Urocanic acid

Last updated
Urocanic acid
Urocanic acid.svg
Names
Preferred IUPAC name
(2E)-3-(1H-imidazol-4-yl)prop-2-enoic acid
Other names
(E)-3-(1H-imidazol-4-yl)acrylic acid
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.002.963 OOjs UI icon edit-ltr-progressive.svg
MeSH Urocanic+acid
PubChem CID
UNII
  • InChI=1S/C6H6N2O2/c9-6(10)2-1-5-3-7-4-8-5/h1-4H,(H,7,8)(H,9,10)/b2-1+ X mark.svgN
    Key: LOIYMIARKYCTBW-OWOJBTEDSA-N X mark.svgN
  • InChI=1/C6H6N2O2/c9-6(10)2-1-5-3-7-4-8-5/h1-4H,(H,7,8)(H,9,10)/b2-1+
    Key: LOIYMIARKYCTBW-OWOJBTEDBA
  • c1c(nc[nH]1)/C=C/C(=O)O
Properties
C6H6N2O2
Molar mass 138.124 g/mol
Melting point 225 °C (437 °F; 498 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Urocanic acid is an intermediate in the catabolism of L-histidine.

Contents

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. [1] [2]

Urocanic acid is thought to be a significant attractant of the nematode parasite Strongyloides stercoralis , [3] 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 was detected in animal sweat and skin where, among other possible functions, it acts as an endogenous sunscreen or photoprotectant against UVB-induced DNA damage. 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 the cis isomer. [4] The cis form is known to activate regulatory T cells. [5]

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, [6] however others have shown that the filaggrin–histidine–urocanic acid cascade is not essential for skin acidification. [7]

History

Urocanic acid was first isolated in 1874 by the chemist Max Jaffé from the urine of a dog, [8] [9] hence the name (Latin : urina = urine, and canis = dog).

See also

Related Research Articles

<span class="mw-page-title-main">Dandruff</span> Skin condition of the scalp

Dandruff is a skin condition that mainly affects the scalp. Symptoms include flaking and sometimes mild itchiness. It can result in social or self-esteem problems. A more severe form of the condition, which includes inflammation of the skin, is known as seborrhoeic dermatitis.

<span class="mw-page-title-main">Irritant diaper dermatitis</span> Medical condition

Irritant diaper dermatitis is a generic term applied to skin rash in the diaper area that are caused by various skin disorders and/or irritants.

Furfural is an organic compound with the formula C4H3OCHO. It is a colorless liquid, although commercial samples are often brown. It has an aldehyde group attached to the 2-position of furan. It is a product of the dehydration of sugars, as occurs in a variety of agricultural byproducts, including corncobs, oat, wheat bran, and sawdust. The name furfural comes from the Latin word furfur, meaning bran, referring to its usual source. Furfural is only derived from lignocellulosic biomass, i.e., its origin is non-food or non-coal/oil based. In addition to ethanol, acetic acid, and sugar, furfural is one of the oldest organic chemicals available readily purified from natural precursors.

<span class="mw-page-title-main">Stratum corneum</span> Outermost layer of the epidermis

The stratum corneum is the outermost layer of the epidermis. The human stratum corneum comprises several levels of flattened corneocytes that are divided into two layers: the stratum disjunctum and stratum compactum. The skin's protective acid mantle and lipid barrier sit on top of the stratum disjunctum. The stratum disjunctum is the uppermost and loosest layer of skin. The stratum compactum is the comparatively deeper, more compacted and more cohesive part of the stratum corneum. The corneocytes of the stratum disjunctum are larger, more rigid and more hydrophobic than that of the stratum compactum.

The Bischler–Möhlau indole synthesis, also often referred to as the Bischler indole synthesis, is a chemical reaction that forms a 2-aryl-indole from an α-bromo-acetophenone and excess aniline; it is named after August Bischler and Richard Möhlau .

<span class="mw-page-title-main">Atopic dermatitis</span> Long-term form of skin inflammation

Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which can thicken over time. AD may also simply be called eczema, a term that generally refers to a larger group of skin conditions.

<span class="mw-page-title-main">Mandelic acid</span> Chemical compound

Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. The racemic mixture is known as paramandelic acid.

<span class="mw-page-title-main">Filaggrin</span>

Filaggrin is a filament-associated protein that binds to keratin fibers in epithelial cells. Ten to twelve filaggrin units are post-translationally hydrolyzed from a large profilaggrin precursor protein during terminal differentiation of epidermal cells. In humans, profilaggrin is encoded by the FLG gene, which is part of the S100 fused-type protein (SFTP) family within the epidermal differentiation complex on chromosome 1q21.

<span class="mw-page-title-main">Hans von Pechmann</span> German chemist

Hans von Pechmann was a German chemist, renowned for his discovery of diazomethane in 1894. Pechmann condensation and Pechmann pyrazole synthesis. He also first prepared 1,2-diketones, acetonedicarboxylic acid, methylglyoxal and diphenyltriketone; established the symmetrical structure of anthraquinone.

<span class="mw-page-title-main">Fischer glycosidation</span>

Fischer glycosidation refers to the formation of a glycoside by the reaction of an aldose or ketose with an alcohol in the presence of an acid catalyst. The reaction is named after the German chemist, Emil Fischer, winner of the Nobel Prize in chemistry, 1902, who developed this method between 1893 and 1895.

Chlorobutanol (trichloro-2-methyl-2-propanol) is a preservative, sedative, hypnotic and weak local anesthetic similar in nature to chloral hydrate. It has antibacterial and antifungal properties. Chlorobutanol is typically used at a concentration of 0.5% where it lends long term stability to multi-ingredient formulations. However, it retains antimicrobial activity at 0.05% in water. Chlorobutanol has been used in anesthesia and euthanasia of invertebrates and fishes. It is a white, volatile solid with a camphor-like odor.

<span class="mw-page-title-main">Histidine ammonia-lyase</span>

Histidine ammonia-lyase is an enzyme that in humans is encoded by the HAL gene. It converts histidine into ammonia and urocanic acid. Its systematic name is L-histidine ammonia-lyase (urocanate-forming).

<span class="mw-page-title-main">Urocanase</span>

Urocanase is the enzyme that catalyzes the second step in the degradation of histidine, the hydration of urocanate into imidazolonepropionate.

Corneocytes are terminally differentiated keratinocytes and compose most of the stratum corneum, the outermost layer of the epidermis. They are regularly replaced through desquamation and renewal from lower epidermal layers and are essential for its function as a skin barrier.

Keratohyalin is a protein structure found in cytoplasmic granules of the keratinocytes in the stratum granulosum of the epidermis. Keratohyalin granules (KHG) mainly consist of keratin, profilaggrin, loricrin and trichohyalin proteins which contribute to cornification or keratinization, the process of the formation of epidermal cornified cell envelope. During the keratinocyte differentiation, these granules maturate and expand in size, which leads to the conversion of keratin tonofilaments into a homogenous keratin matrix, an important step in cornification.

<span class="mw-page-title-main">Oskar Piloty</span> German chemist (1866–1915)

Oskar Piloty was a German chemist.

<span class="mw-page-title-main">Urocanic aciduria</span> Medical condition

Urocanic aciduria is an autosomal recessive metabolic disorder caused by a deficiency of the enzyme urocanase. It is a secondary disorder of histidine metabolism.

<span class="mw-page-title-main">Conhydrine</span> Chemical compound

Conhydrine is a poisonous alkaloid found in poison hemlock in small quantities.

Skin sloughing is the process of shedding dead surface cells from the skin. It is most associated with cosmetic skin maintenance via exfoliation, but can also occur biologically or for medical reasons.

Alexander Ellinger was a German chemist and pharmacologist.

References

  1. Park KD, Pak SC, Park KK (December 2016). "The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis". Toxins. 9 (1): 3. doi: 10.3390/toxins9010003 . PMC   5299398 . PMID   28025545.
  2. Irvine AD, McLean WH, Leung DY (October 2011). "Filaggrin mutations associated with skin and allergic diseases". The New England Journal of Medicine. 365 (14): 1315–27. doi:10.1056/nejmra1011040. PMID   21991953.
  3. Safer, D.; Brenes, M.; Dunipace, S.; Schad, G. (2007). "Urocanic acid is a major chemoattractant for the skin-penetrating parasitic nematode Strongyloides stercoralis". Proceedings of the National Academy of Sciences. 104 (5): 1627–1630. doi: 10.1073/pnas.0610193104 . PMC   1785286 . PMID   17234810.
  4. Egawa M, Nomura J, Iwaki H (May 2010). "The evaluation of the amount of cis- and trans-urocanic acid in the stratum corneum by Raman spectroscopy". Photochemical and Photobiological Sciences. 9 (5): 730–3. doi: 10.1039/b9pp00143c . PMID   20442934.
  5. Schwarz T (December 2005). "Mechanisms of UV-induced immunosuppression" (PDF). The Keio Journal of Medicine. 54 (4): 165–71. doi: 10.2302/kjm.54.165 . PMID   16452825.
  6. Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L, Høgh JK, Hellgren LI, Jemec GB, Agner T, Weidinger S (July 2010). "Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema". Allergy. 65 (7): 911–8. doi:10.1111/j.1398-9995.2010.02326.x. PMID   20132155. S2CID   24679127.
  7. Fluhr JW, Elias PM, Man MQ, Hupe M, Selden C, Sundberg JP, Tschachler E, Eckhart L, Mauro TM, Feingold KR (August 2010). "Is the filaggrin-histidine-urocanic acid pathway essential for stratum corneum acidification?". The Journal of Investigative Dermatology. 130 (8): 2141–4. doi:10.1038/jid.2010.74. PMC   4548931 . PMID   20376063.
  8. Jaffe M (1875). "Ueber die Urocaninsäure" [About urocanic acid]. Berichte der Deutschen Chemischen Gesellschaft (in German). 8 (1): 811–813. doi:10.1002/cber.187500801267.
  9. Jaffe M (1874). "Ueber einen neuen Bestandtheil des Hundeharns" [Concerning a new constituent in the urine of dogs]. Berichte der Deutschen Chemischen Gesellschaft (in German). 7 (2): 1669–1673. doi:10.1002/cber.187400702225.