Chemistry:Pyroglutamic acid

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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

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] 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]

Uses

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.

References

  1. 1.0 1.1 1.2 1.3 Kumar, Akhilesh; Bachhawat, Anand K. (January 25, 2012). Pyroglutamic acid: throwing light on a lightly studied metabolite. 102. p. 208. http://www.currentscience.ac.in/Volumes/102/02/0288.pdf. 
  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. 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. https://www.evidence.nhs.uk/formulary/bnf/current/13-skin/132-emollient-and-barrier-preparations/1321-emollients/proprietary-emollient-preparations/hydromol. Retrieved December 5, 2015. 
  8. Jungermann, Eric; Sonntag, Norman O.V (1991-07-19). "Alternatives to Glycerine". in Eric Jungermann, Norman O.V. Sonnta. Glycerine: A Key Cosmetic Ingredient. p. 424. ISBN 9780824784652. https://books.google.co.uk/books?id=kGTsPEMNLt0C&pg=RA1-PA424. 
  9. DellaVecchia, Matthew J. (December 2013). "Inaccurate Serelaxin Chemical Structure". Pharmacy and Therapeutics 38 (12): 763. 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. PMID 16251490.  (table 1)

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