amino fatty acid
  • Fatty acyl
  • Fatty acid
  • N-acyl-amine
  • Fatty amide
  • Dicarboxylic acid or derivatives
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Carboxylic acid
  • Carboxylic acid amide
  • Alkylthiol
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Glutamate metabolism
  • Component of Glutathione metabolism
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility2.62 mg/mLALOGPS
logP-2.5ALOGPS
logP-3.8ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)1.91ChemAxon
pKa (Strongest Basic)9.24ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area129.72 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity56.31 m3·mol-1ChemAxon
Polarizability23.36 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-054t-1920100000-5ce9a082971db6d9e2e9View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0udi-0090000000-50bd1555ededc1afde80View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0udi-0290000000-385ca433f03af7530f47View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0ue9-5490000000-95d45a9cd2bb6249d3a2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-001i-9510000000-5f29ca903abe05256c83View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Fibroblasts
  • Neuron
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
2-Hydroxyglutric Aciduria (D And L Form)SMP00136Not Available
4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase DeficiencySMP00243Not Available
5-oxoprolinase deficiencySMP00500Not Available
5-OxoprolinuriaSMP00143Not Available
Beta-mercaptolactate-cysteine disulfiduriaSMP00499Not Available
Cysteine MetabolismSMP00013map00270
Cystinosis, ocular nonnephropathicSMP00722Not Available
Gamma-glutamyl-transpeptidase deficiencySMP00501Not Available
Gamma-Glutamyltransferase DeficiencySMP00183Not Available
Glutamate MetabolismSMP00072map00250
Glutathione MetabolismSMP00015map00480
Glutathione Synthetase DeficiencySMP00337Not Available
HomocarnosinosisSMP00385Not Available
Hyperinsulinism-Hyperammonemia SyndromeSMP00339Not Available
Succinic semialdehyde dehydrogenase deficiencySMP00567Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified3.05 +/- 0.11 uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified25.0 +/- 8.0 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified1.9 +/- 0.5 uMAdult (>18 years old)MaleNormal details
UrineDetected and Quantified0.46+/-0.14 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified2.07 +/- 0.12 uMAdult (>18 years old)Both
Schizophrenia
details
Associated Disorders and Diseases
Disease References
Schizophrenia
  1. Fukushima T, Iizuka H, Yokota A, Suzuki T, Ohno C, Kono Y, Nishikiori M, Seki A, Ichiba H, Watanabe Y, Hongo S, Utsunomiya M, Nakatani M, Sadamoto K, Yoshio T: Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients. PLoS One. 2014 Jul 8;9(7):e101652. doi: 10.1371/journal.pone.0101652. eCollection 2014. [25004141 ]
Associated OMIM IDs
DrugBank IDDB03408
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB003603
KNApSAcK IDNot Available
Chemspider ID110467
KEGG Compound IDC00669
BioCyc IDL-GAMMA-GLUTAMYLCYSTEINE
BiGG ID35655
Wikipedia LinkNot Available
NuGOwiki LinkHMDB01049
Metagene LinkHMDB01049
METLIN ID5966
PubChem Compound123938
PDB ID3GC
ChEBI ID17515
References
Synthesis ReferenceBridge, Wallace John; Zarka, Martin Hani. Enzymic production of g-glutamylcysteine. PCT Int. Appl. (2006), 76pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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 ]
  2. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. [19212411 ]
  3. Andersson A, Isaksson A, Brattstrom L, Hultberg B: Homocysteine and other thiols determined in plasma by HPLC and thiol-specific postcolumn derivatization. Clin Chem. 1993 Aug;39(8):1590-7. [8353942 ]
  4. Iida M, Yasuhara T, Mochizuki H, Takakura H, Yanagisawa T, Kubo H: Two Japanese brothers with hereditary gamma-glutamyl transpeptidase deficiency. J Inherit Metab Dis. 2005;28(1):49-55. [15702405 ]
  5. Lochman P, Adam T, Friedecky D, Hlidkova E, Skopkova Z: High-throughput capillary electrophoretic method for determination of total aminothiols in plasma and urine. Electrophoresis. 2003 Apr;24(7-8):1200-7. [12707912 ]
  6. Atamna H, Ginsburg H: The malaria parasite supplies glutathione to its host cell--investigation of glutathione transport and metabolism in human erythrocytes infected with Plasmodium falciparum. Eur J Biochem. 1997 Dec 15;250(3):670-9. [9461289 ]
  7. Martensson J: Method for determination of free and total glutathione and gamma-glutamylcysteine concentrations in human leukocytes and plasma. J Chromatogr. 1987 Sep 4;420(1):152-7. [3667817 ]
  8. Andersson A, Isaksson A, Hultberg B: Homocysteine export from erythrocytes and its implication for plasma sampling. Clin Chem. 1992 Jul;38(7):1311-5. [1623596 ]
  9. Kaarteenaho-Wiik R, Kinnula VL: Distribution of antioxidant enzymes in developing human lung, respiratory distress syndrome, and bronchopulmonary dysplasia. J Histochem Cytochem. 2004 Sep;52(9):1231-40. [15314090 ]
  10. Diaz-Hernandez JI, Almeida A, Delgado-Esteban M, Fernandez E, Bolanos JP: Knockdown of glutamate-cysteine ligase by small hairpin RNA reveals that both catalytic and modulatory subunits are essential for the survival of primary neurons. J Biol Chem. 2005 Nov 25;280(47):38992-9001. Epub 2005 Sep 23. [16183645 ]
  11. Levonen AL, Lapatto R, Saksela M, Raivio KO: Expression of gamma-glutamylcysteine synthetase during development. Pediatr Res. 2000 Feb;47(2):266-70. [10674357 ]
  12. Martensson J, Kagedal B, Larsson A: Sulphur amino-acid degradation in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria). Eur J Clin Invest. 1985 Dec;15(6):371-4. [3938407 ]
  13. Zinellu A, Sotgia S, Posadino AM, Pasciu V, Perino MG, Tadolini B, Deiana L, Carru C: Highly sensitive simultaneous detection of cultured cellular thiols by laser induced fluorescence-capillary electrophoresis. Electrophoresis. 2005 Mar;26(6):1063-70. [15706569 ]
  14. Njalsson R, Ristoff E, Carlsson K, Winkler A, Larsson A, Norgren S: Genotype, enzyme activity, glutathione level, and clinical phenotype in patients with glutathione synthetase deficiency. Hum Genet. 2005 Apr;116(5):384-9. Epub 2005 Feb 17. [15717202 ]
  15. Lou MF, Dickerson JE Jr, Tung WH, Wolfe JK, Chylack LT Jr: Correlation of nuclear color and opalescence with protein S-thiolation in human lenses. Exp Eye Res. 1999 May;68(5):547-52. [10328968 ]

Enzymes

General function:
Involved in glutamate-cysteine ligase activity
Specific function:
Not Available
Gene Name:
GCLC
Uniprot ID:
P48506
Molecular weight:
68629.42
Reactions
Adenosine triphosphate + L-Glutamic acid + L-Cysteine → ADP + Phosphoric acid + Gamma-Glutamylcysteinedetails
General function:
Involved in peptidase activity
Specific function:
Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-beta-amyloid. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides.
Gene Name:
QPCT
Uniprot ID:
Q16769
Molecular weight:
40876.14
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
GSS
Uniprot ID:
P48637
Molecular weight:
52384.325
Reactions
Adenosine triphosphate + Gamma-Glutamylcysteine + Glycine → ADP + Phosphoric acid + Glutathionedetails
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. 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 ]
General function:
Involved in acyltransferase activity
Specific function:
Catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides and may play a significant role in glutathione homeostasis. Induces release of cytochrome c from mitochondria with resultant induction of apoptosis.
Gene Name:
GGCT
Uniprot ID:
O75223
Molecular weight:
19091.635
Reactions
Gamma-Glutamylcysteine → Pyroglutamic acid + L-Cysteinedetails