Editing Uracil

{{Short description|Chemical compound of RNA}}
{{Distinguish|uridine}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 418274850
| Name = Uracil 
| ImageFile = Uracil.svg
| ImageSize = 120px
| ImageClass = skin-invert-image
| ImageName = Structural formula of uracil
| ImageFileL1 = Uracil-3D-balls.png
| ImageNameL1 = Ball-and-stick model of uracil
| ImageFileR1 = Uracil-3D-vdW.png
| ImageNameR1 = Space-filling model of uracil
| PIN = Pyrimidine-2,4(1''H'',3''H'')-dione
| OtherNames = {{ubl|2-Oxy-4-oxypyrimidine|2,4(1''H'',3''H'')-Pyrimidinedione|2,4-Dihydroxypyrimidine|2,4-Pyrimidinediol}}
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4560
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 56HH86ZVCT
| SMILES = O=C1C=CNC(=O)N1
| SMILES_Comment = [[lactam]] form
| SMILES1 = Oc1nccc(O)n1
| SMILES1_Comment = [[lactim]] form
| CASNo = 66-22-8
| CASNo_Ref = {{cascite|correct|CAS}}
| ChEBI_Ref = {{ebicite|changed|EBI}} 
| ChEBI = 17568
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 566
| PubChem = 1174
| EC_number = 200-621-9
| DrugBank = DB03419
| KEGG = C00106
| 3DMet = B00026
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 1141
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8)
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = ISAKRJDGNUQOIC-UHFFFAOYSA-N
| RTECS = YQ8650000
| Beilstein = 606623 
| Gmelin = 2896
  }}
|Section2={{Chembox Properties
| Formula = C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O<sub>2</sub>
| MolarMass = 112.08676 g/mol
| Appearance = Solid
| Density = 1.32 g/cm<sup>3</sup>
| Solubility = Soluble
| MeltingPtC = 335
| MeltingPt_ref = <ref>{{cite book | vauthors = Myers RL |pages=92–93 | chapter = Chapter 29: Cytosine Thymine and Uracil | chapter-url=https://books.google.com/books?id=a4DuGVwyN6cC&q=Uracil+boiling+point&pg=PA92 |title=The 100 most important chemical compounds : a reference guide |date=2007 |publisher=Greenwood Press |location=Westport, Conn. |isbn=978-0-313-33758-1}}</ref>
| BoilingPt = N/A – decomposes
  }}
|Section7={{Chembox Hazards
| MainHazards = [[carcinogen]] and [[Birth defect|teratogen]] with chronic exposure
| NFPA-H = 1 
| NFPA-F = 1 
| NFPA-R =
| FlashPt = Non-flammable
| GHSPictograms = {{GHS07}}{{GHS08}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|315|319|335|361}}
| PPhrases = {{P-phrases|201|202|261|264|271|280|281|302+352|304+340|305+351+338|308+313|312|321|332+313|337+313|362|403+233|405|501}}
  }}
|Section8={{Chembox Related
| OtherCompounds = [[Thymine]] <br> [[Cytosine]]
  }}
}}
'''Uracil''' ({{IPAc-en|ˈ|j|ʊər|ə|s|ɪ|l}}) ([[nucleoside#List of nucleosides and corresponding nucleobases|symbol]] '''U''' or '''Ura''') is one of the four [[nucleotide base]]s in the [[nucleic acid]] [[RNA]]. The others are [[adenine]] (A), [[cytosine]] (C), and [[guanine]] (G). In RNA, uracil binds to [[adenine]] via two [[hydrogen bond]]s. In [[DNA]], the uracil nucleobase is replaced by [[thymine]] (T). Uracil is a [[demethylated]] form of [[thymine]].

Uracil is a common and naturally occurring [[pyrimidine]] derivative.<ref name="Garrett1">{{cite book |title=Principles of Biochemistry with a Human Focus|vauthors=Garrett RH, Grisham CM |publisher=Brooks/Cole Thomson Learning |year=1997 |location=United States}}</ref> The name "uracil" was coined in 1885 by the German chemist [[Robert Behrend]], who was attempting to synthesize derivatives of [[uric acid]].<ref>{{cite journal |vauthors=Behrend R |date=1885 |title=Versuche zur Synthese von Körpern der Harnsäurereihe |trans-title=Experiments on the synthesis of substances in the uric acid series |url=http://babel.hathitrust.org/cgi/pt?id=mdp.39015026321698;view=1up;seq=11 |journal=Annalen der Chemie |volume=229 |issue=1–2|pages=1–44 |doi=10.1002/jlac.18852290102 |quote=Dasselbe stellt sich sonach als Methylderivat der Verbindung: welche ich willkürlich mit dem Namen Uracil belege, dar. |trans-quote=The same compound is therefore represented as the methyl derivative of the compound, which I will arbitrarily endow with the name ‘''uracil''’.}}</ref> Originally discovered in 1900 by [[Alberto Ascoli]], it was isolated by [[hydrolysis]] of [[yeast]] [[nuclein]];<ref>{{cite journal|vauthors=Ascoli A|date=1900|title=Über ein neues Spaltungsprodukt des Hefenucleins|trans-title=On a new cleavage product of nucleic acid from yeast|url=https://books.google.com/books?id=SXtNAAAAYAAJ&pg=PA161|journal=Zeitschrift für Physiologische Chemie|volume=31|issue=1–2|pages=161–164|doi=10.1515/bchm2.1901.31.1-2.161|archive-url=https://web.archive.org/web/20180512002431/https://books.google.com/books?id=SXtNAAAAYAAJ&pg=PA161|archive-date=12 May 2018}}</ref> it was also found in [[bovine]] [[thymus]] and [[spleen]], [[herring]] [[sperm]], and [[wheat]] [[Cereal germ|germ]].<ref name="brown1"/> It is a planar, unsaturated compound that has the ability to absorb light.<ref name="Horton1"/>

Uracil that was formed extraterrestrially has been detected in the [[Murchison meteorite]],<ref name="Murch_base" /> in [[near-Earth asteroid]] [[162173 Ryugu|Ryugu]],<ref name="Oba 2023" /> and possibly on the surface of the moon [[Titan (moon)|Titan]].<ref name="Clark 2012"/> It has been synthesized under cold laboratory conditions similar to outer space, from pyrimidine embedded in water ice and exposed to ultraviolet light.<ref name="Nuevo 2009" />

==Properties==
In RNA, uracil [[base pair|base-pairs]] with adenine and replaces thymine during DNA transcription. [[Methylation]] of uracil produces thymine.<ref name="madsci1">{{cite web|url=http://www.madsci.org|title=MadSciNet: The 24-hour exploding laboratory|website=www.madsci.org|url-status=live|archive-url=https://web.archive.org/web/20050718075407/http://www.madsci.org/|archive-date=18 July 2005}}</ref> In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability and improved the efficiency of [[DNA replication]] (discussed below). Uracil pairs with adenine through [[hydrogen bonding]]. When [[base pairing]] with adenine, uracil acts as both a [[hydrogen bond]] acceptor and a hydrogen bond donor. In RNA, uracil binds with a [[ribose]] sugar to form the [[ribonucleoside]] [[uridine]]. When a [[phosphate]] attaches to uridine, uridine 5′-monophosphate is produced.<ref name="Horton1">{{cite book|title=Principles of Biochemistry|vauthors=Horton HR, Moran LA, Ochs RS, Rawn DJ, Scrimgeour KG|publisher=Prentice Hall|year=2002|isbn=9780130266729|edition=3rd|location=Upper Saddle River, NJ}}</ref>

Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the molecule may have from the lack of formal [[aromaticity]] is compensated by the cyclic-amidic stability.<ref name="brown1"/> The amide [[tautomer]] is referred to as the [[lactam]] structure, while the imidic acid tautomer is referred to as the [[lactim]] structure. These tautomeric forms are predominant at [[pH]]&nbsp;7. The lactam structure is the most common form of uracil.

:[[Image:Uracil tautomers.png|left|thumb|Uracil [[tautomers]]: [[Amide]] or [[lactam]] structure (left) and [[imide]] or [[lactim]] structure (right)]]{{clear left}}

Uracil also recycles itself to form nucleotides by undergoing a series of phosphoribosyltransferase reactions.<ref name="Garrett1"/> Degradation of uracil produces the substrates [[β-alanine]], [[carbon dioxide]], and [[ammonia]].<ref name = "Garrett1"/>

:{{chem2|C4H4N2O2}}→ {{chem2|H3NCH2CH2COO-}} + {{chem2|NH4+}} + {{chem2|CO2}}

Oxidative degradation of uracil produces urea and maleic acid in the presence of [[hydrogen peroxide|H<sub>2</sub>O<sub>2</sub>]] and [[Iron|Fe]]<sup>2+</sup> or in the presence of diatomic [[oxygen]] and Fe<sup>2+</sup>.

Uracil is a [[weak acid]]. The first site of [[ionization]] of uracil is not known.<ref name="Zorbach1">{{cite book|title=Synthetic Procedures in Nucleic Acid Chemistry: Physical and physicochemical aids in determination of structure|vauthors=Zorbach WW, Tipson RS|publisher=Wiley-Interscience|year=1973|isbn=9780471984184|volume=2|location=New York, NY}}</ref> The negative charge is placed on the oxygen anion and produces a [[Acid dissociation constant|p''K''<sub>a</sub>]] of less than or equal to 12. The basic p''K''<sub>a</sub>&nbsp;=&nbsp;−3.4, while the acidic p''K''<sub>a</sub>&nbsp;=&nbsp;9.38<sub>9</sub>. In the gas phase, uracil has four sites that are more acidic than water.<ref name="Lee1">{{cite journal | vauthors = Kurinovich MA, Lee JK | title = The acidity of uracil and uracil analogs in the gas phase: four surprisingly acidic sites and biological implications | journal = Journal of the American Society for Mass Spectrometry | volume = 13 | issue = 8 | pages = 985–995 | date = August 2002 | pmid = 12216739 | doi = 10.1016/S1044-0305(02)00410-5 | doi-access = free | bibcode = 2002JASMS..13..985K }}</ref>

===In DNA===
Uracil is rarely found in DNA, and this may have been an evolutionary change to increase genetic stability. This is because cytosine can deaminate spontaneously to produce uracil through hydrolytic deamination. Therefore, if there were an organism that used uracil in its DNA, the deamination of cytosine (which undergoes base pairing with guanine) would lead to formation of uracil (which would base pair with adenine) during DNA synthesis.
[[Uracil-DNA glycosylase]] excises uracil bases from double-stranded DNA. This enzyme would therefore recognize and cut out both types of uracil – the one incorporated naturally, and the one formed due to cytosine deamination, which would trigger unnecessary and inappropriate repair processes.<ref>{{Cite journal|vauthors=Békési A, Vértessy BG|date=2011|title=Uracil in DNA: error or signal?|url=https://www.scienceinschool.org/2011/issue18/uracil|journal=Science in School|pages=18|archive-url=https://web.archive.org/web/20160323021752/http://www.scienceinschool.org/2011/issue18/uracil|archive-date=23 March 2016}}</ref>

This problem is believed to have been solved in terms of evolution, that is by "tagging" (methylating) uracil. Methylated uracil is identical to thymine. Hence the hypothesis that, over time, thymine became standard in DNA instead of uracil. So cells continue to use uracil in RNA, and not in DNA, because RNA is shorter-lived than DNA, and any potential uracil-related errors do not lead to lasting damage. Apparently, either there was no evolutionary pressure to replace uracil in RNA with the more complex thymine, or uracil has some chemical property that is useful in RNA, which thymine lacks. Uracil-containing DNA still exists, for example in: 
* DNA of several [[phage]]s<ref>{{cite journal | vauthors = Wang Z, Mosbaugh DW | title = Uracil-DNA glycosylase inhibitor of bacteriophage PBS2: cloning and effects of expression of the inhibitor gene in Escherichia coli | journal = Journal of Bacteriology | volume = 170 | issue = 3 | pages = 1082–1091 | date = March 1988 | pmid = 2963806 | pmc = 210877 | doi = 10.1128/JB.170.3.1082-1091.1988 }}</ref>
* [[Endopterygote]] development
* Hypermutations during the synthesis of vertebrate antibodies.{{citation needed|date=December 2018}}

==Synthesis==

===Biological===
{{See also|Pyrimidine metabolism}}
Organisms synthesize uracil, in the form of [[uridine monophosphate]] (UMP), by decarboxylating [[orotidine 5'-monophosphate]] (orotidylic acid). In humans this decarboxylation is achieved by the enzyme [[Uridine monophosphate synthase|UMP synthase]]. In contrast to the purine nucleotides, the pyrimidine ring (orotidylic acid) that leads uracil is synthesized first and then linked to [[ribose phosphate]], forming UMP.<ref name="Loffler 2004">{{cite book | last1=Löffler | first1=Monika | last2=Zameitat | first2=Elke | title=Encyclopedia of Biological Chemistry | chapter=Pyrimidine Biosynthesis | publisher=Elsevier | year=2004 | doi=10.1016/b0-12-443710-9/00574-3 | pages=600–605| isbn=9780124437104 }}</ref>

===Laboratory===
There are many laboratory [[Chemical synthesis|synthesis]] of uracil available. The first reaction is the simplest of the syntheses, by adding water to [[cytosine]] to produce uracil and [[ammonia]]:<ref name = "Garrett1"/>
:{{chem2|C4H5N3O}} + {{chem2|H2O}} → {{chem2|C4H4N2O2}} + {{chem2|NH3}}

The most common way to synthesize uracil is by the [[condensation]] of [[malic acid]] with urea in [[fuming sulfuric acid]]:<ref name="brown1"/>

:{{chem2|C4H4O4}} + {{chem2|NH2CONH2}} → {{chem2|C4H4N2O2}} + 2 {{chem2|H2O}} + {{chem2|CO}}

Uracil can also be synthesized by a double decomposition of [[2-Thiouracil|thiouracil]] in aqueous [[chloroacetic acid]].<ref name="brown1"/>

[[Photodehydrogenation]] of 5,6-diuracil, which is synthesized by beta-[[alanine]] reacting with [[urea]], produces uracil.<ref name="Chittenden1">{{cite journal | vauthors = Chittenden GJ, Schwartz AW | title = Possible pathway for prebiotic uracil synthesis by photodehydrogenation | journal = Nature | volume = 263 | issue = 5575 | pages = 350–351 | date = September 1976 | pmid = 958495 | doi = 10.1038/263350a0 | s2cid = 4166393 | bibcode = 1976Natur.263..350C }}</ref>

===Prebiotic===
In 2009, [[NASA]] scientists reported having produced uracil from [[pyrimidine]] and water ice by exposing it to [[ultraviolet light]] under space-like conditions.<ref name="Nuevo 2009">{{cite journal | last1=Nuevo | first1=Michel | last2=Milam | first2=Stefanie N. | last3=Sandford | first3=Scott A. | last4=Elsila | first4=Jamie E. | last5=Dworkin | first5=Jason P. | title=Formation of Uracil from the Ultraviolet Photo-Irradiation of Pyrimidine in Pure H2O Ices | journal=Astrobiology | volume=9 | issue=7 | year=2009 | issn=1531-1074 | doi=10.1089/ast.2008.0324 | pages=683–695| pmid=19778279 | bibcode=2009AsBio...9..683N }}</ref> This suggests a possible natural original source for uracil.<ref name="NASA-20091105">{{cite news| vauthors = Marlaire R |url= http://www.nasa.gov/centers/ames/news/features/2009/urasil.html |title=NASA reproduces a building block of life in laboratory|date=5 November 2009 |access-date=5 March 2015|url-status=live |archive-url=https://web.archive.org/web/20160304234115/http://www.nasa.gov/centers/ames/news/features/2009/urasil.html |archive-date=4 March 2016 |publisher=[[NASA]] }}</ref> In 2014, NASA scientists reported that additional complex [[DNA]] and [[RNA]] [[organic compound]]s of [[life]], including uracil, [[cytosine]] and [[thymine]], have been formed in the laboratory under [[outer space]] conditions, starting with ice, [[pyrimidine]], ammonia, and methanol, which are compounds found in astrophysical environments.<ref name="Nuevo 2014">{{cite journal | last1=Nuevo | first1=Michel | last2=Materese | first2=Christopher K. | last3=Sandford | first3=Scott A. | title=The Photochemistry of Pyrimidine in Realistic Astrophysical ICES and the Production of Nucleobases | journal=The Astrophysical Journal | volume=793 | issue=2 | date=2014| issn=1538-4357 | doi=10.1088/0004-637x/793/2/125 | page=125| bibcode=2014ApJ...793..125N | s2cid=54189201 }}</ref> Pyrimidine, like [[polycyclic aromatic hydrocarbons]] (PAHs), a carbon-rich chemical found in the [[Universe]], may have been formed in [[red giant]]s or in [[Cosmic dust|interstellar dust]] and gas clouds.<ref name="NASA-20150303">{{cite news| vauthors = Marlaire R |url= http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory|title=NASA Ames reproduces the building blocks of life in laboratory|date=3 Mar 2015|access-date=5 Mar 2015|url-status=live|archive-url=https://web.archive.org/web/20150305083306/http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory/|archive-date=5 March 2015|publisher=[[NASA]]}}</ref>

Based on <sup>12</sup>C/<sup>13</sup>C [[isotopic ratio]]s of [[organic compounds]] found in the [[Murchison meteorite]], it is believed that uracil, [[xanthine]], and related molecules can also be formed extraterrestrially.<ref name="Murch_base">{{cite journal|display-authors=6|vauthors=Martins Z, Botta O, Fogel ML, Sephton MA, Glavin DP, Watson JS, Dworkin JP, Schwartz AW, Ehrenfreund P|date=2008|title=Extraterrestrial nucleobases in the Murchison meteorite|journal=[[Earth and Planetary Science Letters]]|volume=270|issue=1–2|pages=130–136|arxiv=0806.2286|bibcode=2008E&PSL.270..130M|doi=10.1016/j.epsl.2008.03.026|s2cid=14309508}}</ref>  Data from the [[Cassini mission]], orbiting in the [[Saturn]] system, suggests that uracil is present in the surface of the moon [[Titan (moon)|Titan]].<ref name="Clark 2012">{{cite journal|display-authors=6|vauthors=Clark RN, Pearson N, Brown RH, Cruikshank DP, Barnes J, Jaumann R, Soderblom L, Griffith C, Rannou P, Rodriguez S, Le Mouelic S, Lunine J, Sotin C, Baines KH, Buratti BJ, Nicholson PD, Nelson RM, Stephan K|date=2012|title=The Surface Composition of Titan|journal=American Astronomical Society|volume=44|pages=201.02|bibcode=2012DPS....4420102C}}</ref>  In 2023, uracil was observed in a sample from [[162173 Ryugu]], a [[near-Earth asteroid]], with no exposure to Earth's biosphere, giving further evidence for synthesis in space.<ref name="Oba 2023">{{cite journal | vauthors = Oba Y, Koga T, Takano Y, Ogawa NO, Ohkouchi N, Sasaki K, Sato H, Glavin DP, Dworkin JP, Naraoka H, Tachibana S, Yurimoto H, Nakamura T, Noguchi T, Okazaki R, Yabuta H, Sakamoto K, Yada T, Nishimura M, Nakato A, Miyazaki A, Yogata K, Abe M, Okada T, Usui T, Yoshikawa M, Saiki T, Tanaka S, Terui F, Nakazawa S, Watanabe SI, Tsuda Y | display-authors = 6 | title = Uracil in the carbonaceous asteroid (162173) Ryugu | journal = Nature Communications | volume = 14 | issue = 1 | pages = 1292 | date = 2023 | pmid = 36944653 | pmc = 10030641 | doi = 10.1038/s41467-023-36904-3 | bibcode = 2023NatCo..14.1292O }}</ref>

==Reactions==
[[Image:Uridin.svg|thumb|100px|Chemical structure of uridine]]
Uracil readily undergoes regular reactions including [[oxidation]], [[nitration]], and [[alkylation]]. While in the presence of [[phenol]] (PhOH) and [[sodium hypochlorite]] (NaOCl), uracil can be visualized in [[ultraviolet light]].<ref name="brown1">{{cite book|url=https://books.google.com/books?id=YpohAQAAMAAJ&q=malic+uracil|title=The Pyrimidines|vauthors=Brown DJ, Evans RF, Cowden WB, Fenn MD|publisher=Wiley|year=1994|isbn=9780471506560|veditors=Taylor EC|series=Heterocyclic Compounds|volume=52|location=New York, NY|archive-url=https://web.archive.org/web/20180512002431/https://books.google.com/books?id=YpohAQAAMAAJ&focus=searchwithinvolume&q=malic+uracil|archive-date=12 May 2018|url-status=live}}</ref> Uracil also has the capability to react with elemental [[halogen]]s because of the presence of more than one strongly electron donating group.<ref name="brown1"/>

Uracil readily undergoes addition to [[ribose]] [[sugar]]s and [[phosphate]]s to partake in synthesis and further reactions in the body.  Uracil becomes [[uridine]], [[uridine monophosphate]] (UMP), [[uridine diphosphate]] (UDP), [[uridine triphosphate]] (UTP), and [[uridine diphosphate glucose]] (UDP-glucose). Each one of these molecules is synthesized in the body and has specific functions.

When uracil reacts with anhydrous [[hydrazine]], a first-order kinetic reaction occurs and the uracil ring opens up.<ref name="Kochetkov1"/> If the [[pH]] of the reaction increases to >&nbsp;10.5, the uracil anion forms, making the reaction go much more slowly. The same slowing of the reaction occurs if the pH decreases, because of the protonation of the hydrazine.<ref name="Kochetkov1"/> The reactivity of uracil remains unchanged, even if the temperature changes.<ref name="Kochetkov1">{{cite book |title=Organic Chemistry of Nucleic Acids |publisher=Plenum Press |year=1972 |isbn=9781468429756 |volume=Part B |location=New York |doi=10.1007/978-1-4684-2973-2| veditors = Kochetkov NK, Budovskii EI }}</ref>

==Uses==
Uracil's use in the body is to help carry out the synthesis of many enzymes necessary for cell function through bonding with riboses and phosphates.<ref name="Garrett1"/> Uracil serves as [[allosteric]] regulator and [[coenzyme]] for reactions in animals and in plants.<ref name = "Brown2"/> UMP controls the activity of [[carbamoyl phosphate synthetase]] and [[aspartate transcarbamoylase]] in plants, while UDP and UTP regulate [[CPSase II]] activity in [[animal]]s. UDP-glucose regulates the conversion of [[glucose]] to [[galactose]] in the [[liver]] and other tissues in the process of [[carbohydrate metabolism]].<ref name="Brown2"/> Uracil is also involved in the [[biosynthesis]] of [[polysaccharides]] and the transportation of sugars containing [[aldehydes]].<ref name="Brown2">{{cite book|title=Ring Nitrogen and Key Biomolecules: The biochemistry of ''N''-heterocycles|publisher=Lluwer Academic Publishers|year=1998|isbn=9780412835704|veditors=Brown EG|location=Boston, MA|doi=10.1007/978-94-011-4906-8| vauthors = Brown EG |s2cid=9708198}}</ref> Uracil is important for the detoxification of many [[carcinogen]]s, for instance those found in tobacco smoke.<ref name="Olson">{{cite journal | vauthors = Olson KC, Sun D, Chen G, Sharma AK, Amin S, Ropson IJ, Spratt TE, Lazarus P | display-authors = 6 | title = Characterization of dibenzo[a,l]pyrene-trans-11,12-diol (dibenzo[def,p]chrysene) glucuronidation by UDP-glucuronosyltransferases | journal = Chemical Research in Toxicology | volume = 24 | issue = 9 | pages = 1549–1559 | date = September 2011 | pmid = 21780761 | pmc = 3177992 | doi = 10.1021/tx200178v }}</ref> Uracil is also required to detoxify many drugs such as cannabinoids (THC)<ref name="Mazur">{{cite journal | vauthors = Mazur A, Lichti CF, Prather PL, Zielinska AK, Bratton SM, Gallus-Zawada A, Finel M, Miller GP, Radomińska-Pandya A, Moran JH | display-authors = 6 | title = Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids | journal = Drug Metabolism and Disposition | volume = 37 | issue = 7 | pages = 1496–1504 | date = July 2009 | pmid = 19339377 | pmc = 2698943 | doi = 10.1124/dmd.109.026898 }}</ref> and morphine (opioids).<ref name="DeGregori">{{cite journal | vauthors = De Gregori S, De Gregori M, Ranzani GN, Allegri M, Minella C, Regazzi M | title = Morphine metabolism, transport and brain disposition | journal = Metabolic Brain Disease | volume = 27 | issue = 1 | pages = 1–5 | date = March 2012 | pmid = 22193538 | pmc = 3276770 | doi = 10.1007/s11011-011-9274-6 }}</ref> It can also slightly increase the risk for cancer in unusual cases in which the body is extremely deficient in [[folate]].<ref name = "Mashiyama1"/> The deficiency in folate leads to increased ratio of [[deoxyuridine monophosphate]]s (dUMP)/[[deoxythymidine monophosphate]]s (dTMP) and uracil misincorporation into DNA and eventually low production of DNA.<ref name="Mashiyama1">{{cite journal | vauthors = Mashiyama ST, Courtemanche C, Elson-Schwab I, Crott J, Lee BL, Ong CN, Fenech M, Ames BN | display-authors = 6 | title = Uracil in DNA, determined by an improved assay, is increased when deoxynucleosides are added to folate-deficient cultured human lymphocytes | journal = Analytical Biochemistry | volume = 330 | issue = 1 | pages = 58–69 | date = July 2004 | pmid = 15183762 | doi = 10.1016/j.ab.2004.03.065 }}</ref>

Uracil can be used for [[drug delivery]] and as a [[pharmaceutical]]. When elemental [[fluorine]] reacts with uracil, they produce [[5-fluorouracil]]. 5-Fluorouracil is an anticancer drug ([[antimetabolite]]) used to masquerade as uracil during the nucleic acid replication process.<ref name="Garrett1"/> Because 5-fluorouracil is similar in shape to, but does not undergo the same chemistry as, uracil, the drug inhibits [[RNA]] transcription enzymes, thereby blocking RNA synthesis and stopping the growth of cancerous cells.<ref name="Garrett1"/> Uracil can also be used in the synthesis of caffeine.<ref>{{cite journal|vauthors=Zajac MA, Zakrzewski AG, Kowal MG, Narayan S|date=2003|title=A novel method of caffeine synthesis from uracil|journal=Synthetic Communications|volume=33|issue=19|pages=3291–3297|doi=10.1081/SCC-120023986|s2cid=43220488}}</ref> Uracil has also shown potential as a HIV viral capsid inhibitor.<ref>{{cite journal | vauthors = Ramesh D, Mohanty AK, De A, Vijayakumar BG, Sethumadhavan A, Muthuvel SK, Mani M, Kannan T | display-authors = 6 | title = Uracil derivatives as HIV-1 capsid protein inhibitors: design, ''in silico'', ''in vitro'' and cytotoxicity studies | journal = RSC Advances | volume = 12 | issue = 27 | pages = 17466–17480 | date = June 2022 | pmid = 35765450 | pmc = 9190787 | doi = 10.1039/D2RA02450K | bibcode = 2022RSCAd..1217466R }}</ref> Uracil derivatives have antiviral, anti-tubercular and anti-leishmanial activity.<ref>{{Cite journal |last1=Ramesh |first1=Deepthi |last2=Vijayakumar |first2=Balaji Gowrivel |last3=Kannan |first3=Tharanikkarasu |date=2021-05-06 |title=Advances in Nucleoside and Nucleotide Analogues in Tackling Human Immunodeficiency Virus and Hepatitis Virus Infections |url=https://onlinelibrary.wiley.com/doi/10.1002/cmdc.202000849 |journal=ChemMedChem |language=en |volume=16 |issue=9 |pages=1403–1419 |doi=10.1002/cmdc.202000849 |pmid=33427377 |s2cid=231576801 |issn=1860-7179}}</ref><ref>{{Cite journal |last1=Ramesh |first1=Deepthi |last2=Vijayakumar |first2=Balaji Gowrivel |last3=Kannan |first3=Tharanikkarasu |date=2020-12-01 |title=Therapeutic potential of uracil and its derivatives in countering pathogenic and physiological disorders |url=https://www.sciencedirect.com/science/article/pii/S022352342030773X |journal=European Journal of Medicinal Chemistry |language=en |volume=207 |pages=112801 |doi=10.1016/j.ejmech.2020.112801 |pmid=32927231 |s2cid=221724578 |issn=0223-5234}}</ref><ref>{{cite journal | vauthors = Ramesh D, Sarkar D, Joji A, Singh M, Mohanty AK, G Vijayakumar B, Chatterjee M, Sriram D, Muthuvel SK, Kannan T | display-authors = 6 | title = First-in-class pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones against leishmaniasis and tuberculosis: Rationale, in vitro, ex vivo studies and mechanistic insights | journal = Archiv der Pharmazie | volume = 355 | issue = 4 | pages = e2100440 | date = April 2022 | pmid = 35106845 | doi = 10.1002/ardp.202100440 | s2cid = 246474821 }}</ref>

Uracil can be used to determine [[microbial]] contamination of [[tomato]]es. The presence of uracil indicates [[lactic acid]] [[bacteria]] contamination of the fruit.<ref>{{cite journal | vauthors = Hidalgo A, Pompei C, Galli A, Cazzola S | title = Uracil as an index of lactic acid bacteria contamination of tomato products | journal = Journal of Agricultural and Food Chemistry | volume = 53 | issue = 2 | pages = 349–355 | date = January 2005 | pmid = 15656671 | doi = 10.1021/jf0486489 | bibcode = 2005JAFC...53..349H }}</ref> Uracil derivatives containing a [[diazine]] ring are used in [[pesticide]]s.<ref name = "Pozharskii1"/> Uracil derivatives are more often used as [[antiphotosynthesis|antiphotosynthetic]] [[herbicide]]s, destroying weeds in [[cotton]], [[sugar beet]], [[turnip]]s, [[soybean|soya]], [[pea]]s, [[sunflower]] crops, [[vineyard]]s, [[berry]] plantations, and [[orchard]]s.<ref name="Pozharskii1">{{cite book|title=Heterocycles in Life and Society: An introduction to heterocyclic chemistry and biochemistry and the role of heterocycles in science, technology, medicine, and agriculture|vauthors=Pozharskii AF, Soldatenkov AT, Katritzky AR|publisher=John Wiley and Sons|year=1997|isbn=9780471960348|location=New York, NY}}</ref> Uracil derivatives can enhance the activity of antimicrobial [[Polysaccharide|polysaccharides]] such as [[chitosan]].<ref>{{Cite journal |last1=Vijayakumar |first1=Balaji Gowrivel |last2=Ramesh |first2=Deepthi |last3=Manikandan |first3=K. Santhosh |last4=Theresa |first4=Mary |last5=Sethumadhavan |first5=Aiswarya |last6=Priyadarisini |first6=V. Brindha |last7=Radhakrishnan |first7=E. K. |last8=Mani |first8=Maheswaran |last9=Kannan |first9=Tharanikkarasu |date=2022-06-01 |title=Chitosan with pendant (E)-5-((4-acetylphenyl)diazenyl)-6-aminouracil groups as synergetic antimicrobial agents |url=https://pubs.rsc.org/en/content/articlelanding/2022/tb/d2tb00240j |journal=Journal of Materials Chemistry B |language=en |volume=10 |issue=21 |pages=4048–4058 |doi=10.1039/D2TB00240J |pmid=35507973 |s2cid=248526212 |issn=2050-7518}}</ref>

In [[yeast]], uracil concentrations are inversely proportional to uracil permease.<ref>{{cite journal | vauthors = Séron K, Blondel MO, Haguenauer-Tsapis R, Volland C | title = Uracil-induced down-regulation of the yeast uracil permease | journal = Journal of Bacteriology | volume = 181 | issue = 6 | pages = 1793–1800 | date = March 1999 | pmid = 10074071 | pmc = 93577 | doi = 10.1128/JB.181.6.1793-1800.1999 }}</ref>

Mixtures containing uracil are also commonly used to test [[Reversed-phase chromatography|reversed-phase]] [[High-performance liquid chromatography|HPLC]] columns. As uracil is essentially unretained by the non-polar stationary phase, this can be used to determine the dwell time (and subsequently dwell volume, given a known flow rate) of the system.

== References ==
{{Reflist}}

== External links ==
* [http://gmd.mpimp-golm.mpg.de/Spectrums/b3fbd853-fbf6-4ae3-aab2-e2fb5b212be3.aspx Uracil MS Spectrum]

{{Nucleobases, nucleosides, and nucleotides}}
{{Purinergics}}
{{Authority control}}

[[Category:Nucleobases]]
[[Category:Pyrimidinediones]]