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Orotic acid

General Description Metabolism Applications References
Orotic acid
Orotic acid structure
CAS No.
65-86-1
Chemical Name:
Orotic acid
Synonyms
Orodin;Oropur;orotic;Orotyl;Orotonin;Oroturic;H-ORO-OH;Orotonsan;Orotsaure;orodin[qr]
CBNumber:
CB5691265
Molecular Formula:
C5H4N2O4
Formula Weight:
156.1
MOL File:
65-86-1.mol

Orotic acid Properties

Melting point:
>300°C
Boiling point:
280.29°C (rough estimate)
Density 
1.6814 (rough estimate)
refractive index 
1.4800 (estimate)
pka
pK1:1.8(+1);pK2:9.55(0) (25°C)
form 
Crystalline Powder
color 
White
Water Solubility 
Slightly soluble
Merck 
13,6942
BRN 
383901
Stability:
Stable. Incompatible with strong oxidizing agents.
InChIKey
PXQPEWDEAKTCGB-UHFFFAOYSA-N
CAS DataBase Reference
65-86-1(CAS DataBase Reference)
NIST Chemistry Reference
Orotic acid(65-86-1)
EPA Substance Registry System
Orotic acid (65-86-1)
SAFETY
  • Risk and Safety Statements
Symbol(GHS) 
GHS07
Signal word  Warning
Hazard statements  H302-H315-H319-H335
Precautionary statements  P280a-P301+P312a-P321-P332+P313-P501a-P261-P305+P351+P338
Hazard Codes  Xn,Xi
Risk Statements  22-36/37/38
Safety Statements  26-36/37/39-22-37/39
WGK Germany  3
RTECS  RM3180000
10-21
Hazard Note  Harmful
TSCA  Yes
HS Code  29335990

Orotic acid price More Price(3)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich O2750 Orotic acid ≥98% (titration), anhydrous 65-86-1 10g $46.9 2019-12-02 Buy
Alfa Aesar B25349 Orotic acid, anhydrous, 97% 65-86-1 100g $86.6 2019-12-02 Buy
Alfa Aesar B25349 Orotic acid, anhydrous, 97% 65-86-1 500g $235 2019-12-02 Buy

Orotic acid Chemical Properties,Uses,Production

General Description

Orotic acid (also known as pyrimidinecarboxylic acid) is a heterocyclic acid; it is also known as. Historically it was believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin. It is well known as a precursor in biosynthesis of pyrimidines; in mammals it is released from the mitochondrial dihydroorotate dehydrogenase (DHODH) for conversion to UMP by the cytoplasmic UMP synthase enzyme[1]. OA is also a normal part of the diet, being found in milk and dairy products[5], and it is converted to uridine for use in the pyrimidine salvage pathway predominantly in liver, kidney and erythrocytes. Before its essential role as an intermediate of pyrimidine biosynthesis was established in the 1950s[3], the compound OA was discovered in whey (Greek oros) by Biscaro and Belloni (1905)[4]. Since then it has received attention from several different aspects. For example, it is proposed that the dietary orotate is beneficial for animals and humans obviously arose from its considerable natural amounts in milk and dairy products[5]. In addition, it also draw great attention from its medical potentials such as improvement of learning behavior of adult rats, neuro-protective effect for gerbils and cats under transient cerebral ischemia, and optimization of functions in normal and ischemic rat hearts[6-9].

Metabolism

Orotate [orotic acid, OA] is the product of dihydroorotate dehydrogenase [DHODH], the fourth enzyme of pyrimidine [UMP] de novo synthesis [Fig. 1]. It is abundant in the serum and particularly urine of patients suffering from hereditary orotic academia or from enzyme defects in the urea cycle[10]. The sequence of six chemical reactions of UMP de novo synthesis is conserved from microorganisms to humans [Figure 1], although the organization of enzymes involved is different in eukaryotes[11-13]. In mammals, the six enzymes are coded by only three genes. The tri-functional CAD enzyme and the bifunctional UMP synthase each contain their appropriate catalytic activities on one polypeptide chain. The product of the third gene, dihydroorotate dehydrogenase [DHODH] holds a mitochondrial targeting sequence and a transmembrane domain at the N-terminus, which enable the enzyme to find its place in the inner mitochondrial membrane[14]. Through its electron acceptor, ubiquinone, DHODH is functionally united with the respiratory chain and can contribute to energy conservation in mitochondria. In turn, the formation of orotic acid [OA] by mitochondria, and hence the de novo synthesis of UMP, is strictly aerobic. In growth processes OA can be considered as a metabolic link between environmental oxygen tension and the proliferative capacity of cells[15].

Applications

Overview
Orotic Acid is used in the preparation of therapeutic agents for chronic obstructive pulmonary disease [COPD] treatment[16]. As it is an intermediate in de novo pyrimidine biosynthesis, it may be used to study the specificity and kinetics of orotate phosphoribosyltransferase [OPRT] which catalyzes the reversible phosphoribosyl transfer from 5′-phospho-α-d-ribose 1′-diphosphate [PRPP] to orotic acid [OA], forming pyrophosphate and orotidine 5′-monophosphate [OMP][17]. Orotic acid can also be used as a starting material for the potential commercial bio-production of uridine 5′-monophosphate [UMP] by microbes such as Corynebacterium ammoniagenes [ATCC 6872] or Saccharomyces cerevisiae. Moreover, it may be used to study the AMPK/SREBP-1 dependent cell-signaling pathway and transcription regulation mechanisms associated with the induction hepatic lipogenesis[17].
Medical aspects
OA has strong pharmacological potentials. The improvement of learning behavior of adult rats, neuro-protective effect for gerbils and cats under transient cerebral ischemia, and optimization of functions in normal and ischemic rat hearts were generally assigned to the precursor role of OA in cells for pyrimidine nucleotides and RNA[6-9]. The development of complexes and salts with metal ions [Mg2+, Zn2+, Ca2+, K+] and organic cations [e.g. choline, carnitine] exploited the favorable carrier function of OA for transportation and delivery of these ligands in living organisms to compensate deficiency syndromes[5]. Likewise, the construction of platinum, palladium and tin coordination compounds with OA for administration in cancer chemotherapy followed this principle[18]. The positive impact of OA preparations claimed for humans are highlighted by promises given in the public domain, such as beneficial cardiovascular effects, energy provision, improvement of body composition, and enhanced athletic performance.
Study has also shown that OA may lower the serum cholesterol and lipid[19-21]. Orotic acid also has strong uricosuric effect, originating from its role as a true transport substrate for the anion exchangerURAT1 [encoded by human SLC22A12 gene] located at the luminal site of the tubule cells[22].
Dietary aspects
The assumption that dietary orotate is beneficial for animals and humans obviously arose from its considerable natural amounts in milk and dairy products[5]. In the 1970s OA was proposed to increase the UDP-glucuronate pool for hepatic detoxification of bilirubin in the treatment of neonatal jaundice[5]. Another, underestimated, benefit of OA in the diet of newborns may be the establishment of the anaerobic OA-degrading intestinal microflora. Overall, it has strong potential to become a growth-enhancer for livestock.
Central Nervous systems
OA’s benefit for the brain, mentioned earlier, deserves closer attention. It can be assumed that a continuous supply of pyrimidine nucleotides is essential not only for the developing central nervous system[23], but equally for its plasticity, regeneration and neurotransmission: for example, some metabotropic P2Y receptor subtypes are sensitive to uridine nucleotides[24]. OA has putative protective and improvement effects of pyrimidine nucleotide pools, RNA synthesis, receptor saturation, repairing of ischeamia-induced membrane damage, which is explained by the function of OA as an intermediate in de novo UMP synthesis[25, 26].
Research field
OA had became a compound of considerable interest as a tool for studying pyrimidine metabolism in cells, tissues and animals: monitoring precursors, nucleotide pools and the rate of RNA synthesis, differentiating between de novo and salvage/recycling pathways, searching for antimetabolites and anticancer drugs[27, 29]. Concurrently, the growth-promoting features of OA were still of interest, and OA was used on animals and humans, with various biochemical rationales, assumptions and expectations[28, 30]. When OA was an additive to pharmaceutical preparations, its benefits were attributed to its being an intermediate of pyrimidine biosynthesis and therefore augmenting uridine nucleotide pools which are required for nucleic acid synthesis and for all pyrimidine nucleotide dependent biosynthetic processes[31, 32].

References

  1. https://www.springer.com/us/book/9780852002940
  2. Löffler, M.; Carrey E.; Zameitat, E. Orotic acid, more than just an intermediate of pyrimidine de novo synthesis, J. Genet. Genomics 2015, 42, 207–219.
  3. Reichard P.; Lagerkvist, U. The biogenesis of orotic acid in liver slices, Acta Chem. Scand. 1953, 7, 1207–1217.
  4. Biscaro, G.; Belloni E. About a new compound of the milk, Annuario della Soc. Chimica di Milano 1905, 11, 15.
  5. Löffler, M.; Carrey E.; Zameitat, E. Orotic acid,more than just an intermediate of pyrimidine de novo synthesis, J. Genet. Genomics 2015, 42, 207–219.
  6. Ru?thrich, H.; Wetzel, W.; Matthies, H. Postnatal orotate treatment: effects on learning and memory in adult rats, Psychopharmacology 1979, 63, 25–28.
  7. Krug, M.; Koch, M.; Schoof, E.; Wagner, M.; Matthies, H. Methylglucamine orotate, a memory-improving drug, prolongs hippocampal long-term potentiation, Eur. J. Pharmacol. 1989, 173, 223–226.
  8. Akiho, H.; Iwai, A.; Katoh-Sudoh,M.; Tsukamoto, S.; Koshiya, K.; Yamaguchi, T. Neuroprotective effect of Y-39558, orotic acid ethylester, in gerbil forebrain ischemia, Jpn. J. Pharmacol. 1998, 76, 441–444.
  9. Vilskersts, R.; Liepinsh, E.; Kuka, J.; Cirule, H.; Veveris, M.; Kalvinsh, I.; Dambrova, M. Myocardial infarct size-limiting and anti-arrhythmic effects of mildronate orotate in the rat heart, Cardiovasc. Drug Ther. 2009, 21, 281–288.
  10. Webster, D.R., Becroft, D.M., van Gennip, A.H., van Kuilenburg, A.B.P., 2001. Hereditary orotic aciduria and other disorders of pyrimidine metabolism. In: Scriver, C.R., Beaudet, A.L., Sly,W.S., Valle, D. [Eds.], The Metabolic and Molecular Bases of Inherited Disease, Vol. II. Medical Publishing Division, McGraw-Hill, New York, USA, pp. 2663e2702.
  11. Jones, M.E. Pyrimidine nucleotide biosynthesis in animals: genes, enzymes, and regulation of UMP biosynthesis, Ann. Rev. Biochem. 1980, 49, 253–279.
  12. Evans, D.R.; Guy, H.I. Mammalian pyrimidine biosynthesis: fresh insights into an ancient pathway, J. Biol. Chem. 2004, 279, 33035–33038.
  13. LöfflerM.; Zameitat, E.. Pyrimidine biosynthesis and degradation [catabolism] in The Encyclopedia of Biological Chemistry, eds. W.J. Lennarz; M.D. Lane, Academic Press, Waltham, 2013, Vol III, pp. 712–718.
  14. Rawls, J.; Knecht, W.; Diekert, K.; Lill, R.; Löffler, M. Requirements for the mitochondrial import and localization of dihydroorotate dehydrogenase, Eur. J. Biochem. 2000, 267, 2079– 2087.
  15. Löffler, M.; Carrey, E.A.; Zameitat, E. Essential role of mitochondria in pyrimidine metabolism, in Tumor Cell Metabolism: Pathways, Regulation and Biology, eds. S. Mazurek; S. Shoshan, Springer,Wien, Austria, 2015, pp. 287–312
  16. https://www.trc-canada.com/product-detail/?CatNum=O691500&CAS=50887-69-9%20&Chemical_Name=Orotic%20Acid%20Monohydrate&Mol_Formula=C?H?N?O?•H?O
  17. https://www.sigmaaldrich.com/catalog/product/sigma/o2750?lang=en&region=US
  18. Nath, M.; Vats, M.; Roy, P. Tri- and diorganotin[IV] complexes of biologically important orotic acid: synthesis, spectroscopic studies, in vitro anti-cancer, DNA fragmentation, enzyme assays and in vivo anti-inflammatory activities, Eur. J. Med. Chem. 2013, 9, 310–321.
  19. Kelley,W.N.; Greene,M.L.; Fox, I.H.; Rosenbloom, F.M.; Levy R.I.; Seegmiller, J.E. Effects of orotic acid on purine and lipoprotein metabolism in man, Metabolism 1979, 19, 1025–1035.
  20. Robinson, J.L.; Dombrowski, D.B. Effects of orotic acid ingestion on urinary and blood parameters in humans, Nutr. Res. 1983, 3, 407–415.
  21. Robinson, J.K.;Dombrowski,D.B.; Tauss, L.R.; Jones, L.R.Assessment in humans of hypolipidemia induced by orotic acid, Am. J. Clin.Nutr. 1985, 41, 605–608.
  22. Miura,D.;Anzai,N.; Jutabha, P.; Chanluang, S.;He, X.; Toshiyuki, F.; Endou,H.Human urate transporter 1 [hURAT1] mediates the transport of orotate, J. Physiol. Sci. 2011, 61, 253–257.
  23. Connolly, G.P., Duley, J.A., 1999. Uridine and its nucleotides: biological actions, therapeutic potentials. Trends Pharmacol. Sci. 20, 218e225.
  24. Von Ku¨gelen, I., 2006. Pharmacological profiles of cloned mammalian P2Yreceptor subtypes. Pharmacol. Therapeut. 110, 414e432.
  25. Akiho, H., Iwai, A., Katoh-Sudoh, M., Tsukamoto, S., Koshiya, K., Yamaguchi, T., 1997. Post-ischaemic treatment with orotic acid prevented neuronal injury in gerbil brain ischaemia. Neuroreport 8, 607e610.
  26. Akiho, H., Iwai, A., Katoh-Sudoh, M., Tsukamoto, S., Koshiya, K., Yamaguchi, T., 1998a. Neuroprotective effect of Y-39558, orotic acid ethylester, in gerbil forebrain ischemia. Jpn. J. Pharmacol. 76, 441e444.
  27. Heidelberger, C., 1965. Fluorinated pyrimidines. Prog. Nucleic Acid Res. Mol. Biol. 4, 1e50.
  28. O’Sullivan, W.J., 1973. Orotic acid. Aust. N. Z. J. Med. 3, 417e423.
  29. Kaneti, J.J., Golovinsky, E.V., 1971. Quantitative relationships between the electronic structure and biological activity of some analogues of orotic acid. Chem. Biol. Interact. 3, 421e428.
  30. Falk, M., 1985. Orotsa¨ure. Die Pharmazie 40, 377e383
  31. Grisham, C.M., Garrett, R.H., Garrett, R., 2008. Biochemistry. Brooks Cole Publishing, Pacific Grove, USA.
  32. Voet, D., Voet, J.G., 2011. Biochemistry. John Wiley and Sons, New York, USA.

Chemical Properties

white crystalline powder

Uses

hepatoprotectant, uricosuric agent

Uses

An intermediate in de novo pyrimidine biosynthesis.

Definition

ChEBI: A pyrimidinemonocarboxylic acid that is uracil bearing a carboxy substituent at position C-6.

General Description

White crystals or crystalline powder.

Air & Water Reactions

Slightly soluble in water.

Reactivity Profile

Carboxylic acids, such as Orotic acid, donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Carboxylic acids with six or fewer carbon atoms are freely or moderately soluble in water; those with more than six carbons are slightly soluble in water. Soluble carboxylic acid dissociate to an extent in water to yield hydrogen ions. The pH of solutions of carboxylic acids is therefore less than 7.0. Many insoluble carboxylic acids react rapidly with aqueous solutions containing a chemical base and dissolve as the neutralization generates a soluble salt. Carboxylic acids in aqueous solution and liquid or molten carboxylic acids can react with active metals to form gaseous hydrogen and a metal salt. Such reactions occur in principle for solid carboxylic acids as well, but are slow if the solid acid remains dry. Even "insoluble" carboxylic acids may absorb enough water from the air and dissolve sufficiently in Orotic acid to corrode or dissolve iron, steel, and aluminum parts and containers. Carboxylic acids, like other acids, react with cyanide salts to generate gaseous hydrogen cyanide. The reaction is slower for dry, solid carboxylic acids. Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide. Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat. Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents. These reactions generate heat. A wide variety of products is possible. Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions.

Fire Hazard

Flash point data for Orotic acid are not available; however, Orotic acid is probably combustible.

Orotic acid Preparation Products And Raw materials

Raw materials

Preparation Products


Orotic acid Suppliers

Global( 259)Suppliers
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View Lastest Price from Orotic acid manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2019-04-22 Orotic acid
65-86-1
US $1.00 / g 1g 99% 5000 Kilogram/Kilograms per Month Cangzhou Wanyou New Material Technology Co.,Ltd
2018-12-16 Orotic acid
65-86-1
US $7.00 / kg 1kg 99% 100KG career henan chemical co

Orotic acid Spectrum


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