Editing Pyroglutamic acid

{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 464377606
| ImageFile = Pyroglutamic acid.svg
| ImageSize = 140px
| PIN = 5-Oxoproline
| SystematicName = 5-Oxopyrrolidine-2-carboxylic acid
| OtherNames = {{ubl|2-Pyrrolidone-5-carboxylic acid| Pidolic acid |5-Oxo-proline}}
| Section1 = {{Chembox Identifiers
| IUPHAR_ligand = 4703
| Abbreviations = Glp
| InChI = 1S/C5H7NO3/c7-4-2-1-3(6-4)5(8)9/h3H,1-2H2,(H,6,7)(H,8,9)/t3-/m0/s1
| InChIKey1 = ODHCTXKNWHHXJC-VKHMYHEASA-N
| InChI1 = 1S/C5H7NO3/c7-4-2-1-3(6-4)5(8)9/h3H,1-2H2,(H,6,7)(H,8,9)/t3-/m0/s1
| CASNo = 149-87-1
| CASNo_Comment = (''R/S'')
| CASNo_Ref = {{cascite|correct|??}}
| CASNo1_Ref = {{cascite|correct|??}}
| CASNo1 = 4042-36-8
| CASNo1_Comment = (''R'')
| CASNo2_Ref = {{cascite|correct|CAS}}
| CASNo2 = 98-79-3
| CASNo2_Comment = (''S'')
| PubChem = 499
| PubChem_Comment = (''R/S'')
| PubChem1 = 439685
| PubChem1_Comment = (''R'')
| PubChem2 = 7405
| PubChem2_Comment = (''S'')
| ChemSpiderID2 = 7127
| ChemSpiderID2_Comment = (''S'')
| ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID1 = 388752
| ChemSpiderID1_Comment = (''R'')
| ChemSpiderID1_Ref = {{chemspidercite|correct|ChemSpider}}
| ChemSpiderID = 485
| ChemSpiderID_Ref = {{chemspidercite|correct|ChemSpider}}
| ChemSpiderID_Comment = (''R/S'')
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = SZB83O1W42
| UNII2_Comment = (''S'')
| UNII = 6VT1YZM21H
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Comment = (''R/S'')
| EINECS = 205-748-3
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB03088
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C02237
| MeSHName = Pyrrolidonecarboxylic+acid
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 16010
| ChEBI_Comment = (''R/S'')
| ChEBI1 = 16924
| ChEBI1_Comment = (''R'')
| ChEBI2 = 18183
| ChEBI2_Comment = (''S'')
| RTECS = TW3710000
| SMILES = O=C(O)[C@H]1NC(=O)CC1
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 284718
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C5H7NO3/c7-4-2-1-3(6-4)5(8)9/h3H,1-2H2,(H,6,7)(H,8,9)
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = ODHCTXKNWHHXJC-UHFFFAOYSA-N
| Gmelin = 1473408
| Beilstein = 82134
| 3DMet = B01555
}}
| Section2 = {{Chembox Properties
| C=5 | H=7 | N=1 | O=3  
| MeltingPtC = 184
| LogP = −0.89
| pKa = −1.76, 3.48, 12.76
| pKb = 15.76, 10.52, 1.24
| IsoelectricPt = 0.94}}
|Section9={{Chembox Related
| OtherCompounds = [[proline]]<br/>[[2-Pyrrolidone]]}}
}}

'''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]] [[condensation reaction|cyclizes]] to form a [[lactam]].<ref name=throwing/> The names of pyroglutamic acid [[conjugate base]], [[anion]], [[salt (chemistry)|salt]]s, and [[ester]]s are '''pyroglutamate''', 5-oxoprolinate, or pidolate.
[[File:Formation_of_5-oxoproline_from_N-terminal_Gln.svg|thumb|left|250px|Formation of pyroglutamic acid from ''N''-terminal glutamine.]]
It is a metabolite in the glutathione cycle that is converted to glutamate by [[5-oxoprolinase (ATP-hydrolysing)|5-oxoprolinase]].  Pyroglutamate is found in many proteins including [[bacteriorhodopsin]]. [[N-terminus|''N''-terminal]] glutamic acid and glutamine residues can spontaneously cyclize to become pyroglutamate, or enzymatically converted by [[Glutaminyl-peptide cyclotransferase|glutaminyl cyclases]].<ref>{{cite journal |last1=Schilling |first1=Stephan |last2=Wasternack |first2=Claus |last3=Demuth |first3=Hans-Ulrich |title=Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution |journal=Biological Chemistry |date=1 August 2008 |volume=389 |issue=8 |pages=983–91 |doi=10.1515/BC.2008.111 |pmid=18979624 |s2cid=24074284}}</ref> This is one of several forms of blocked ''N''-termini which present a problem for ''N''-terminal sequencing using [[Edman degradation|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.<ref>{{cite journal |last1=Podell |first1=David N. |last2=Abraham |first2=George N. |title=A technique for the removal of pyroglutamic acid from the amino terminus of proteins using calf liver pyroglutamate amino peptidase |journal=Biochemical and Biophysical Research Communications |date=March 1978 |volume=81 |issue=1 |pages=176–185 |doi=10.1016/0006-291X(78)91646-7 |pmid=26343}}</ref>

Pyroglutamic acid exists as two distinct [[enantiomers]]:
*(2''R'') or <small>D</small> which happens to be (+) or ''d'' 
*(2''S'') or <small>L</small> which happens to be (–) or ''l''

==Metabolism==
As first discovered in 1882, pyroglutamic acid can be formed by heating glutamic acid at 180&nbsp;°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]].<ref name=throwing/> Pyroglutamic acid may function in glutamate storage, and acts to oppose the action of glutamate, including in the brain.<ref name=throwing/> It also acts on the brain's [[cholinergic system]];<ref>{{cite journal |last1=Pepeu |first1=Giancarlo |last2=Spignoli |first2=Giacomo |title=Nootropic drugs and brain cholinergic mechanisms |journal=Progress in Neuro-Psychopharmacology and Biological Psychiatry |date=January 1989 |volume=13 |pages=S77–S88 |doi=10.1016/0278-5846(89)90112-7 |pmid=2694231 |s2cid=11309268 }}</ref> [[Amyloid β]] containing pyroglutamic acid is increased in [[Alzheimer's disease]]; this may be part of the disease process.<ref>{{cite journal |last1=Jawhar |first1=Sadim |last2=Wirths |first2=Oliver |last3=Bayer |first3=Thomas A. |title=Pyroglutamate Amyloid-β (Aβ): A Hatchet Man in Alzheimer Disease |journal=Journal of Biological Chemistry |date=11 November 2011 |volume=286 |issue=45 |pages=38825–38832 |doi=10.1074/jbc.R111.288308 |pmid=21965666 |pmc=3234707 |doi-access=free}}</ref>
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 [[Glutathione synthetase deficiency|inborn errors of metabolism]], causing [[high anion gap metabolic acidosis]].<ref name=throwing>{{cite journal |last1=Kumar |first1=Akhilesh |last2=Bachhawat |first2=Anand K. |title=Pyroglutamic acid: throwing light on a lightly studied metabolite |journal=Current Science |date=2012 |volume=102 |issue=2 |pages=288–297 |jstor=24083854 |url=http://www.currentscience.ac.in/Volumes/102/02/0288.pdf}}</ref><ref>{{cite journal |last1=Liss |first1=D. B. |last2=Paden |first2=M. S. |last3=Schwarz |first3=E. S. |last4=Mullins |first4=M. E. |title=What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure? |journal=Clinical Toxicology |date=11 October 2013 |volume=51 |issue=9 |pages=817–827 |doi=10.3109/15563650.2013.844822 |pmid=24111553 |s2cid=43541851}}</ref>

==Uses==
The [[sodium]] [[salt (chemistry)|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.<ref>{{cite web|url=https://www.evidence.nhs.uk/formulary/bnf/current/13-skin/132-emollient-and-barrier-preparations/1321-emollients/proprietary-emollient-preparations/hydromol|title=Hydromol® (Alliance)|work=British National Formulary|access-date=December 5, 2015}}</ref><ref>{{cite book|chapter-url=https://books.google.com/books?id=kGTsPEMNLt0C&pg=RA1-PA424|title=Glycerine: A Key Cosmetic Ingredient|chapter=Alternatives to Glycerine|editor1=Eric Jungermann |editor2=Norman O.V. Sonnta|page=424|isbn=978-0-8247-8465-2|last1=Jungermann|first1=Eric|last2=Sonntag|first2=Norman O.V|date=1991-07-19|publisher=CRC Press }}</ref>

<small>L</small>-pyroglutamic acid is sold online as a [[nootropic]] [[dietary supplement]].<ref>{{cite journal |last1=DellaVecchia |first1=Matthew J. |title=Inaccurate Serelaxin Chemical Structure |journal=Pharmacy and Therapeutics |date=December 2013 |volume=38 |issue=12 |pages=763 |pmid=24391398 |pmc=3875272 }}</ref><ref>{{cite journal |last1=McDougall |first1=Graham J. |last2=Austin-Wells |first2=Vonnette |last3=Zimmerman |first3=Teena |title=Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement |journal=Journal of Holistic Nursing |date=24 June 2016 |volume=23 |issue=4 |pages=415–433 |doi=10.1177/0898010105280097 |pmid=16251490 |pmc=2398696 }}</ref>

[[Magnesium pidolate]], the magnesium salt of pyroglutamic acid, is found in some [[mineral supplement]]s.
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.<ref>{{cite journal |last1=Šudomová |first1=Miroslava |last2=Hassan |first2=Sherif T. S. |last3=Khan |first3=Haroon |last4=Rasekhian |first4=Mahsa |last5=Nabavi |first5=Seyed Mohammad |title=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 |journal=Biomolecules |date=21 August 2019 |volume=9 |issue=9 |pages=392 |doi=10.3390/biom9090392 |pmid=31438631 |pmc=6770154 |doi-access=free}}</ref>

==References==
{{reflist}}

{{Protein primary structure}}

[[Category:Pyrrolidones]]
[[Category:Alpha-Amino acids]]
[[Category:Glutamates]]
[[Category:Non-proteinogenic amino acids]]
[[Category:Cyclic amino acids]]
[[Category:Secondary amino acids]]