Urocanic acid (formally ''trans''-Urocanic acid) is an intermediate in the

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipid ...

of L-

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

. 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 Urocanase (also known as imidazolonepropionate hydrolase or urocanate hydratase) is the enzyme () that catalyzes the second step in the degradation of histidine, the hydration of urocanate into imidazolonepropionate. Urocanase is coded for by the ...

(or urocanase) to 4-imidazolone-5-propionic acid and subsequently to

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

Clinical significance

Inherited deficiency of urocanase leads to elevated levels of urocanic acid in the urine, a condition known as

urocanic aciduria Urocanic aciduria is an autosomal recessive metabolic disorder caused by a deficiency of the enzyme urocanase. It is a secondary disorder of histidine metabolism.''Disorders of histidine metabolism.''http://www.ommbid.com/OMMBID/the_online_metabol ...

. An important role for the onset of

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin. Atopic dermatitis is also often called simply eczema but the same term is also used to refer to dermatitis, the larger group of skin conditi ...

and asthma has been attributed to

filaggrin Filaggrin (filament aggregating protein) 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 termin ...

, a skin precursor of urocanic acid. Urocanic acid is thought to be a significant attractant of the nematode parasite ''

Strongyloides stercoralis ''Strongyloides stercoralis'' is a human pathogenic parasitic roundworm causing the disease strongyloidiasis. Its common name in the US is threadworm. In the UK and Australia, however, the term ''threadworm'' can also refer to nematodes of t ...

'', 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. Concentration does not link with age, sex, skin tone, photosensitivity, and stratum corneum thickness. Among other functions, urocanic acid acts as an endogenous sunscreen or photoprotectant against

UVB Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of the ...

-induced DNA damage. However, some studies have questioned this. Urocanic acid is found predominantly in the

stratum corneum The stratum corneum (Latin language, Latin for 'horny layer') is the outermost layer of the epidermis (skin), epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is ...

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). The cis form is known to activate

regulatory T cells The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain immune tolerance, tolerance to self-antigens, and prevent autoimmune disease. Treg ...

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

History

Urocanic acid was first isolated in 1874 by the chemist Max Jaffé from the urine of a dog, hence the name ( = urine, and ''canis'' = dog).

References

External links