|Preferred IUPAC name
|Systematic IUPAC name
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||129.115 g·mol−1|
|Melting point||184 °C (363 °F; 457 K)|
|Acidity (pKa)||-1.76, 3.48, 12.76|
|Basicity (pKb)||15.76, 10.52, 1.24|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
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. The names of pyroglutamic acid conjugate base, anion, salts, and esters are pyroglutamate, 5-oxoprolinate, or pidolate.
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. 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.
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. Pyroglutamic acid may function in glutamate storage, and acts to oppose the action of glutamate, including in the brain. It also acts on the brain's cholinergic system; Amyloid β containing pyroglutamic acid is increased in Alzheimer's disease; this may be part of the disease process. 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.
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.
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 
- Kumar, Akhilesh; Bachhawat, Anand K. (January 25, 2012). "Pyroglutamic acid: throwing light on a lightly studied metabolite" (PDF). 102 (2): 208. Cite journal requires
- 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.
- 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.
- 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.
- 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.
- 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.
- "Hydromol® (Alliance)". British National Formulary. Retrieved December 5, 2015.
- 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)
- DellaVecchia, Matthew J. (December 2013). "Inaccurate Serelaxin Chemical Structure". Pharmacy and Therapeutics. 38 (12): 763. PMC 3875272. PMID 24391398.
- 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)
- 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.