Allantoin

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Allantoin
Allantoin.svg
Allantoine.JPG
Allantoin-3D-balls.png
Names
IUPAC name
N-(2,5-Dioxoimidazolidin-4-yl)urea
Other names
1-(2,5-Dioxoimidazolidin-4-yl)urea
Glyoxyldiureide
5-Ureidohydantoin
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.002.358 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 202-592-8
KEGG
PubChem CID
RTECS number
  • YT1600000
UNII
  • InChI=1S/C4H6N4O3/c5-3(10)6-1-2(9)8-4(11)7-1/h1H,(H3,5,6,10)(H2,7,8,9,11) Yes check.svgY
    Key: POJWUDADGALRAB-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C4H6N4O3/c5-3(10)6-1-2(9)8-4(11)7-1/h1H,(H3,5,6,10)(H2,7,8,9,11)
    Key: POJWUDADGALRAB-UHFFFAOYAE
  • O=C1NC(=O)NC1NC(=O)N
  • C1(C(=O)NC(=O)N1)NC(=O)N
Properties
C4H6N4O3
Molar mass 158.117 g·mol−1
Appearancecolourless crystalline powder
Odor odorless
Density 1.45 g/cm3
Melting point 230 °C (446 °F; 503 K) (decomposes)
Boiling point 478 °C (892 °F; 751 K) [ dubious – discuss ]
0.57 g/100 mL (25 °C)
4.0 g/100 mL (75 °C)
Solubility soluble in alcohol, pyridine, NaOH
insoluble in ethyl ether
log P −3.14
Acidity (pKa)8.48
Hazards
NFPA 704 (fire diamond)
2
1
0
Lethal dose or concentration (LD, LC):
> 5000 mg/kg (oral, rat)
Safety data sheet (SDS) Allantoin MSDS
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 ?)

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] The occurs as a natural mineral compound (IMA symbol Aan [6] ).

Contents

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 purine catabolism. 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]

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. [20] [21]

See also

Related Research Articles

<span class="mw-page-title-main">Uric acid</span> Organic compound

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 of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.

<span class="mw-page-title-main">Gout</span> Medical condition that results in recurrent pain and swelling of joints

Gout is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crystals. Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours. The joint at the base of the big toe is affected (Podagra) in about half of cases. It may also result in tophi, kidney stones, or kidney damage.

<span class="mw-page-title-main">Xanthine oxidase</span> Class of enzymes

Xanthine oxidase is a form of xanthine oxidoreductase, a type of enzyme that generates reactive oxygen species. These enzymes catalyze the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid. These enzymes play an important role in the catabolism of purines in some species, including humans.

<span class="mw-page-title-main">Excretion</span> Elimination by an organism of metabolic waste products

Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell. Excretion is an essential process in all forms of life. For example, in mammals, urine is expelled through the urethra, which is part of the excretory system. In unicellular organisms, waste products are discharged directly through the surface of the cell.

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

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off (lysed) from the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias and in particular when treating non-Hodgkin lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia. This is a potentially fatal complication and patients at increased risk for TLS should be closely monitored while receiving chemotherapy and should receive preventive measures and treatments as necessary. TLS can also occur on its own although this is less common.

<span class="mw-page-title-main">Urate oxidase</span> Pseudogene in the species Homo sapiens

The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:

<span class="mw-page-title-main">Lesch–Nyhan syndrome</span> Rare genetic disorder

Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the HPRT1 gene located on the X chromosome. LNS affects about 1 in 380,000 live births. The disorder was first recognized and clinically characterized by American medical student Michael Lesch and his mentor, pediatrician William Nyhan, at Johns Hopkins.

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

Rasburicase is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is known to be present in many mammals but does not naturally occur in humans. Rasburicase is produced by a genetically modified Saccharomyces cerevisiae strain. The complementary DNA (cDNA) coding for rasburicase was cloned from a strain of Aspergillus flavus.

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

Alloxan, sometimes referred to as alloxan hydrate, is the name of the organic compound with the formula OC(N(H)CO)2C(OH)2. It is classified as a derivative of pyrimidine. The anhydrous derivative OC(N(H)CO)2CO is also known, as well as a dimeric derivative. These are some of the earliest known organic compounds. They exhibit a variety of biological activities.

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

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

Adenylosuccinate lyase is an enzyme that in humans is encoded by the ADSL gene.

<span class="mw-page-title-main">Ribose-phosphate diphosphokinase</span> Class of enzymes

Ribose-phosphate diphosphokinase is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under EC 2.7.6.1.

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

The Lysine riboswitch is a metabolite binding RNA element found within certain messenger RNAs that serve as a precision sensor for the amino acid lysine. Allosteric rearrangement of mRNA structure is mediated by ligand binding, and this results in modulation of gene expression. Lysine riboswitch are most abundant in Bacillota and Gammaproteobacteria where they are found upstream of a number of genes involved in lysine biosynthesis, transport and catabolism. The lysine riboswitch has also been identified independently and called the L box.

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

Allantoicase is an enzyme (EC 3.5.3.4) that in humans is encoded by the ALLC gene. Allantoicase catalyzes the chemical reaction

<span class="mw-page-title-main">Purine nucleotide cycle</span>

The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. AMP coverts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then coverts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.

In molecular biology 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase EC 4.1.1.n1 is an enzyme involved in purine catabolism. It catalyses the decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) into S(+)-allantoin. It is the third step of the conversion of uric acid to allantoin. Step one is catalysed by urate oxidase and step two is catalysed by hydroxyisourate hydrolase.

The Nucleobase cation symporter-2 (NCS2) family, also called the Nucleobase ascorbate transporter (NAT) family, consists of over 1000 sequenced proteins derived from gram-negative and gram-positive bacteria, archaea, fungi, plants and animals. The NCS2/NAT family is a member of the APC Superfamily of secondary carriers. Of the five known families of transporters that act on nucleobases, NCS2/NAT is the only one that is most widespread. Many functionally characterized members are specific for nucleobases including both purines and pyrimidines, but others are purine-specific. However, two closely related rat/human members of the family, SVCT1 and SVCT2, localized to different tissues of the body, co-transport L-ascorbate (vitamin C) and Na+ with a high degree of specificity and high affinity for the vitamin. Clustering of NCS2/NAT family members on the phylogenetic tree is complex, with bacterial proteins and eukaryotic proteins each falling into at least three distinct clusters. The plant and animal proteins cluster loosely together, but the fungal proteins branch from one of the three bacterial clusters forming a tighter grouping. E. coli possesses four distantly related paralogous members of the NCS2 family.

In molecular biology, the SR1 RNA is a small RNA (sRNA) produced by species of Bacillus and closely related bacteria. It is a dual-function RNA which acts both as a protein-coding RNA and as a regulatory sRNA.

Bacillus fastidiosus is an aerobic, motile, rod-shaped bacterium that has been isolated from soil and poultry litter. The species was first isolated and described by the scientist Den Dooren de Jong in 1929. This organism is a mesophile that contains ellipsoidal spores that do not cause swelling of the sporangia. Bacillus fastidiosus is only able to grow in the presence of uric acid, allantoin, or allantoic acid.

References

  1. ↑ "Allantoin".
  2. ↑ "CAS # 97-59-6, Allantoin, 5-Ureidohydantoin, Glyoxyldiureide, Glyoxylic diureide, Cordianine, Glyoxyldiureid, (2,5-Dioxo-4-imidazolidinyl)urea".
  3. ↑ 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. PMID   8795700.
  4. ↑ Xi, H.; Schneider, B. L.; Reitzer, L. (2000-10-01). "Purine catabolism in Escherichia coli and function of xanthine dehydrogenase in purine salvage". Journal of Bacteriology. 182 (19): 5332–5341. doi:10.1128/jb.182.19.5332-5341.2000. ISSN   0021-9193. PMC   110974 . PMID   10986234.
  5. ↑ Johnson, Richard J.; Sautin, Yuri Y.; Oliver, William J.; Roncal, Carlos; Mu, Wei; Gabriela Sanchez-Lozada, L.; Rodriguez-Iturbe, Bernardo; Nakagawa, Takahiko; Benner, Steven A. (2009-01-01). "Lessons from comparative physiology: could uric acid represent a physiologic alarm signal gone awry in western society?". Journal of Comparative Physiology B. 179 (1): 67–76. doi:10.1007/s00360-008-0291-7. ISSN   1432-136X. PMC   2684327 . PMID   18649082.
  6. ↑ Warr, L.N. (2021). "IMA-CNMNC approved mineral symbols". Mineralogical Magazine. 85 (3): 291–320. Bibcode:2021MinM...85..291W. doi: 10.1180/mgm.2021.43 . S2CID   235729616.
  7. ↑ 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.
  8. ↑ 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).
  9. ↑ 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.
  10. ↑ Young E. G.; Wentworth H. P.; Hawkins W. W. (1944). "The absorption and excretion of allantoin in mammals". J. Pharmacol. Exp. Ther. 81 (1): 1–9.
  11. ↑ Fujiwara, S; Noguchi T (1995). "Degradation of purines: only ureidoglycollate lyase out of four allantoin-degrading enzymes is present in mammals". The Biochemical Journal. 312 (Pt 1): 315–8. doi:10.1042/bj3120315. PMC   1136261 . PMID   7492331.
  12. ↑ Ko, W.C.; Liu, I.M.; Chung, H.H.; Cheng, J.T. (2008). "Activation of I2-imidazoline receptors may ameliorate insulin resistance in fructose-rich chow-fed rats". Neuroscience Letters. 448 (1): 90–93. doi:10.1016/j.neulet.2008.10.002. PMID   18926881. S2CID   207127849.
  13. ↑ Shaun Calvert; Robi Tacutu; Samim Sharifi; Rute Teixeira; Pratul Ghosh; João Pedro de Magalhães (2016). "A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans". Aging Cell. 15 (2): 256–266. doi:10.1111/acel.12432. PMC   4783339 . PMID   26676933.
  14. ↑ Ma, Pikyee; Patching, Simon G.; Ivanova, Ekaterina; Baldwin, Jocelyn M.; Sharples, David; Baldwin, Stephen A.; Henderson, Peter J. F. (2016-05-01). "Allantoin transport protein, PucI, from Bacillus subtilis: evolutionary relationships, amplified expression, activity and specificity". Microbiology. 162 (5): 823–836. doi:10.1099/mic.0.000266. ISSN   1465-2080. PMC   4851255 . PMID   26967546.
  15. ↑ Goelzer, Anne; Bekkal Brikci, Fadia; Martin-Verstraete, Isabelle; Noirot, Philippe; Bessières, Philippe; Aymerich, Stéphane; Fromion, Vincent (2008-02-26). "Reconstruction and analysis of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis". BMC Systems Biology. 2: 20. doi:10.1186/1752-0509-2-20. ISSN   1752-0509. PMC   2311275 . PMID   18302748.
  16. ↑ Schultz, A. C.; Nygaard, P.; Saxild, H. H. (2001-06-01). "Functional analysis of 14 genes that constitute the purine catabolic pathway in Bacillus subtilis and evidence for a novel regulon controlled by the PucR transcription activator". Journal of Bacteriology. 183 (11): 3293–3302. doi:10.1128/JB.183.11.3293-3302.2001. ISSN   0021-9193. PMC   99626 . PMID   11344136.
  17. ↑ Navone, Laura; Casati, Paula; Licona-Cassani, Cuauhtémoc; Marcellin, Esteban; Nielsen, Lars K.; Rodriguez, Eduardo; Gramajo, Hugo (2013-11-29). "Allantoin catabolism influences the production of antibiotics in Streptomyces coelicolor". Applied Microbiology and Biotechnology. 98 (1): 351–360. doi:10.1007/s00253-013-5372-1. hdl: 11336/7859 . ISSN   0175-7598. PMID   24292080. S2CID   216898.
  18. ↑ Patent Lens search [ permanent dead link ]
  19. ↑ Thornfeldt, C (2005). "Cosmeceuticals containing herbs: fact, fiction, and future". Dermatologic Surgery. 31 (7 Pt 2): 873–80. doi:10.1111/j.1524-4725.2005.31734. PMID   16029681.
  20. ↑ 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. PMID   18636793. S2CID   6420729.
  21. ↑ 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. PMID   14967170.
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