Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide.[1][2] It is a
diureide of
glyoxylic acid. Allantoin is a major metabolic intermediate in most organisms including animals, plants and bacteria. It is produced from
uric acid, which itself is a degradation product of
nucleic acids, by action of
urate oxidase (uricase).[3][4][5] Allantoin also occurs as a natural mineral compound (
IMAsymbol Aan[6]).
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.[7] In 1821, the French chemist
Jean Louis Lassaigne found it in the fluid of the
allantois; he called it "l'acide allantoique".[8] In 1837, the German chemists
Friedrich Wöhler and
Justus Liebig synthesized it from
uric acid and renamed it "allantoïn".[9]
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
purinecatabolism. After birth, it is the predominant means by which
nitrogenous waste is excreted in the
urine of these animals.[10] 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.[11]
Allantoin has been shown to improve insulin resistance when administered to rats and to increase lifespan when administered to the nematode worm Caenorhabditis elegans.[12][13]
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.[14] For instance, Bacillus subtilis is able to utilize allantoin as its sole nitrogen source.[15]
Mutants in the B. subtilispucI gene were unable to grow on allantoin, indicating that it encodes an allantoin transporter.[16]
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).[17]
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.[18]
Cosmetics
Manufacturers may use allantoin as an ingredient in over-the-counter cosmetics.[citation needed]
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.[19]
^Pizzichini, Maria; Pandolfi, Maria Luisa; Arezzini, Laura; Terzuoli, Lucia; Fè, Linda; Bontemps, Francois; Van den Berghe, Georges; Marinello, Enrico (1996-08-09). "Labelling of uric acid and allantoin in different purine organs and urine of the rat". Life Sciences. 59 (11): 893–899.
doi:
10.1016/0024-3205(96)00387-6.
PMID8795700.
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.)
^Kanďár R, Záková P (2008). "Allantoin as a marker of oxidative stress in human erythrocytes". Clinical Chemistry and Laboratory Medicine. 46 (9): 1270–4.
doi:
10.1515/CCLM.2008.244.
PMID18636793.
S2CID6420729.
^Zitnanová I, Korytár P, Aruoma OI, Sustrová M, Garaiová I, Muchová J, Kalnovicová T, Pueschel S, Duracková Z (2004). "Uric acid and allantoin levels in Down syndrome: Antioxidant and oxidative stress mechanisms?". Clinica Chimica Acta. 341 (1–2): 139–46.
doi:
10.1016/j.cccn.2003.11.020.
PMID14967170.