Pyroglutamic acid explained

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 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.[1] 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.[2]

Pyroglutamic acid exists as two distinct enantiomers:

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. 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;[3] Amyloid β containing pyroglutamic acid is increased in Alzheimer's disease; this may be part of the disease process.[4] Increased levels of pyroglutamic acid in the blood, leading to excess in the urine (5-oxoprolinuria), can occur following paracetamol overdose, as well as in certain inborn errors of metabolism, causing high anion gap metabolic acidosis.[5] [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.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]

Notes and References

  1. Schilling . Stephan . Wasternack . Claus . Demuth . Hans-Ulrich . Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution . Biological Chemistry . 1 August 2008 . 389 . 8 . 983–91 . 10.1515/BC.2008.111 . 18979624 . 24074284.
  2. Podell . David N. . Abraham . George N. . 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 . March 1978 . 81 . 1 . 176–185 . 10.1016/0006-291X(78)91646-7 . 26343.
  3. Pepeu . Giancarlo . Spignoli . Giacomo . Nootropic drugs and brain cholinergic mechanisms . Progress in Neuro-Psychopharmacology and Biological Psychiatry . January 1989 . 13 . S77–S88 . 10.1016/0278-5846(89)90112-7 . 2694231 . 11309268 .
  4. Jawhar . Sadim . Wirths . Oliver . Bayer . Thomas A. . Pyroglutamate Amyloid-β (Aβ): A Hatchet Man in Alzheimer Disease . Journal of Biological Chemistry . 11 November 2011 . 286 . 45 . 38825–38832 . 10.1074/jbc.R111.288308 . 21965666 . 3234707 . free.
  5. Kumar . Akhilesh . Bachhawat . Anand K. . Pyroglutamic acid: throwing light on a lightly studied metabolite . Current Science . 2012 . 102 . 2 . 288–297 . 24083854 .
  6. Liss . D. B. . Paden . M. S. . Schwarz . E. S. . Mullins . M. E. . What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure? . Clinical Toxicology . 11 October 2013 . 51 . 9 . 817–827 . 10.3109/15563650.2013.844822 . 24111553 . 43541851.
  7. Web site: Hydromol® (Alliance). British National Formulary. December 5, 2015.
  8. Book: https://books.google.com/books?id=kGTsPEMNLt0C&pg=RA1-PA424. Glycerine: A Key Cosmetic Ingredient. Alternatives to Glycerine. Eric Jungermann . Norman O.V. Sonnta. 424. 978-0-8247-8465-2. Jungermann. Eric. Sonntag. Norman O.V. 1991-07-19. CRC Press .
  9. DellaVecchia . Matthew J. . Inaccurate Serelaxin Chemical Structure . Pharmacy and Therapeutics . December 2013 . 38 . 12 . 763 . 24391398 . 3875272 .
  10. McDougall . Graham J. . Austin-Wells . Vonnette . Zimmerman . Teena . Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement . Journal of Holistic Nursing . 24 June 2016 . 23 . 4 . 415–433 . 10.1177/0898010105280097 . 16251490 . 2398696 .
  11. Šudomová . Miroslava . Hassan . Sherif T. S. . Khan . Haroon . Rasekhian . Mahsa . Nabavi . Seyed Mohammad . 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 . 21 August 2019 . 9 . 9 . 392 . 10.3390/biom9090392 . 31438631 . 6770154 . free.

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