urocanic acid
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 436802684
| ImageFile =Urocanic acid.svg
| ImageSize =
| PIN = (2E)-3-(1H-imidazol-4-yl)prop-2-enoic acid
| OtherNames = (E)-3-(1H-imidazol-4-yl)acrylic acid
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo =104-98-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = G8D26XJJ3B
| PubChem =1178
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 30817
| MeSHName =Urocanic+acid
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 643824
| SMILES = c1c(nc[nH]1)/C=C/C(=O)O
| InChI = 1/C6H6N2O2/c9-6(10)2-1-5-3-7-4-8-5/h1-4H,(H,7,8)(H,9,10)/b2-1+
| InChIKey = LOIYMIARKYCTBW-OWOJBTEDBA
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C6H6N2O2/c9-6(10)2-1-5-3-7-4-8-5/h1-4H,(H,7,8)(H,9,10)/b2-1+
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = LOIYMIARKYCTBW-OWOJBTEDSA-N
}}
|Section2={{Chembox Properties
| Formula =C6H6N2O2
| MolarMass =138.124 g/mol
| Appearance =
| Density =
| MeltingPtC = 225
| BoilingPt =
| Solubility =
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|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
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Urocanic acid (formally trans-Urocanic acid) is an intermediate in the catabolism of L-histidine. The cis-urocanic acid isomer is rare.
Metabolism
It is formed from L-histidine through the action of histidine ammonialyase (also known as histidase or histidinase) by elimination of ammonium.
In the liver, urocanic acid is transformed by urocanate hydratase (or urocanase) to 4-imidazolone-5-propionic acid and subsequently to glutamic acid.
Clinical significance
Inherited deficiency of urocanase leads to elevated levels of urocanic acid in the urine, a condition known as urocanic aciduria.
An important role for the onset of atopic dermatitis and asthma has been attributed to filaggrin, a skin precursor of urocanic acid.{{cite journal | vauthors = Park KD, Pak SC, Park KK | title = The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis | journal = Toxins | volume = 9 | issue = 1 | pages = 3 | date = December 2016 | pmid = 28025545 | pmc = 5299398 | doi = 10.3390/toxins9010003 | doi-access = free }}{{cite journal | vauthors = Irvine AD, McLean WH, Leung DY | title = Filaggrin mutations associated with skin and allergic diseases | journal = The New England Journal of Medicine | volume = 365 | issue = 14 | pages = 1315–27 | date = October 2011 | pmid = 21991953 | doi = 10.1056/nejmra1011040 }}
Urocanic acid is thought to be a significant attractant of the nematode parasite Strongyloides stercoralis,{{Cite journal|doi=10.1073/pnas.0610193104|title=Urocanic acid is a major chemoattractant for the skin-penetrating parasitic nematode Strongyloides stercoralis|year=2007|last1=Safer|first1=D.|last2=Brenes|first2=M.|last3=Dunipace|first3=S.|last4=Schad|first4=G.|journal=Proceedings of the National Academy of Sciences|volume=104|issue=5|pages=1627–1630|pmid=17234810|pmc=1785286|doi-access=free}} in part because of relatively high levels in the plantar surfaces of the feet, the site through which this parasite often enters the body.
Function
Urocanic acid is found in animal sweat and skin. its concentration varies greatly between people, from 4 nM per cm2 to 34 nM per cm2 with only small differences between areas other than at the sole of the foot and between sun-exposed and unexposed areas.{{Cite journal |last=Kavanagh |first=G. |last2=Crosby |first2=J. |last3=Norval |first3=M. |date=2006-07-29 |title=Urocanic acid isomers in human skin: analysis of site variation |url=https://academic.oup.com/bjd/article/133/5/728/6681493 |journal=British Journal of Dermatology |language=en |volume=133 |issue=5 |pages=728–731 |doi=10.1111/j.1365-2133.1995.tb02746.x}} Concentration does not link with age, sex, skin tone, photosensitivity, and stratum corneum thickness.{{Cite journal |last=DE Fine Olivarius |last2=Wulf |last3=Crosby |last4=Norval |date=1998 |title=Urocanic acid isomers and photosensitivity in healthy children: UROCANIC ACID AND PHOTOSENSITIVITY IN CHILDHOOD |url=https://academic.oup.com/bjd/article/139/4/605/6683728 |journal=British Journal of Dermatology |language=en |volume=139 |issue=4 |pages=605–609 |doi=10.1046/j.1365-2133.1998.02455.x}}
Among other functions, urocanic acid acts as an endogenous sunscreen or photoprotectant against UVB-induced DNA damage.{{Cite journal |last=Fan |first=Jiayun |last2=Wooley |first2=Jack M. |last3=Sanders |first3=Hans |last4=Stavros |first4=Vasilios G. |last5=Buma |first5=Wybren Jan |date=2024 |title=Urocanic acid as a novel scaffold for next-gen nature-inspired sunscreens: II. Time-resolved spectroscopy under solution conditions |url=https://xlink.rsc.org/?DOI=D4CP02088J |journal=Physical Chemistry Chemical Physics |language=en |volume=26 |issue=43 |pages=27281–27291 |doi=10.1039/D4CP02088J |issn=1463-9076|doi-access=free }} However, some studies have questioned this.
Urocanic acid is found predominantly in the stratum corneum of the skin and it is likely that most of it is derived from filaggrin catabolism (a histidine-rich protein). When exposed to UVB irradiation, trans-urocanic acid is converted in vitro and in vivo to cis-urocanic acid (cis-UCA).{{cite journal | vauthors = Egawa M, Nomura J, Iwaki H | title = The evaluation of the amount of cis- and trans-urocanic acid in the stratum corneum by Raman spectroscopy | journal = Photochemical and Photobiological Sciences | volume = 9 | issue = 5 | pages = 730–3 | date = May 2010 | pmid = 20442934 | doi = 10.1039/b9pp00143c | doi-access = free }} The cis form is known to activate regulatory T cells.{{cite journal | vauthors = Schwarz T | title = Mechanisms of UV-induced immunosuppression | journal = The Keio Journal of Medicine | volume = 54 | issue = 4 | pages = 165–71 | date = December 2005 | pmid = 16452825 | doi = 10.2302/kjm.54.165| url = http://www.kjm.keio.ac.jp/past/54/4/165.pdf | doi-access = free }} Measuring cis-UCA provides a sensitive means at sub-erythemal doses to detect UVB, and so offers a potential method to assess the UVR protection provided by suncreams.{{Cite journal |last=Keurentjes |first=Anne Josephine |last2=Jakasa |first2=Ivone |last3=van Dijk |first3=Arjan |last4=van Putten |first4=Edith |last5=Brans |first5=Richard |last6=John |first6=Swen Malte |last7=Rustemeyer |first7=Thomas |last8=van der Molen |first8=Henk F. |last9=Kezic |first9=Sanja |date=2022 |title=Stratum corneum biomarkers after in vivo repeated exposure to sub‐erythemal dosages of ultraviolet radiation in unprotected and sunscreen (SPF 50+) protected skin |url=https://onlinelibrary.wiley.com/doi/10.1111/phpp.12717 |journal=Photodermatology, Photoimmunology & Photomedicine |language=en |volume=38 |issue=1 |pages=60–68 |doi=10.1111/phpp.12717 |issn=0905-4383}}
Some studies attribute filaggrin an important role in keeping the skin surface slightly acidic, through a breaking down mechanism to form histidine and subsequently trans-urocanic acid,{{cite journal | vauthors = Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L, Høgh JK, Hellgren LI, Jemec GB, Agner T, Weidinger S | title = Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema | journal = Allergy | volume = 65 | issue = 7 | pages = 911–8 | date = July 2010 | pmid = 20132155 | doi = 10.1111/j.1398-9995.2010.02326.x | s2cid = 24679127 }} however others have shown that the filaggrin–histidine–urocanic acid cascade is not essential for skin acidification.{{cite journal | vauthors = Fluhr JW, Elias PM, Man MQ, Hupe M, Selden C, Sundberg JP, Tschachler E, Eckhart L, Mauro TM, Feingold KR | title = Is the filaggrin-histidine-urocanic acid pathway essential for stratum corneum acidification? | journal = The Journal of Investigative Dermatology | volume = 130 | issue = 8 | pages = 2141–4 | date = August 2010 | pmid = 20376063 | pmc = 4548931 | doi = 10.1038/jid.2010.74 }}
History
Urocanic acid was first isolated in 1874 by the chemist Max Jaffé from the urine of a dog,{{cite journal | vauthors = Jaffe M | doi = 10.1002/cber.187500801267 | title = Ueber die Urocaninsäure | trans-title = About urocanic acid | language = German | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 8 | issue = 1 | date = 1875 | pages = 811–813 | url = https://zenodo.org/record/1425082 }}{{cite journal | vauthors = Jaffe M | doi = 10.1002/cber.187400702225 | title = Ueber einen neuen Bestandtheil des Hundeharns | trans-title = Concerning a new constituent in the urine of dogs | language = German | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 7 | issue = 2 | date = 1874 | pages = 1669–1673 | url = https://zenodo.org/record/1425064 }} hence the name ({{langx|la|urina}} = urine, and canis = dog).
See also
References
{{reflist|32em}}
External links
- [https://web.archive.org/web/20070808184119/http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=80 The Online Metabolic and Molecular Bases of Inherited Disease - Chapter 80] - An overview of disorders of histidine metabolism, including urocanic aciduria.
{{Amino acid metabolism intermediates}}