Allantoin is a chemical compound with formula C₄H₆N₄O₃. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a

diureide Acylureas (also called ''N''-acylureas or ureides) are a class of chemical compounds formally derived from the acylation of urea. Uses Insecticides A subclass of acylureas known as benzoylureas are insecticides. They act as insect growth regul ...

glyoxylic acid Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially. ...

. 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 Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...

, by action of urate oxidase (uricase). The occurs as a natural mineral compound ( IMA

symbol A symbol is a mark, sign, or word that indicates, signifies, or is understood as representing an idea, object, or relationship. Symbols allow people to go beyond what is known or seen by creating linkages between otherwise very different conc ...

Aan).

History

Allantoin was first isolated in 1800 by the Italian physician Michele Francesco Buniva (1761–1834) and the French chemist

Louis Nicolas Vauquelin Prof. Louis Nicolas Vauquelin FRS(For) HFRSE (16 May 1763 – 14 November 1829) was a French pharmacist and chemist. He was the discoverer of both chromium and beryllium. Early life Vauquelin was born at Saint-André-d'Hébertot in Normandy, F ...

, who mistakenly believed it to be present in the

amniotic fluid The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products between ...

. In 1821, the French chemist

Jean Louis Lassaigne Jean Louis Lassaigne (22 September 1800 – 18 March 1859) was a French chemist. He is best known for the sodium fusion test named after him. Early life Lassaigne was born in Paris. Initially he worked in the laboratory of Louis Nicolas Vauquelin ...

found it in the fluid of the

allantois The allantois (plural ''allantoides'' or ''allantoises'') is a hollow sac-like structure filled with clear fluid that forms part of a developing amniote's conceptus (which consists of all embryonic and extraembryonic tissues). It helps the embryo ...

; he called it ''"l'acide allantoique"''. In 1837, the German chemists

Friedrich Wöhler Friedrich Wöhler () FRS(For) Hon FRSE (31 July 180023 September 1882) was a German chemist known for his work in inorganic chemistry, being the first to isolate the chemical elements beryllium and yttrium in pure metallic form. He was the fi ...

and Justus Liebig synthesized it from

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...

and renamed it "allantoïn".

Animals

Named after the

(an

amniote Amniotes are a clade of tetrapod vertebrates that comprises sauropsids (including all reptiles and birds, and extinct parareptiles and non-avian dinosaurs) and synapsids (including pelycosaurs and therapsids such as mammals). They are dis ...

embryonic excretory organ in which it concentrates during development in most

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...

s except humans and other hominids), it is a product of oxidation of

purine Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines ...

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, li ...

. After birth, it is the predominant means by which

nitrogenous waste Metabolic wastes or excrements are substances left over from metabolic processes (such as cellular respiration) which cannot be used by the organism (they are surplus or toxic), and must therefore be excreted. This includes nitrogen compounds, ...

is excreted in the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...

of these animals. In humans and other higher apes, the metabolic pathway for conversion of

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 Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...

) before excretion. Allantoin has been shown to improve insulin resistance when administered to rats and to increase lifespan when administered to the nematode worm ''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

''.

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. For instance, ''

Bacillus subtilis ''Bacillus subtilis'', known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacillus ...

'' is able to utilize allantoin as its sole nitrogen source. Mutants in the ''B. subtilis'' ''pucI'' gene were unable to grow on allantoin, indicating that it encodes an allantoin transporter. In ''

Streptomyces coelicolor ''Streptomyces albidoflavus'' is a bacterium species from the genus of ''Streptomyces'' which has been isolated from soil from Poland. ''Streptomyces albidoflavus'' produces dibutyl phthalate and streptothricins. Small noncoding RNA Bacter ...

'', 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).

Applications

Allantoin is present in botanical

extract An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures, absolutes or in powder form. The aromatic principles of many spices, nuts ...

s of the

comfrey ''Symphytum'' is a genus of flowering plants in the borage family, Boraginaceae, known by the common name comfrey (pronounced ). There are 59 recognized species.WFO (2022): Symphytum L. Published on the Internet; http://www.worldfloraonline.org/ ...

plant and in the

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

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A ...

s reference allantoin.

Cosmetics and toiletries

Manufacturers cite several beneficial effects for allantoin as an active ingredient in over-the-counter cosmetics, including: a moisturizing and keratolytic effect, increasing the water content of the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...

and enhancing the

desquamation Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is . Physiologic desquamation Keratinocytes are the predominant cells of the epidermis, the outermost layer of the skin. Living keratinocytes reside in ...

of upper layers of dead skin cells, increasing the smoothness of the skin; promoting cell proliferation and

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...

; and a soothing, anti-irritant, and skin protectant effect by forming complexes with irritant and sensitizing agents. An animal study in 2010 found that based on the results from

histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...

analyses, a soft lotion with 5% allantoin ameliorates the

process, by modulating the inflammatory response. The study also suggests that quantitative analysis lends support to the idea that allantoin also promotes

fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...

proliferation and synthesis of the

. A study published in 2009 reported the treatment of

pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

in mild-to-moderate

atopic dermatitis 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 often thickens over tim ...

with a topical nonsteroidal agent containing allantoin.

Pharmaceuticals

It is frequently present in

toothpaste Toothpaste is a paste or gel dentifrice used with a toothbrush to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it is an abrasive that aids in removing dental plaque and food from the teeth, ...

mouthwash Mouthwash, mouth rinse, oral rinse, or mouth bath is a liquid which is held in the mouth passively or swilled around the mouth by contraction of the perioral muscles and/or movement of the head, and may be gargled, where the head is tilted back ...

, and other

oral hygiene Oral hygiene is the practice of keeping one's mouth clean and free of disease and other problems (e.g. bad breath) by regular brushing of the teeth (dental hygiene) and cleaning between the teeth. It is important that oral hygiene be carried ou ...

products, in

shampoo Shampoo () is a hair care product, typically in the form of a viscous liquid, that is used for cleaning hair. Less commonly, shampoo is available in solid bar format. Shampoo is used by applying it to wet hair, massaging the product into the ...

lipstick Lipstick is a cosmetic product used to apply coloration and texture to lips, often made of wax and oil. Different pigments are used to produce color, and minerals such as silica may be used to provide texture. The use of lipstick dates bac ...

s, anti-acne products, sun care products, and clarifying lotions, various cosmetic lotions and creams, and other cosmetic and pharmaceutical products.

Biomarker of oxidative stress

Since

is the end product of the

purine metabolism Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms. Biosynthesis Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ...

in humans, only non-enzymatic processes with

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

will give rise to allantoin, which is thus a suitable

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...

to measure

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

in chronic illnesses and

senescence Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence invol ...

References

{{reflist

External links

* '' E. coli'
Allantoinase
(AllB) in

Uniprot UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from ...

P77671

GMD MS Spectrum
Cosmetics chemicals Ureas Excipients Hydantoins