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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/28 19:45:56」(JST)

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Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid, or pyroglutamate for its basic form) is an uncommon and little studied amino acid derivative in which the free amino group of glutamic acid or glutamine cyclizes to form a lactam.^[1] 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. This is one of several forms of blocked N-terminals 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, also known as pidolic 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] It may function to store glutamate, but also acts to oppose the action of glutamate including in the brain.^[1] It also acts on the cholinergic system in the brain,^[3] and Amyloid β containing pyroglutamic acid is increased in Alzheimer's disease and may be involved in the disease process.^[4] Levels of pyroglutamic acid in the blood, called 5-oxoprolinuria, can increase following paracetamol overdose or in inborn error of metabolisms, causing an increased level of acidity called a high anion gap metabolic acidosis.^[1]^[5]

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.^[6]^[7]

L-pyroglutamic acid is sold online as a dietary supplement.^[8]^[9]

Magnesium pidolate, the magnesium salt of pyroglutamic acid, is a mineral supplement.

References

^ ^a ^b ^c ^d Kumar, Akhilesh; Bachhawat, Anand K. (January 25, 2012). "Pyroglutamic acid: throwing light on a lightly studied metabolite" (PDF) 102 (2): 208.
^ 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 .
^ Pepeu, Giancarlo; Spignoli, Giacomo (1989). "Nootropic drugs and brain cholinergic mechanisms". Prog Neuropsychopharmacol Biol Psychiatry 13 (Supplement 1): S77–88.
^ 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.
^ 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 (Phila). 51 (9): 817–27. doi:10.3109/15563650.2013.844822.
^ "Hydromol® (Alliance)". British National Formulary. Retrieved December 5, 2015.
^ Eric Jungermann, Norman O.V. Sonnta (eds.). "Alternatives to Glycerine". Glycerine: A Key Cosmetic Ingredient. p. 424.
^ DellaVecchia, Matthew J. (December 2013). "Inaccurate Serelaxin Chemical Structure". Pharmacy and Therapeutics 38 (12): 763.
^ 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. (table 1)

English Journal

Transient 5-oxoprolinuria: unusually high anion gap acidosis in an infant.

Hulley SL1, Perring J2, Manning N3, Olpin S4, Yap S5.
European journal of pediatrics.Eur J Pediatr.2015 Dec;174(12):1685-8. doi: 10.1007/s00431-015-2585-6. Epub 2015 Jul 1.
Transient 5-oxoprolinuria is a phenomenon that is well recognised in adults. We illustrate an unusual paediatric case of transient 5-oxoprolinuria presenting during an episode of severe sepsis with concomitant paracetamol use. The 15-month-old patient had an extremely high anion gap metabolic acidos
PMID 26122794

An anti-pyroglutamate-3 Aβ vaccine reduces plaques and improves cognition in APPswe/PS1ΔE9 mice.

Frost JL1, Liu B2, Rahfeld JU3, Kleinschmidt M3, O'Nuallain B2, Le KX1, Lues I3, Caldarone BJ4, Schilling S3, Demuth HU3, Lemere CA5.
Neurobiology of aging.Neurobiol Aging.2015 Dec;36(12):3187-99. doi: 10.1016/j.neurobiolaging.2015.08.021. Epub 2015 Aug 31.
Pyroglutamate-3 amyloid-beta (pGlu-3 Aβ) is an N-terminally truncated Aβ isoform likely playing a decisive role in Alzheimer's disease pathogenesis. Here, we describe a prophylactic passive immunization study in APPswe/PS1ΔE9 mice using a novel pGlu-3 Aβ immunoglobulin G1 (IgG1) monoclonal antib
PMID 26453001

Copper binding to naturally occurring, lactam form of angiogenin differs from that to recombinant protein, affecting their activity.

La Mendola D1, Arnesano F2, Hansson Ö3, Giacomelli C1, Calò V2, Mangini V2, Magrì A4, Bellia F4, Trincavelli ML1, Martini C1, Natile G2, Rizzarelli E4.
Metallomics : integrated biometal science.Metallomics.2015 Nov 23. [Epub ahead of print]
Angiogenin is a member of the ribonuclease family and a normal constituent of human plasma. It is one of the most potent angiogenic factors known and is overexpressed in different types of cancers. Copper is also an essential cofactor in angiogenesis and, during this process, it is mobilized from in
PMID 26594037

Japanese Journal

NMR and biophysical elucidation of structural effects on extra N-terminal methionine residue of recombinant amphibian RNases from Rana catesbeiana

Hsu Chun-Hua,Pan Yun-Ru,Liao You-Di [他],WU Shih-Hsiung,CHEN Chinpan
The journal of biochemistry 148(2), 209-215, 2010-08-01
NAID 10027877747

＜Poster＞Pyroglutamate formation at the N-termini of ABri molecules in familial British dementia is not restricted to the central nervous system

Tomidokoro Yasushi,Tamaoka Akira,Holton Janice L. [他],Lashley Tammaryn,Frangione Blas,Revesz Tamas,Rostagno Agueda,Ghiso Jorge
弘前醫學 61(Supplement), S262-S269, 2010-00-00
… Amyloid molecules harboring pyroglutamate （pGlu） residue at the N-termini are considered to beimportant for the development of cerebral amyloidosis such as Alzheimer's disease and thought to be eitherspontaneously generated or being catalyzed by glutaminyl cyclase. …
NAID 110007617538

Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group.

Kajiwara Kazumi,Watanabe Kentaro,Tokiwa Rei,Kurose Tomoko,Ohno Hiroaki,Tsutsumi Hiroko,Hata Yoji,Izumi Kazuki,Kodama Eiichi,Matsuoka Masao,Oishi Shinya,Fujii Nobutaka
Bioorganic & medicinal chemistry 17(23), 7964-7970, 2009-12-01
… Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. …
NAID 120002098852

「ピログルタミン酸」

Pyroglutamic acid
Names
	Preferred IUPAC name 5-Oxoproline
	Systematic IUPAC name 5-Oxopyrrolidine-2-carboxylic acid
	Other names 2-Pyrrolidone-5-carboxylic acid; Pidolic acid; 5-Oxo-proline
Identifiers
CAS Number	98-79-3 (2S) ; 4042-36-8 (2R) ; 149-87-1
3DMet	B01549
Abbreviations	Glp
Beilstein Reference	82134
ChEBI	CHEBI:16010
ChEMBL	ChEMBL284718
ChemSpider	7127 (2S) ; 388752 (2R) ; 485 ; 8710094 (2S)(3,4-3H2)
DrugBank	DB03088
EC Number	205-748-3
Gmelin Reference	1473408
IUPHAR/BPS	4703
Jmol 3D model	Interactive image
KEGG	C02237
MeSH	Pyrrolidonecarboxylic+acid
PubChem	7405 (2S); 439685 (2R); 499; 10534703 (2S)(3,4-3H2)
RTECS number	TW3710000
UNII	SZB83O1W42
	InChI InChI=1S/C5H7NO3/c7-4-2-1-3(6-4)5(8)9/h3H,1-2H2,(H,6,7)(H,8,9) Key: ODHCTXKNWHHXJC-UHFFFAOYSA-N ; 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 ; 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 Key: ODHCTXKNWHHXJC-VKHMYHEASA-N ;
	SMILES O=C(O)[C@H]1NC(=O)CC1 ;
Properties
Chemical formula	C5H7NO3
Molar mass	129.12 g·mol−1
Melting point	184 °C (363 °F; 457 K)
log P	-0.89
Acidity (pKa)	-1.76, 3.48, 12.76
Basicity (pKb)	15.76, 10.52, 1.24
Isoelectric point	0.94
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references

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英: pyroglutamic acid、pyroglutamate
関: ピドロ酸マグネシウム、ピロリドンカルボン酸

概念

グルタミン酸の分子内環化物

wikip jaより

グルタミン酸のカルボキシル基とアミノ基が分子内縮合反応を起こして、ラクタムを形成したアミノ酸
バクテリオロドプシンを含めた様々なタンパク質で見られる。

その他

サプリメントが存在する。効果の真偽については不明。

Lピログルタミン酸　1000mg　120錠 2,256 円

記憶力や思考力、アルコールによる脳内ダメージのサポートに
脳の働きをアクティブにサポートするアミノ酸サプリメント「Lピログルタミン酸　1000mg」。記憶力や思考力アップを目指す方の脳内サポートはもちろん、スッキリした気分を引きだすストレスケアにも支持されています。
Lピログルタミン酸は、PCAとも呼ばれているアミノ酸の一種。私たちの脳や血液の中に多く存在しています。特に、脳の中でさまざまな情報を運んでいるアセチルコリンやGABAと深いかかわりがあるため、集中力や思考力を高める働きに期待がよせられています。また近年は、アルコールによる、記憶や脳のダメージのケアに注目を集めています。
本品は1粒に1000mgのLピログルタミン酸を配合。毎日の脳内サポートにオススメのサプリメントです。