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Showing metabocard for gamma-Glutamylcysteine (HMDB0001049)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (4) Show 4 proteinsXML
enzymes (4) Show 4 proteins
Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-02-26 21:22:53 UTC
HMDB IDHMDB0001049
Secondary Accession Numbers
  • HMDB0029146
  • HMDB01049
  • HMDB29146
Metabolite Identification
Common Namegamma-Glutamylcysteine
Descriptiongamma-Glutamylcysteine is a dipeptide composed of gamma-glutamate and cysteine, and is a proteolytic breakdown product of larger proteins. It belongs to the family of N-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom. gamma-Glutamylcysteine is an incomplete breakdown product of protein digestion or protein catabolism. Some dipeptides are known to have physiological or cell-signaling effects although most are simply short-lived intermediates on their way to specific amino acid degradation pathways following further proteolysis. gamma-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 the glutamate metabolism pathway (KEGG).
Structure
Data?1582752173
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
γ-Glu-CysHMDB, Generator
γ-L-Glu-L-CysHMDB
γ-GlutamylcysteineHMDB, Generator
γ-L-Glutamyl-L-cysteineHMDB, Generator
L-γ-Glutamyl-L-cysteineHMDB
N-γ-GlutamylcysteineHMDB
N-L-γ-GlutamylcysteineHMDB
N-L-γ-Glutamyl-L-cysteineHMDB
gamma-Glu-CysHMDB, ChEBI
gamma-L-Glu-L-CysHMDB
gamma-L-Glutamyl-L-cysteineHMDB, ChEBI
L-gamma-Glutamyl-L-cysteineHMDB
N-gamma-GlutamylcysteineHMDB
N-L-gamma-GlutamylcysteineHMDB
N-L-gamma-Glutamyl-L-cysteineHMDB
gamma-GlutamylcysteineHMDB
5-L-Glutamyl-L-cysteineChEBI
L-gamma-GlutamylcysteineChEBI
g-GlutamylcysteineGenerator
g-Glu-CysGenerator
g-L-Glutamyl-L-cysteineGenerator
L-g-GlutamylcysteineGenerator
L-γ-glutamylcysteineGenerator
5-L-GlutamylcysteineHMDB
H-gamma-Glu-Cys-OHHMDB
L-g-Glutamyl-L-cysteineHMDB
N-γ-L-Glutamyl-L-cysteineHMDB
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 KeyRITKHVBHSGLULN-WHFBIAKZSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as n-acyl-alpha amino acids. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids
Alternative Parents
Substituents
  • N-acyl-alpha-amino acid
  • Cysteine or derivatives
  • Alpha-amino acid
  • L-alpha-amino acid
  • Fatty acid
  • Dicarboxylic 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
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organosulfur compound
  • Primary aliphatic amine
  • Primary amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Carbonyl group
  • Amine
  • Organic oxygen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

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 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity56.31 m³·mol⁻¹ChemAxon
Polarizability23.36 ųChemAxon
Number of Rings0ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-054t-1920100000-5ce9a082971db6d9e2e9Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-054t-1920100000-5ce9a082971db6d9e2e9Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-053u-9630000000-344be03dbe2132b00c88Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00b9-8494000000-88b1eea1e1badaee084bSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0udi-0090000000-50bd1555ededc1afde80Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0udi-0290000000-385ca433f03af7530f47Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0ue9-5490000000-95d45a9cd2bb6249d3a2Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-001i-9510000000-5f29ca903abe05256c83Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-9510000000-5f29ca903abe05256c83Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000t-1390000000-e723899e4ca71bda7600Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00sj-3960000000-9a2f96ad7d24e7546315Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00e9-9300000000-e14b428bbb5b63d3ae06Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05fr-1790000000-2aaa1344429a2297cc6bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-4920000000-4ad42780853d5599c05bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05fr-9400000000-b67fd0eaf646aa8f47b3Spectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue Locations
  • Fibroblasts
  • Neuron
  • Placenta
  • Prostate
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
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
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedNormal details
UrineDetected and Quantified0.46+/-0.14 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified2.07 +/- 0.12 uMAdult (>18 years old)Both
Schizophrenia		 details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)BothCrohns disease details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)BothUlcerative colitis details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedCrohns disease details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedUlcerative colitis details
FecesDetected but not QuantifiedNot QuantifiedChildren (6 - 18 years old)Not SpecifiedUnclassified IBD 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. [PubMed:25004141 ]
Crohn's disease
  1. Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
Ulcerative colitis
  1. Kolho KL, Pessia A, Jaakkola T, de Vos WM, Velagapudi V: Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2017 Mar 1;11(3):321-334. doi: 10.1093/ecco-jcc/jjw158. [PubMed:27609529 ]
Associated OMIM IDs
DrugBank IDDB03408
Phenol Explorer Compound IDNot Available
FooDB IDFDB003603
KNApSAcK IDC00007507
Chemspider ID110467
KEGG Compound IDC00669
BioCyc IDL-GAMMA-GLUTAMYLCYSTEINE
BiGG ID35655
Wikipedia LinkGamma-Glutamylcysteine
METLIN ID5966
PubChem Compound123938
PDB IDNot Available
ChEBI ID17515
Food Biomarker OntologyNot Available
VMH IDGLUCYS
MarkerDB ID
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. 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. [PubMed:9461289 ]
  2. 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:15796179 ]
  3. 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. [PubMed:12707912 ]
  4. 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. [PubMed:3667817 ]
  5. Andersson A, Isaksson A, Hultberg B: Homocysteine export from erythrocytes and its implication for plasma sampling. Clin Chem. 1992 Jul;38(7):1311-5. [PubMed:1623596 ]
  6. 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. [PubMed:15314090 ]
  7. 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. [PubMed:15702405 ]
  8. 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. [PubMed:8353942 ]
  9. 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. [PubMed:16183645 ]
  10. Levonen AL, Lapatto R, Saksela M, Raivio KO: Expression of gamma-glutamylcysteine synthetase during development. Pediatr Res. 2000 Feb;47(2):266-70. [PubMed:10674357 ]
  11. 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. [PubMed:3938407 ]
  12. 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. [PubMed:15706569 ]
  13. 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. [PubMed:15717202 ]
  14. 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. [PubMed:10328968 ]
  15. 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. doi: 10.1038/nature07762. [PubMed:19212411 ]
  16. Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

Enzymes

Enzyme Details
1. Glutamate--cysteine ligase catalytic subunit
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 + Phosphate + gamma-Glutamylcysteinedetails
Enzyme Details
2. Glutaminyl-peptide cyclotransferase
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
Enzyme Details
3. Glutathione synthetase
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 + Phosphate + 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. [PubMed: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. [PubMed: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. [PubMed:10592235 ]
Enzyme Details
4. Gamma-glutamylcyclotransferase
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