Pyroglutamic acid

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Pyroglutamic acid
Stereo structural formula of (2S)-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
98-79-3 (2S) YesY
4042-36-8 (2R) YesY
149-87-1 YesY
3DMet B01549
Abbreviations Glp
82134
ChEBI CHEBI:16010 N
ChEMBL ChEMBL284718 N
ChemSpider 7127 (2S) YesY
388752 (2R) YesY
485 YesY
8710094 (2S)(3,4-3H2) YesY
DrugBank DB03088 N
EC Number 205-748-3
1473408
4703
Jmol 3D model Interactive image
KEGG C02237 N
MeSH Pyrrolidonecarboxylic+acid
PubChem 7405 (2S)
439685 (2R)
499
10534703 (2S)(3,4-3H2)
RTECS number TW3710000
UNII SZB83O1W42 YesY
Properties
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).
N verify (what is YesYN ?)
Infobox references

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[edit]

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[edit]

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[edit]

  1. ^ 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. 
  2. ^ 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 .
  3. ^ Pepeu, Giancarlo; Spignoli, Giacomo (1989). "Nootropic drugs and brain cholinergic mechanisms". Prog Neuropsychopharmacol Biol Psychiatry 13 (Supplement 1): S77–88. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ "Hydromol® (Alliance)". British National Formulary. Retrieved December 5, 2015. 
  7. ^ Eric Jungermann, Norman O.V. Sonnta (eds.). "Alternatives to Glycerine". Glycerine: A Key Cosmetic Ingredient. p. 424. 
  8. ^ DellaVecchia, Matthew J. (December 2013). "Inaccurate Serelaxin Chemical Structure". Pharmacy and Therapeutics 38 (12): 763. PMC 3875272. 
  9. ^ 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. PMC 2398696.  (table 1)