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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-12-01 23:17:10 UTC
HMDB IDHMDB00267
Secondary Accession NumbersNone
Metabolite Identification
Common NamePyroglutamic acid
DescriptionPyroglutamic acid is a cyclized derivative of L-glutamic acid. It is an uncommon amino acid derivative in which the free amino group of glutamic acid cyclizes to form a lactam. It is formed nonenzymatically from glutamate, glutamine, and gamma-glutamylated peptides, but it can also be produced by the action of gamma-glutamylcyclotransferase on an L-amino acid. Elevated blood levels may be associated with problems of glutamine or glutathione metabolism. This compound is found in substantial amounts in brain tissue and other tissue in bound form, especially skin. Also present in plant tissues. It is sold, over the counter, as a "smart drug" for improving blood circulation in the brain.
Structure
Thumb
Synonyms
  1. (-)-2-Pyrrolidone-5-carboxylate
  2. (-)-2-Pyrrolidone-5-carboxylic acid
  3. (-)-Pyroglutamate
  4. (-)-Pyroglutamic acid
  5. (5S)-2-Oxopyrrolidine-5-carboxylate
  6. (5S)-2-Oxopyrrolidine-5-carboxylic acid
  7. (S)-(-)-2-Pyrrolidone-5-carboxylate
  8. (S)-(-)-2-Pyrrolidone-5-carboxylic acid
  9. (S)-(-)-g-Butyrolactam-g-carboxylate
  10. (S)-(-)-g-Butyrolactam-g-carboxylic acid
  11. (S)-(-)-gamma-Butyrolactam-gamma-carboxylate
  12. (S)-(-)-gamma-Butyrolactam-gamma-carboxylic acid
  13. (S)-2-Pyrrolidone-5-carboxylate
  14. (S)-2-Pyrrolidone-5-carboxylic acid
  15. (S)-5-Oxo-2-pyrrolidinecarboxylate
  16. (S)-5-Oxo-2-pyrrolidinecarboxylic acid
  17. (S)-Pyroglutamate
  18. (S)-Pyroglutamic acid
  19. 2-L-Pyrrolidone-5-carboxylate
  20. 2-L-Pyrrolidone-5-carboxylic acid
  21. 2-Oxopyrrolidine-5(S)-carboxylate
  22. 2-Oxopyrrolidine-5(S)-carboxylic acid
  23. 2-Pyrrolidinone-5-carboxylate
  24. 2-Pyrrolidinone-5-carboxylic acid
  25. 5-Carboxy-2-pyrrolidinone
  26. 5-L-Oxoproline
  27. 5-Oxo-L-proline
  28. 5-Oxoproline
  29. 5-Pyrrolidinone-2-carboxylate
  30. 5-Pyrrolidinone-2-carboxylic acid
  31. Ajidew A 100
  32. Glutimate
  33. Glutimic acid
  34. Glutiminate
  35. Glutiminic acid
  36. L-2-Pyrrolidone-5-carboxylate
  37. L-2-Pyrrolidone-5-carboxylic acid
  38. L-5-Carboxy-2-pyrrolidinone
  39. L-5-Oxo-2-pyrrolidinecarboxylate
  40. L-5-Oxo-2-pyrrolidinecarboxylic acid
  41. L-5-Oxoproline
  42. L-Glutamic acid g-lactam
  43. L-Glutimate
  44. L-Glutimic acid
  45. L-Glutiminate
  46. L-Glutiminic acid
  47. L-Pyroglutamate
  48. L-Pyroglutamic acid
  49. L-Pyrrolidinonecarboxylate
  50. L-Pyrrolidinonecarboxylic acid
  51. L-Pyrrolidonecarboxylate
  52. L-Pyrrolidonecarboxylic acid
  53. Oxoproline
  54. Oxopyrrolidinecarboxylate
  55. Oxopyrrolidinecarboxylic acid
  56. Pidolate
  57. Pidolic acid
  58. Pidolidone
  59. Pyroglutamate
  60. Pyroglutamic acid
  61. Pyrrolidinonecarboxylate
  62. Pyrrolidinonecarboxylic acid
  63. Pyrrolidone-5-carboxylate
  64. Pyrrolidone-5-carboxylic acid
  65. Pyrrolidonecarboxylic acid
Chemical FormulaC5H7NO3
Average Molecular Weight129.114
Monoisotopic Molecular Weight129.042593095
IUPAC Name(2S)-5-oxopyrrolidine-2-carboxylic acid
Traditional Namepyroglutamic acid
CAS Registry Number98-79-3
SMILES
OC(=O)[C@@H]1CCC(=O)N1
InChI Identifier
InChI=1S/C5H7NO3/c7-4-2-1-3(6-4)5(8)9/h3H,1-2H2,(H,6,7)(H,8,9)/t3-/m0/s1
InChI KeyODHCTXKNWHHXJC-VKHMYHEASA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAliphatic Heteromonocyclic Compounds
ClassPyrrolidines
Sub ClassPyrrolidine Carboxylic Acids and Derivatives
Other Descriptors
  • 5-oxoproline(ChEBI)
  • Aliphatic Heteromonocyclic Compounds
  • Other amino acids(KEGG)
  • Oxoprolines
Substituents
  • Carboxamide Group
  • Carboxylic Acid
  • Lactam
  • Pyrrolidone
  • Secondary Carboxylic Acid Amide
Direct ParentPyrrolidine Carboxylic Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Glutathione metabolism
  • Essential amino acid
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility476.0 mg/mL at 13 °CNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility151.0ALOGPS
logP-1ALOGPS
logP-0.89ChemAxon
logS0.07ALOGPS
pKa (Strongest Acidic)3.61ChemAxon
pKa (Strongest Basic)-1.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.4 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity28.09 m3·mol-1ChemAxon
Polarizability11.56 Å3ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Brain
  • Prostate
  • Skin
Pathways
NameSMPDB LinkKEGG Link
Glutathione MetabolismSMP00015map00480
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified19.5 +/- 3.7 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified87.00 (13.00-161.00) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified47 +/- 30 uMNot SpecifiedBothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified41.0 +/- 31.0 uMAdult (>18 years old)Not SpecifiedNormal details
FecesDetected but not QuantifiedNot ApplicableInfant (0-1 year old)Both
Normal
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot ApplicableNot SpecifiedNot Specified
Normal
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot ApplicableNot SpecifiedNot Specified
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified30.19 +/- 31.32 uMAdult (>18 years old)BothNormal
    • Dame, ZT. et al. ...
details
UrineDetected and Quantified28.8 (3.4-54.2) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified20.7 (10.2-32.6) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified14.0 +/- 7.2 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified7.3 (0.1-29.3) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified24.1 (3.4-54.2) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified5.3 (2.9-10.4) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified3.1 (1.9-11.3) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified18.6 (4.5-24.9) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified3.5 (3.00-4.00) uMChildren (1-13 years old)BothGlutathione synthetase deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified2326.0 uMAdult (>18 years old)BothPyroglutamic aciduria details
FecesDetected but not QuantifiedNot ApplicableNot SpecifiedNot Specified
Cryptosporidium infection
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Irritable bowel syndrome
details
UrineDetected and Quantified3500.0 (1000.0-6000.0) umol/mmol creatinineChildren (1-13 years old)Both5-Oxoprolinase Deficiency details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothAutosomal dominant polycystic kidney disease (ADPKD) details
UrineDetected and Quantified17000.00 (4000.00-30000.00) umol/mmol creatinineChildren (1-13 years old)BothGlutathione synthetase deficiency details
UrineDetected and Quantified1.9 umol/mmol creatinineAdult (>18 years old)BothPyroglutamic aciduria details
Associated Disorders and Diseases
Disease References
Glutathione synthetase deficiency
  1. Jellum E, Stokke O, Eldjarn L: Combined use of gas chromatography, mass spectrometry, and computer in diagnosis and studies of metabolic disorders. Clin Chem. 1972 Aug;18(8):800-9. Pubmed: 4557757
  2. Wevers RA, Engelke U, Heerschap A: High-resolution 1H-NMR spectroscopy of blood plasma for metabolic studies. Clin Chem. 1994 Jul;40(7 Pt 1):1245-50. Pubmed: 8013094
  3. MetaGene
5-oxoprolinase deficiency
  1. MetaGene
Associated OMIM IDs
  • 266130 (Glutathione synthetase deficiency)
  • 260005 (5-oxoprolinase deficiency)
DrugBank IDDB03088
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB014506
KNApSAcK IDC00007403
Chemspider ID7127
KEGG Compound IDC01879
BioCyc IDCPD-589
BiGG ID1800372
Wikipedia LinkPyroglutamic acid
NuGOwiki LinkHMDB00267
Metagene LinkHMDB00267
METLIN ID3251
PubChem Compound7405
PDB IDPCA
ChEBI ID18183
References
Synthesis ReferencePumpor, Ksenia; Boettcher, Christoph; Fehn, Susanna; Burger, Klaus. Hexafluoroacetone as protecting and activating reagent: an efficient strategy for activation of pyroglutamic acid and homologs.Heterocycles (2003), 61 259-269.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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. Pubmed: 19212411
  2. Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. Pubmed: 8087979
  3. Hoffmann GF, Meier-Augenstein W, Stockler S, Surtees R, Rating D, Nyhan WL: Physiology and pathophysiology of organic acids in cerebrospinal fluid. J Inherit Metab Dis. 1993;16(4):648-69. Pubmed: 8412012
  4. Jellum E, Stokke O, Eldjarn L: Combined use of gas chromatography, mass spectrometry, and computer in diagnosis and studies of metabolic disorders. Clin Chem. 1972 Aug;18(8):800-9. Pubmed: 4557757
  5. Wevers RA, Engelke U, Heerschap A: High-resolution 1H-NMR spectroscopy of blood plasma for metabolic studies. Clin Chem. 1994 Jul;40(7 Pt 1):1245-50. Pubmed: 8013094
  6. Manning NJ, Davies NP, Olpin SE, Carpenter KH, Smith MF, Pollitt RJ, Duncan SL, Larsson A, Carlsson B: Prenatal diagnosis of glutathione synthase deficiency. Prenat Diagn. 1994 Jun;14(6):475-8. Pubmed: 7937585
  7. Caspers PJ, Lucassen GW, Carter EA, Bruining HA, Puppels GJ: In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles. J Invest Dermatol. 2001 Mar;116(3):434-42. Pubmed: 11231318
  8. Hussain Z, Lannigan R, Stoakes L: A new approach for presumptive identification of clinically important streptococci. Zentralbl Bakteriol Mikrobiol Hyg [A]. 1984 Oct;258(1):74-9. Pubmed: 6441390
  9. Creer MH, Lau BW, Jones JD, Chan KM: Pyroglutamic acidemia in an adult patient. Clin Chem. 1989 Apr;35(4):684-6. Pubmed: 2702756
  10. Hammond JW, Potter M, Truscott R, Wilcken B: gamma-Glutamylglutamine identified in plasma and cerebrospinal fluid from hyperammonaemic patients. Clin Chim Acta. 1990 Dec 24;194(2-3):173-83. Pubmed: 2093471
  11. Uhlhaas S, Lange H: Striatal deficiency of L-pyroglutamic acid in Huntington's disease is accompanied by increased plasma levels. Brain Res. 1988 Aug 2;457(1):196-9. Pubmed: 2971422
  12. Croal BL, Glen AC, Kelly CJ, Logan RW: Transient 5-oxoprolinuria (pyroglutamic aciduria) with systemic acidosis in an adult receiving antibiotic therapy. Clin Chem. 1998 Feb;44(2):336-40. Pubmed: 9474033
  13. Winslow JW, Shih A, Bourell JH, Weiss G, Reed B, Stults JT, Goldsmith LT: Human seminal relaxin is a product of the same gene as human luteal relaxin. Endocrinology. 1992 May;130(5):2660-8. Pubmed: 1572287
  14. Erasmus E, Mienie LJ, de Vries WN, de Wet WJ, Carlsson B, Larsson A: Prenatal analysis in two suspected cases of glutathione synthetase deficiency. J Inherit Metab Dis. 1993;16(5):837-43. Pubmed: 8295398

Enzymes

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 hydrolase activity
Specific function:
Catalyzes the cleavage of 5-oxo-L-proline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate.
Gene Name:
OPLAH
Uniprot ID:
O14841
Molecular weight:
137456.195
Reactions
Adenosine triphosphate + Pyroglutamic acid + Water → ADP + Phosphoric acid + L-Glutamic aciddetails
General function:
Involved in nucleic acid binding
Specific function:
May function as a tRNA-specific ribonuclease that binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus, thereby promoting the endothelial invasiveness necessary for blood vessel formation. Angiogenin induces vascularization of normal and malignant tissues. Abolishes protein synthesis by specifically hydrolyzing cellular tRNAs
Gene Name:
ANG
Uniprot ID:
P03950
Molecular weight:
16549.9
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
General function:
Involved in antigen binding
Specific function:
Not Available
Gene Name:
Not Available
Uniprot ID:
P01709
Molecular weight:
11557.5
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
AMY1A
Uniprot ID:
P04745
Molecular weight:
Not Available
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
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
AMY2A
Uniprot ID:
P04746
Molecular weight:
Not Available
General function:
Involved in growth factor activity
Specific function:
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth
Gene Name:
VEGFA
Uniprot ID:
P15692
Molecular weight:
27042.2
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
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
AMY2B
Uniprot ID:
P19961
Molecular weight:
Not Available
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
General function:
Involved in neuropeptide signaling pathway
Specific function:
Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity
Gene Name:
HCRT
Uniprot ID:
O43612
Molecular weight:
13362.5
References
  1. 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
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
(5-L-Glutamyl)-L-amino acid → Pyroglutamic acid + L-Amino aciddetails
General function:
Involved in antigen binding
Specific function:
Not Available
Gene Name:
IGLC1
Uniprot ID:
P0CG04
Molecular weight:
11347.6
References
  1. 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