Allantoin

Allantoin is a chemical compound with formula C₄H₆N₄O₃. It is also called 5-ureidohydantoin or glyoxyldiureide.<ref>Template:Cite web</ref><ref>Template:Cite web</ref> It is a diureide of glyoxylic acid. Allantoin is a major metabolic intermediate in most organisms including animals, plants and bacteria, though not humans. It is produced from uric acid, which itself is a degradation product of nucleic acids, by action of urate oxidase (uricase).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Allantoin also occurs as a natural mineral compound (IMA symbol Aan<ref>Template:Cite journal</ref>).

History

Allantoin was first isolated in 1800 by the Italian physician Michele Francesco Buniva (1761–1834) and the French chemist Louis Nicolas Vauquelin, who mistakenly believed it to be present in the amniotic fluid.<ref>See:

• Buniva and Vauquelin (1800) "Sur l'eau de l'amnios de femme et de vache" (On the amniotic fluid of women and cows), Annales de chimie, 33 : 269-282.
• See also: Leopold Gmelin with Henry Watts, trans., Hand-book of Chemistry (London, England: The Cavendish Society, 1856), vol. 10, p. 260.</ref> In 1821, the French chemist Jean Louis Lassaigne found it in the fluid of the allantois; he called it "l'acide allantoique".<ref>Lassaigne (1821) "Nouvelles recherches sur la composition les eaux de l'allantoïde et de l'amnios de la vache" (New investigations into the composition of the allantoic and amniotic fluids of the cow), Annales de chimie et de physique, 2nd series, 17 : 295-305. On pp. 300 ff, Lassaigne names and characterizes "l'acide allantoique" (allantoic acid).</ref> In 1837, the German chemists Friedrich Wöhler and Justus Liebig synthesized it from uric acid and renamed it "allantoïn".<ref>See:
• Liebig and Wöhler (1837) "Ueber die Natur der Harnsäure" (On the nature of uric acid), Annalen der Physik und Chemie, 41 (8) : 561-569. Allantoin is named on p. 563. From p. 563: "Sie sind Allantoïssäure, oder dieselbe Substance, die man in der Allantoïsflussigkeit der Kühe gefunden hat; wir werden sie von nun an Allantoïn nennen." (They [i.e., the crystals previously isolated] are allantois acid, or the same substance that one found in the allantois fluid of cows; we will call it "allantoin" from now on.)
• Reprinted in: F. Wöhler and J. Liebig (1838) "Untersuchungen über die Natur der Harnsäure" (Investigations into the nature of uric acid), Annalen der Pharmacie, 26 : 241-340.</ref>

Animals

Named after the allantois (an amniote embryonic excretory organ in which it concentrates during development in most mammals except humans and other hominids), it is a product of oxidation of uric acid by purine catabolism. After birth, it is the predominant means by which nitrogenous waste is excreted in the urine of these animals.<ref>Template:Cite journal</ref> In humans and other higher apes, the metabolic pathway for conversion of uric acid to allantoin is not present, so the former is excreted. Recombinant rasburicase is sometimes used as a drug to catalyze this metabolic conversion in patients. In fish, allantoin is broken down further (into ammonia) before excretion.<ref>Template:Cite journal</ref>

Allantoin has been shown to improve insulin resistance when administered to rats and to increase lifespan when administered to the nematode worm Caenorhabditis elegans.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Bacteria

In bacteria, purines and their derivatives (such as allantoin) are used as secondary sources of nitrogen under nutrient-limiting conditions. Their degradation yields ammonia, which can then be utilized.<ref>Template:Cite journal</ref> For instance, Bacillus subtilis is able to utilize allantoin as its sole nitrogen source.<ref>Template:Cite journal</ref>

Mutants in the B. subtilis pucI gene were unable to grow on allantoin, indicating that it encodes an allantoin transporter.<ref>Template:Cite journal</ref>

In Streptomyces coelicolor, allantoinase (EC 3.5.2.5) and allantoicase (EC 3.5.3.4) are essential for allantoin metabolism. In this species the catabolism of allantoin, and the subsequent release of ammonium, inhibits antibiotic production (Streptomyces species synthesize about half of all known antibiotics of microbial origin).<ref>Template:Cite journal</ref>

Applications

Allantoin is present in botanical extracts of the comfrey plant and in the urine of most mammals. Chemically synthesized bulk allantoin, which is chemically equivalent to natural allantoin, is safe, non-toxic, compatible with cosmetic raw materials and meets CTFA and JSCI requirements. Over 10,000 patents reference allantoin.<ref>Patent Lens searchTemplate:Dead link</ref>

Cosmetics

Manufacturers may use allantoin as an ingredient in over-the-counter cosmetics.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Pharmaceuticals

It is frequently present in toothpaste, mouthwash, and other oral hygiene products, in shampoos, lipsticks, anti-acne products, sun care products, and clarifying lotions, various cosmetic lotions and creams, and other cosmetic and pharmaceutical products.<ref>Template:Cite journal</ref>

Biomarker of oxidative stress

Since uric acid is the end product of the purine metabolism in humans, only non-enzymatic processes with reactive oxygen species will give rise to allantoin, which is thus a suitable biomarker to measure oxidative stress in chronic illnesses and senescence.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

See also

• Imidazolidinyl urea and diazolidinyl urea, are antimicrobial condensation products of allantoin with formaldehyde.

External links

• E. coli Allantoinase (AllB) in Uniprot (P77671)
• GMD MS Spectrum