Pyroglutamic acid

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Pyroglutamic acid
Pyroglutamic acid.svg
Preferred IUPAC name
Systematic IUPAC name
5-Oxopyrrolidine-2-carboxylic acid
Other names
  • 2-Pyrrolidone-5-carboxylic acid
  • Pidolic acid
  • 5-Oxo-proline
3D model (JSmol)
Abbreviations Glp
ECHA InfoCard 100.021.578
EC Number
  • 205-748-3
MeSH Pyrrolidonecarboxylic+acid
RTECS number
  • TW3710000
Molar mass 129.115 g·mol−1
Melting point 184 °C (363 °F; 457 K)
log P -0.89
Acidity (pKa) -1.76, 3.48, 12.76
Basicity (pKb) 15.76, 10.52, 1.24
Isoelectric point 0.94
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but little studied natural amino acid derivative in which the free amino group of glutamic acid or glutamine cyclizes to form a lactam.[1] The names of pyroglutamic acid conjugate base, anion, salts, and esters are pyroglutamate, 5-oxoprolinate, or pidolate.

Formation of pyroglutamic acid from N-terminal glutamine.

It is a metabolite in the glutathione cycle that is converted to glutamate by 5-oxoprolinase. Pyroglutamate is found in many proteins including bacteriorhodopsin. N-terminal glutamic acid and glutamine residues can spontaneously cyclize to become pyroglutamate, or enzymatically converted by glutaminyl cyclases.[2] This is one of several forms of blocked N-termini which present a problem for N-terminal sequencing using Edman chemistry, which requires a free primary amino group not present in pyroglutamic acid. The enzyme pyroglutamate aminopeptidase can restore a free N-terminus by cleaving off the pyroglutamate residue.[3]

Pyroglutamic acid exists as two distinct enantiomers:

  • (2R) or D which happens to be (+) or d
  • (2S) or L which happens to be (–) or l


As first discovered in 1882, pyroglutamic acid can be formed by heating glutamic acid at 180 °C, which results in the loss of a molecule of water. In living cells, it is derived from glutathione through the action of an enzyme, γ-glutamyl cyclotransferase.[1] Pyroglutamic acid may function in glutamate storage, and acts to oppose the action of glutamate, including in the brain.[1] It also acts on the brain's cholinergic system;[4] Amyloid β containing pyroglutamic acid is increased in Alzheimer's disease; this may be part of the disease process.[5] Increased levels of pyroglutamic acid in the blood, or 5-oxoprolinuria, can occur following paracetamol overdose, as well as in certain inborn errors of metabolism, causing an acidosis known as high anion gap metabolic acidosis.[1][6]


The sodium salt of pyroglutamic acid—known either as sodium pyroglutamate, sodium PCA, or sodium pidolate—is used for dry skin and hair products, as it is a humectant. It has low toxicity and is not a skin irritant, but its use in products is limited by a high price.[7][8]

L-pyroglutamic acid is sold online as a nootropic dietary supplement.[9][10]

Magnesium pidolate, the magnesium salt of pyroglutamic acid, is found in some mineral supplements. In a preclinical study, additional pharmacological properties of pyroglutamic acid were revealed such as anti-phosphodiesterase type 5, anti-angiotensin-converting enzyme, and anti-urease activities [11]


  1. ^ a b c d Kumar, Akhilesh; Bachhawat, Anand K. (January 25, 2012). "Pyroglutamic acid: throwing light on a lightly studied metabolite" (PDF). 102 (2): 208. Cite journal requires |journal= (help)
  2. ^ Schilling, S.; Wasternack, C.; Demuth, H.U. (2008), "Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution", Biol. Chem., 389 (8): 983–91, doi:10.1515/BC.2008.111, PMID 18979624.
  3. ^ Podell, David N.; Abraham, George N. (1978), "A technique for the removal of pyroglutamic acid from the amino terminus of proteins using calf liver pyroglutamate amino peptidase", Biochem. Biophys. Res. Commun., 81 (1): 176–85, doi:10.1016/0006-291X(78)91646-7, PMID 26343.
  4. ^ Pepeu, Giancarlo; Spignoli, Giacomo (1989). "Nootropic drugs and brain cholinergic mechanisms". Prog Neuropsychopharmacol Biol Psychiatry. 13 (Supplement 1): S77–88. doi:10.1016/0278-5846(89)90112-7. PMID 2694231.
  5. ^ Jawhar, S; Wirths, O; Bayer, TA (November 11, 2011). "Pyroglutamate amyloid-β (Aβ): a hatchet man in Alzheimer disease". J Biol Chem. 286 (45): 38825–32. doi:10.1074/jbc.R111.288308. PMC 3234707. PMID 21965666.
  6. ^ Liss, DB; Paden, MS; Schwarz, ES; Mullins, ME (November 2013). "What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?". Clin Toxicol. 51 (9): 817–27. doi:10.3109/15563650.2013.844822. PMID 24111553.
  7. ^ "Hydromol® (Alliance)". British National Formulary. Retrieved December 5, 2015.
  8. ^ Jungermann, Eric; Sonntag, Norman O.V (1991-07-19). "Alternatives to Glycerine". In Eric Jungermann, Norman O.V. Sonnta (eds.). Glycerine: A Key Cosmetic Ingredient. p. 424. ISBN 9780824784652.CS1 maint: uses editors parameter (link)
  9. ^ DellaVecchia, Matthew J. (December 2013). "Inaccurate Serelaxin Chemical Structure". Pharmacy and Therapeutics. 38 (12): 763. PMC 3875272. PMID 24391398.
  10. ^ McDougall, Jr., Graham J.; Austin-Wells, Vonnette; Zimmerman, Teena (December 2005). "Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement". J Holist Nurs. 23 (4): 415–433. doi:10.1177/0898010105280097. PMC 2398696. PMID 16251490. (table 1)
  11. ^ Šudomová M, Hassan STS, Khan H, Rasekhian M, Nabavi SM. A Multi-Biochemical and In Silico Study on Anti-Enzymatic Actions of Pyroglutamic Acid against PDE-5, ACE, and Urease Using Various Analytical Techniques: Unexplored Pharmacological Properties and Cytotoxicity Evaluation. Biomolecules. 2019 Aug 21;9(9). pii: E392. doi: 10.3390/biom9090392.