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
Metabolismedit
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, 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.[1][6]
Usesedit
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.[7][8]
^ abcdKumar, Akhilesh; Bachhawat, Anand K. (2012). "Pyroglutamic acid: throwing light on a lightly studied metabolite" (PDF). Current Science. 102 (2): 288–297. JSTOR 24083854.
^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. PMID 18979624. S2CID 24074284.
^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. doi:10.1016/0006-291X(78)91646-7. PMID 26343.
^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. PMID 2694231. S2CID 11309268.
^Jawhar, Sadim; Wirths, Oliver; Bayer, Thomas A. (11 November 2011). "Pyroglutamate Amyloid-β (Aβ): A Hatchet Man in Alzheimer Disease". Journal of Biological Chemistry. 286 (45): 38825–38832. doi:10.1074/jbc.R111.288308. PMC3234707. PMID 21965666.
^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. PMID 24111553. S2CID 43541851.
^"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. CRC Press. p. 424. ISBN978-0-8247-8465-2.
^DellaVecchia, Matthew J. (December 2013). "Inaccurate Serelaxin Chemical Structure". Pharmacy and Therapeutics. 38 (12): 763. PMC3875272. PMID 24391398.
^McDougall, Graham J.; Austin-Wells, Vonnette; Zimmerman, Teena (24 June 2016). "Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement". Journal of Holistic Nursing. 23 (4): 415–433. doi:10.1177/0898010105280097. PMC2398696. PMID 16251490.
^Šudomová, Miroslava; Hassan, Sherif T. S.; Khan, Haroon; Rasekhian, Mahsa; Nabavi, Seyed Mohammad (21 August 2019). "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. 9 (9): 392. doi:10.3390/biom9090392. PMC6770154. PMID 31438631.
December 15, 2023
pyroglutamic, acid, also, known, oxoproline, pidolic, acid, ubiquitous, understudied, natural, amino, acid, derivative, which, free, amino, group, glutamic, acid, glutamine, cyclizes, form, lactam, names, pyroglutamic, acid, conjugate, base, anion, salts, este. 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 1 The names of pyroglutamic acid conjugate base anion salts and esters are pyroglutamate 5 oxoprolinate or pidolate Pyroglutamic acid NamesPreferred IUPAC name 5 OxoprolineSystematic IUPAC name 5 Oxopyrrolidine 2 carboxylic acidOther names 2 Pyrrolidone 5 carboxylic acidPidolic acid5 Oxo prolineIdentifiersCAS Number 149 87 1 R S Y4042 36 8 R Y98 79 3 S Y3D model JSmol Interactive image3DMet B01555Abbreviations GlpBeilstein Reference 82134ChEBI CHEBI 16010 R S NCHEBI 16924 R CHEBI 18183 S ChEMBL ChEMBL284718 NChemSpider 485 R S Y388752 R Y7127 S YDrugBank DB03088 NECHA InfoCard 100 021 578EC Number 205 748 3Gmelin Reference 1473408IUPHAR BPS 4703KEGG C02237 NMeSH Pyrrolidonecarboxylic acidPubChem CID 499 R S 439685 R 7405 S RTECS number TW3710000UNII 6VT1YZM21H R S YSZB83O1W42 S YCompTox Dashboard EPA DTXSID10193432InChI InChI 1S C5H7NO3 c7 4 2 1 3 6 4 5 8 9 h3H 1 2H2 H 6 7 H 8 9 NKey ODHCTXKNWHHXJC UHFFFAOYSA N NInChI 1S C5H7NO3 c7 4 2 1 3 6 4 5 8 9 h3H 1 2H2 H 6 7 H 8 9 t3 m0 s1InChI 1S C5H7NO3 c7 4 2 1 3 6 4 5 8 9 h3H 1 2H2 H 6 7 H 8 9 t3 m0 s1Key ODHCTXKNWHHXJC VKHMYHEASA NSMILES O C O C H 1NC O CC1PropertiesChemical formula C 5H 7N O 3Molar mass 129 115 g mol 1Melting point 184 C 363 F 457 K log P 0 89Acidity pKa 1 76 3 48 12 76Basicity pKb 15 76 10 52 1 24Isoelectric point 0 94Related compoundsRelated compounds proline2 PyrrolidoneExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references 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 lMetabolism editAs 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 g 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 b 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 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 1 6 Uses editThe 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 References edit a b c d Kumar Akhilesh Bachhawat Anand K 2012 Pyroglutamic acid throwing light on a lightly studied metabolite PDF Current Science 102 2 288 297 JSTOR 24083854 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 PMID 18979624 S2CID 24074284 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 doi 10 1016 0006 291X 78 91646 7 PMID 26343 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 PMID 2694231 S2CID 11309268 Jawhar Sadim Wirths Oliver Bayer Thomas A 11 November 2011 Pyroglutamate Amyloid b Ab A Hatchet Man in Alzheimer Disease Journal of Biological Chemistry 286 45 38825 38832 doi 10 1074 jbc R111 288308 PMC 3234707 PMID 21965666 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 PMID 24111553 S2CID 43541851 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 CRC Press p 424 ISBN 978 0 8247 8465 2 DellaVecchia Matthew J December 2013 Inaccurate Serelaxin Chemical Structure Pharmacy and Therapeutics 38 12 763 PMC 3875272 PMID 24391398 McDougall Graham J Austin Wells Vonnette Zimmerman Teena 24 June 2016 Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement Journal of Holistic Nursing 23 4 415 433 doi 10 1177 0898010105280097 PMC 2398696 PMID 16251490 Sudomova Miroslava Hassan Sherif T S Khan Haroon Rasekhian Mahsa Nabavi Seyed Mohammad 21 August 2019 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 9 9 392 doi 10 3390 biom9090392 PMC 6770154 PMID 31438631 Retrieved from https en wikipedia org w index php title Pyroglutamic acid amp oldid 1175822821, wikipedia, wiki, book, books, library,
