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Record Information
Version3.6
Creation Date2006-08-13 06:19:17 UTC
Update Date2016-02-11 01:06:27 UTC
HMDB IDHMDB03869
Secondary Accession NumbersNone
Metabolite Identification
Common NameEpsilon-(gamma-Glutamyl)-lysine
DescriptionIn non-diabetic kidney scarring the protein crosslinking enzyme tissue transglutaminase (tTg) has been implicated in the process by the formation of increased epsilon-(gamma-glutamyl)lysine bonds between ECM components in both experimental and human disease. Changes in tTg and epsilon-(gamma-glutamyl)lysine occur in human Diabetic nephropathy as well, the leading cause of chronic kidney failure. (PMID 15292688 ). In Parkinson's disease (PD), conformational changes in the alpha-synuclein monomer precede the formation of Lewy bodies. Both tTG and its substrate-characteristic N(epsilon)-(gamma-glutamyl)-lysine crosslink are increased in PD nigral dopamine neurons. (PMID 15001552 ). Expression of tissue transglutaminase (tTgase) and epsilon-(gamma-glutamyl)-lysine was present in all scarring of the blebs sites, being the main cause of failure in glaucoma filtration surgery. Transglutaminases are calcium-dependent enzymes that catalyze the posttranslational modification of proteins through an acyl transfer reaction between the gamma-carboxamide group of a peptide-bound glutaminyl residue and various amines. Covalent cross-linking using epsilon-(gamma-glutamyl)-lysine bonds is stable and resistant to enzymatic, chemical, and mechanical disruption. (PMID: 16936095 ).
Structure
Thumb
Synonyms
ValueSource
epsilon-(gamma-Glu)-lysHMDB
epsilon-(gamma-Glutamyl)lysineHMDB
epsilon-(gamma-Glutamyl)lysine isodipeptideHMDB
epsilon-(gamma-L-Glutamyl)-L-lysineHMDB
N(6)-L-gamma-Glutamyl-L-lysineHMDB
N(epsilon)-(gamma-Glutamyl)-lysineHMDB
Chemical FormulaC11H21N3O5
Average Molecular Weight275.3015
Monoisotopic Molecular Weight275.148120797
IUPAC Name(2S)-2-amino-6-[(4S)-4-amino-4-carboxybutanamido]hexanoic acid
Traditional NameN(6)-L-gamma-glutamyl-L-lysine
CAS Registry Number17105-15-6
SMILES
N[C@@H](CCCCNC(=O)CC[C@H](N)C(O)=O)C(O)=O
InChI Identifier
InChI=1S/C11H21N3O5/c12-7(10(16)17)3-1-2-6-14-9(15)5-4-8(13)11(18)19/h7-8H,1-6,12-13H2,(H,14,15)(H,16,17)(H,18,19)/t7-,8-/m0/s1
InChI KeyInChIKey=JPKNLFVGUZRHOB-YUMQZZPRSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentL-alpha-amino acids
Alternative Parents
Substituents
  • L-alpha-amino acid
  • Medium-chain fatty 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
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locationsNot Available
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 Solubility4.27 mg/mLALOGPS
logP-4ALOGPS
logP-6.1ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)1.94ChemAxon
pKa (Strongest Basic)9.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area155.74 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity65.9 m3·mol-1ChemAxon
Polarizability28.48 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.1629 +/- 0.0392 uMElderly (>65 years old)BothAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.70 (0.66-0.74) uMAdult (>18 years old)Not SpecifiedHuntington's disease details
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  1. Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10. [17031479 ]
Huntington's disease
  1. Jeitner TM, Bogdanov MB, Matson WR, Daikhin Y, Yudkoff M, Folk JE, Steinman L, Browne SE, Beal MF, Blass JP, Cooper AJ: N(epsilon)-(gamma-L-glutamyl)-L-lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington's disease. J Neurochem. 2001 Dec;79(5):1109-12. [11739625 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023239
KNApSAcK IDNot Available
Chemspider ID5378717
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB03869
Metagene LinkHMDB03869
METLIN IDNot Available
PubChem Compound7015684
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Jeitner TM, Bogdanov MB, Matson WR, Daikhin Y, Yudkoff M, Folk JE, Steinman L, Browne SE, Beal MF, Blass JP, Cooper AJ: N(epsilon)-(gamma-L-glutamyl)-L-lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington's disease. J Neurochem. 2001 Dec;79(5):1109-12. [11739625 ]
  2. El Nahas AM, Abo-Zenah H, Skill NJ, Bex S, Wild G, Griffin M, Johnson TS: Elevated epsilon-(gamma-glutamyl)lysine in human diabetic nephropathy results from increased expression and cellular release of tissue transglutaminase. Nephron Clin Pract. 2004;97(3):c108-17. [15292688 ]
  3. Andringa G, Lam KY, Chegary M, Wang X, Chase TN, Bennett MC: Tissue transglutaminase catalyzes the formation of alpha-synuclein crosslinks in Parkinson's disease. FASEB J. 2004 May;18(7):932-4. Epub 2004 Mar 4. [15001552 ]
  4. Priglinger SG, Alge CS, Kook D, Thiel M, Schumann R, Eibl K, Yu A, Neubauer AS, Kampik A, Welge-Lussen U: Potential role of tissue transglutaminase in glaucoma filtering surgery. Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3835-45. [16936095 ]