Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but understudied natural amino acid derivative in which the free amino group of glutamic acid or glutaminecyclizes 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
Metabolism
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]
The sodiumsalt 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.[9][10]
↑ Schilling, Stephan; Wasternack, Claus; Demuth, Hans-Ulrich (1 August 2008). "Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution". Biological Chemistry. 389 (8): 983–91. doi:10.1515/BC.2008.111. PMID18979624. S2CID24074284.
↑ Podell, David N.; Abraham, George N. (March 1978). "A technique for the removal of pyroglutamic acid from the amino terminus of proteins using calf liver pyroglutamate amino peptidase". Biochemical and Biophysical Research Communications. 81 (1): 176–185. Bibcode:1978BBRC...81..176P. doi:10.1016/0006-291X(78)91646-7. PMID26343.
↑ Pepeu, Giancarlo; Spignoli, Giacomo (January 1989). "Nootropic drugs and brain cholinergic mechanisms". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 13: S77 –S88. doi:10.1016/0278-5846(89)90112-7. PMID2694231. S2CID11309268.
↑ Liss, D. B.; Paden, M. S.; Schwarz, E. S.; Mullins, M. E. (11 October 2013). "What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?". Clinical Toxicology. 51 (9): 817–827. doi:10.3109/15563650.2013.844822. PMID24111553. S2CID43541851.
↑ 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. CRC Press. p.424. ISBN978-0-8247-8465-2.
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