ContaminantDB: Pyroglutamic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (16)XML

Record Information

Version

1.0

Creation Date

2014-08-29 06:11:12 UTC

Update Date

2026-05-14 17:48:02 UTC

Accession Number

CHEM003230

Identification

Common Name

Pyroglutamic acid

Class

Small Molecule

Description

Pyroglutamic acid, or 5-oxoproline, 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.

Contaminant Sources

FooDB Chemicals
HMDB Contaminants - Feces
HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Animal Toxin
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(-)-2-Pyrrolidone-5-carboxylic acid	ChEBI
(S)-(-)-2-Pyrrolidone-5-carboxylic acid	ChEBI
(S)-Pyroglutamic acid	ChEBI
5-Pyrrolidone-2-carboxylic acid	ChEBI
L-5-Pyrrolidone-2-carboxylic acid	ChEBI
L-Pyroglutamic acid	ChEBI
Pidolic acid	ChEBI
Pyroglutamate	ChEBI
5-oxo-L-Proline	Kegg
(-)-2-Pyrrolidone-5-carboxylate	Generator
(S)-(-)-2-Pyrrolidone-5-carboxylate	Generator
(S)-Pyroglutamate	Generator
5-Pyrrolidone-2-carboxylate	Generator
L-5-Pyrrolidone-2-carboxylate	Generator
L-Pyroglutamate	Generator
Pidolate	Generator
(-)-Pyroglutamate	HMDB
(-)-Pyroglutamic acid	HMDB
(5S)-2-Oxopyrrolidine-5-carboxylate	HMDB
(5S)-2-Oxopyrrolidine-5-carboxylic acid	HMDB
(S)-(-)-g-Butyrolactam-g-carboxylate	HMDB
(S)-(-)-g-Butyrolactam-g-carboxylic acid	HMDB
(S)-(-)-gamma-Butyrolactam-gamma-carboxylate	HMDB
(S)-(-)-gamma-Butyrolactam-gamma-carboxylic acid	HMDB
(S)-2-Pyrrolidone-5-carboxylate	HMDB
(S)-2-Pyrrolidone-5-carboxylic acid	HMDB
(S)-5-oxo-2-Pyrrolidinecarboxylate	HMDB
(S)-5-oxo-2-Pyrrolidinecarboxylic acid	HMDB
2-L-Pyrrolidone-5-carboxylate	HMDB
2-L-Pyrrolidone-5-carboxylic acid	HMDB
2-Oxopyrrolidine-5(S)-carboxylate	HMDB
2-Oxopyrrolidine-5(S)-carboxylic acid	HMDB
2-Pyrrolidinone-5-carboxylate	HMDB
2-Pyrrolidinone-5-carboxylic acid	HMDB
5-Carboxy-2-pyrrolidinone	HMDB
5-L-Oxoproline	HMDB
5-Oxoproline	HMDB
5-Pyrrolidinone-2-carboxylate	HMDB
5-Pyrrolidinone-2-carboxylic acid	HMDB
Ajidew a 100	HMDB
Glutimate	HMDB
Glutimic acid	HMDB
Glutiminate	HMDB
Glutiminic acid	HMDB
L-2-Pyrrolidone-5-carboxylate	HMDB
L-2-Pyrrolidone-5-carboxylic acid	HMDB
L-5-Carboxy-2-pyrrolidinone	HMDB
L-5-oxo-2-Pyrrolidinecarboxylate	HMDB
L-5-oxo-2-Pyrrolidinecarboxylic acid	HMDB
L-5-Oxoproline	HMDB
L-Glutamic acid g-lactam	HMDB
L-Glutimate	HMDB
L-Glutimic acid	HMDB
L-Glutiminate	HMDB
L-Glutiminic acid	HMDB
L-Pyrrolidinonecarboxylate	HMDB
L-Pyrrolidinonecarboxylic acid	HMDB
L-Pyrrolidonecarboxylate	HMDB
L-Pyrrolidonecarboxylic acid	HMDB
Oxoproline	HMDB
Oxopyrrolidinecarboxylate	HMDB
Oxopyrrolidinecarboxylic acid	HMDB
Pidolidone	HMDB
Pyrrolidinonecarboxylate	HMDB
Pyrrolidinonecarboxylic acid	HMDB
Pyrrolidone-5-carboxylate	HMDB
Pyrrolidone-5-carboxylic acid	HMDB
Pyrrolidonecarboxylic acid	HMDB
5-Ketoproline	HMDB
Pidolate, magnesium	HMDB
5-Oxopyrrolidine-2-carboxylic acid	HMDB
Magnesium pidolate	HMDB
2-Pyrrolidone-5-carboxylic acid	HMDB
5-Oxoprolinate	HMDB
PCA	HMDB

Chemical Formula

C₅H₇NO₃

Average Molecular Mass

129.114 g/mol

Monoisotopic Mass

129.043 g/mol

CAS Registry Number

98-79-3

IUPAC Name

(2S)-5-oxopyrrolidine-2-carboxylic acid

Traditional Name

pyroglutamic acid

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 Key

ODHCTXKNWHHXJC-VKHMYHEASA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Alpha amino acids and derivatives

Alternative Parents

Substituents

Alpha-amino acid or derivatives
Pyrroline carboxylic acid
Pyrroline carboxylic acid or derivatives
Pyrroline
Cyclic carboximidic acid
Lactim
Carboxylic acid
Monocarboxylic acid or derivatives
Propargyl-type 1,3-dipolar organic compound
Organic 1,3-dipolar compound
Azacycle
Organoheterocyclic compound
Organopnictogen compound
Organic oxygen compound
Organooxygen compound
Organic oxide
Hydrocarbon derivative
Carbonyl group
Organic nitrogen compound
Organonitrogen compound
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

non-proteinogenic L-alpha-amino acid (CHEBI:18183 )
L-proline derivative (CHEBI:18183 )
5-oxoproline (CHEBI:18183 )
Other amino acids (C01879 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Brain
Prostate
Skin

Pathways

Name	SMPDB Link	KEGG Link
Glutathione Metabolism	SMP00015	map00480
5-Oxoprolinuria	SMP00143	Not Available
5-oxoprolinase deficiency	SMP00500	Not Available
Glutathione Synthetase Deficiency	SMP00337	Not Available
Hawkinsinuria	SMP00190	Not Available
Propionic Acidemia	SMP00236	Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	158°C (316.4°F)
Boiling Point	Not Available
Solubility	476.0 mg/mL at 13°C

Predicted Properties

Property	Value	Source
Water Solubility	151 g/L	ALOGPS
logP	-1	ALOGPS
logP	-0.89	ChemAxon
logS	0.07	ALOGPS
pKa (Strongest Acidic)	3.61	ChemAxon
pKa (Strongest Basic)	-2.2	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	66.4 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	28.09 m³·mol⁻¹	ChemAxon
Polarizability	11.56 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)	splash10-0ab9-8900000000-f79dc90370ba38f587c9	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0ab9-8900000000-f79dc90370ba38f587c9	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0900000000-90fb43273551aeb9b2c4	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a6r-9000000000-130a8f31f82e83c4be07	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-05fr-9200000000-d69b52257404ab658d5b	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-001i-9500000000-ebc64308ec5d5bdb303e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-053r-9000000000-7377cb17491942e9589c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-053u-9000000000-fcab1396867356ebd6ae	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-004i-0900000000-5b0c6536e1b3217b8544	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-004i-0900000000-c30ac0bd264c8007ef92	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-004i-5900000000-ea3a164653e4235716ae	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-0f89-9000000000-f6620738e68f990d0594	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-0udi-9000000000-7937bee2e9a6d6b29cbd	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-004i-0900000000-f20401903b234914b936	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-004i-0900000000-9446bb65e0edd72cfd59	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-0059-7900000000-74eccdeb9f0d5fd17614	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-0f8a-9000000000-8786a9cd5e488192f34d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-0f6t-9000000000-ebcc1ac4acd525218e80	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-01q9-2900000000-754ae9b699ec1b22cd76	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-001i-9300000000-eabb8c4dc0d1111e0431	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-00lr-9100000000-1dd17702aee7e5bce618	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-067i-9000000000-c9669794d3a8746be498	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-014i-9000000000-9e103abb0a6ed890051e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-03e9-3900000000-da8cf252285c1d616586	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-01q9-9400000000-96a7fe5a81188c49d1ba	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-014i-9000000000-356215339a43217dea66	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-02vl-9000000000-ed47ec6e675eb338da19	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-014i-9000000000-f647da344adbdf7bfb1b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-001i-9200000000-0bddc68d58c6fb981d1a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-004i-0900000000-c70c79fa828bbf137ebc	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-001i-9000000000-6c87253da642bb4800df	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

5-Oxoprolinuria develops in moderate to severe cases of glutathione synthetase deficiency. The deficiency in glutathione synthetase leads to the accumulation of γ-glutamylcysteine, which is converted into 5-oxoproline by the action of γ-glutamyl cyclotransferase. The excessive formation of 5-oxoproline exceeds the capacity of 5-oxoprolinase, leading to accumulation of 5-oxoproline in body fluids causing metabolic acidosis and 5-oxoprolinuria. 5-Oxoproline accumulation is thought to be the cause of metabolic acidosis in Hawkinsinuria. 5-Oxoprolinase deficiency also leads to decreased conversion of 5-oxoproline to glutamate, resulting in elevated levels of 5-oxoproline in body fluids. 5-Oxoprolinuria has also been described in patients with urea cycle defects, such as ornithine transcarbamoylase deficiency or homocystinuria. In nephropathic cystinosis 5-oxoprolinuria may occur because of secondary impairment of the γ-glutamyl cycle resulting from decreased availability of free cysteine and can be corrected through cysteamine therapy. Transient 5-oxoprolinuria of unknown cause has been reported in very preterm infants. Limited availability of glycine in malnutrition and pregnancy as well as increased turnover of collagen, fibrinogen and other proteins containing considerable amounts of 5-oxoproline in patients with severe burns or Stevens-Johnson syndrome may lead to 5-oxoprolinuria. In addition, certain drugs, such as paracetamol, vigabatrin or some antibiotics (flucloxacillin, netimicin), are known to induce 5-oxoprolinuria, probably through interaction with the γ-glutamyl cycle. Particular infant formulas and tomato juice may contain modified proteins with increased content of 5-oxoproline. (15)

Metabolism

5-Oxoproline is part of the glutathione metabolism pathway. Degradation of glutathione is initiated by γ-glutamyl transpeptidase, which catalyses the transfer of its γ-glutamyl-group to acceptors. The γ-glutamyl residues are substrates of the γ-glutamyl-cyclotransferase, which converts them to 5-oxoproline and the corresponding amino acids. Conversion of 5-oxoproline to glutamate is catalysed by 5-oxoprolinase. (15)

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

Minimum Risk Level

Not Available

Health Effects

Chronically high levels of pyroglutamic acid are associated with at least 5 inborn errors of metabolism including: 5-Oxoprolinuria, 5-oxoprolinase deficiency, Glutathione Synthetase Deficiency, Hawkinsinuria and Propionic acidemia.

Symptoms

Patients with the moderate variant of glutathione synthetase deficiency usually present during the neonatal period with severe and chronic metabolic acidosis, mild to moderate haemolytic anaemia, jaundice and 5-oxoprolinuria. After the neonatal period, the condition usually stabilises, but patients may become critically ill during infections owing to pronounced acidosis and electrolyte imbalances. Several patients have died during such episodes. In addition to the symptoms mentioned above, patients with severe GS deficiency develop progressive CNS symptoms, e.g. mental retardation, seizures, spasticity, ataxia and intention tremor. In addition, some patients suffer from recurrent severe bacterial infections, which is probably due to defective granulocyte function. Hawkinsinuria is characterised by failure to thrive and metabolic acidosis in infancy. After the 1st year of life the condition appears to be asymptomatic. Early weaning from breastfeeding seems to precipitate the disease; the condition may be asymptomatic in breastfed infants. 5-Oxoprolinase Deficiency: Up to now, eight patients in six different families have been described. The clinical symptoms are inconstant and very heterogeneous, including renal stone formation, enterocolitis, neonatal hypoglycaemia, microcytic anaemia, microcephaly and mental retardation. It remains to be established wheter symptoms in identified patients are merely a coincidence. (15)

Treatment

Glutathione Synthetase Deficiency: The clinical management of GS deficient patients is aimed at correction of acidosis, prevention of haemolytic crises and support of endogenous defence against reactive oxygen species (ROS). In the neonatal period, correction of metabolic acidosis, electrolyte imbalances, treatment of anaemia and excessive hyperbilirubinaemia are of crucial importance. Correction of acidosis can be reached through bicarbonate, citrate or tris-hydroxymethyl aminomethane (THAM). Doses of up to 10 mmol/kg/day, or even higher in episodes of acute infections, may be required. Repeated blood transfusions may be necessary in patients with massive haemolysis. Drugs and foods known to precipitate haemolytic crises in patients with glucose- 6-phosphatase dehydrogenase deficiency should be avoided. Successful treatment with erythropoietin has been reported in one patient. Early supplementation with vitamin E and vitamin C are thought to replenish the lack of GSH as a scavenger of free radicals. Recommended doses are 10 mg/kg/day for vitamin E and 100 mg/kg/day for vitamin C. A longterm follow-up study of 28 patients suggested that early supplementation with both vitamins may prevent CNS damage and improve the long-term clinical outcome in GS-deficient patients. The value of N-acetylcysteine, which is known to protect cells from oxidative stress in vitro, in the treatment of GS deficiency is controversial. It was suggested that the low intracellular GSH concentrations and cysteine availabilty might be increased by N-acetylcysteine. However, supplementation with N-acetylcysteine should not be recommended, because it was shown at least in cultured fibroblasts that patients with GS deficiency accumulate cysteine, which is known to be neurotoxic in excessive amounts. A therapeutic trial with orally administered GSH showed no lasting benefit in two patients with GS deficiency. GSH esters, lipid-soluble preparations which are easily transported into cells where they are converted into GSH, have been tried in animal models of GSH deficiency and in two patients with GS deficiency. However, associated toxic effects due to production of alcohols as a by-product during hydrolysis to release GSH make them of limited use. In vitro studies have shown that addition of S-acetylglutathione to the medium of cultured fibroblasts from patients with GS deficiency normalised intracellular GSH content. Owing to the rarity of the disease and the heterogeneity of the clinical condition the prognosis for individual patients is difficult to predict. Early diagnosis, correction of acidosis and early supplementation with vitamin E and vitamin C appear to be the most important factors regarding the survival and the long-term outcome. Hawkinsinuria: Symptoms in infancy respond to a return to breastfeeding or a diet restricted in tyrosine and phenylalanine along with vitamin C supplementation. The condition is asymptomatic after the 1st year of life, and affected infants are reported to have developed normally. 5-Oxoprolinase Deficiency: No specific treatment has been proposed or tried. (15)

Concentrations

Not Available

External Links

DrugBank ID

DB03088

HMDB ID

HMDB0000267

FooDB ID

FDB014506

Phenol Explorer ID

Not Available

KNApSAcK ID