Uracil 39354 219917495 2008-06-17T13:18:04Z 141.85.0.101 {{Chembox new | Name = Uracil | ImageFile = Uracil chemical structure.png | ImageSize=120px | IUPACName = Pyrimidine-2,4(1''H'',3''H'')-dione | OtherNames = Uracil, 2-oxy-4-oxy pyrimidine,<br/>2,4(1H,3H)-pyrimidinedione,<br/>2,4-dihydroxypryimidine,<br /> 2,4-pyrimidinediol | Section1 = {{Chembox Identifiers | SMILES = O=C1NC=CC(=O)N1 | CASNo = 66-22-8 | RTECS = YQ8650000 }} | 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 = | Solubility = Soluble | MeltingPt = 335 °C | BoilingPt = N/A }} | Section7 = {{Chembox Hazards | MainHazards = carcinogen & teratogen with chronic exposure | NFPA-H = 1 | NFPA-F = 1 | NFPA-R = | FlashPt = non flammable }} | Section8 = {{Chembox Related | OtherCpds = [[Thymine]] }} }} '''Uracil''' is a common and naturally occurring [[pyrimidine]] derivative.<ref name="Garrett1">Garrett, Reginald H.; Grisham, Charles M. Principals of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.</ref> Originally discovered in 1900, it was isolated by [[hydrolysis]] of [[yeast]] [[nuclein]] that was found in [[bovine]] [[thymus]] and [[spleen]], [[herring]], [[sperm]], and [[wheat]] [[germ]].<ref name="brown1">Brown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.</ref> It is a planar, unsaturated compound that has the ability to absorb light.<ref name="Horton1">Horton, Robert H.; ''et al.''Principles of Biochemistry. 3rd ed. Upper Saddle River, NJ: Prentice Hall, 2002.</ref> ==Properties== Found in [[RNA]], it [[base pair]]s with [[adenine]] and is replaced by [[thymine]] in [[DNA]]. Methylation of uracil produces [[thymine]].<ref name="madsci1">www.madsci.org</ref> It turns into thymine to protect the DNA and to improve the efficiency of [[DNA replication]]. Uracil can base pair with any of the bases depending on how the molecule arranges itself on the [[helix]], but readily pairs with [[adenine]] because the methyl group is repelled into a fixed position.<ref name="madsci1">www.madsci.org</ref> Uracil pairs with adenine through [[hydrogen bonding]]. Uracil is the [[hydrogen bond acceptor]] and can form two hydrogen bonds. Uracil can also bind with a [[ribose]] sugar to form a [[ribonucleoside]], [[uridine]]. When a [[phosphate]] attaches to uridine, uridine 5'-monophosphate is produced.<ref name="Horton1">Horton, Robert H.; ''et al.''Principles of Biochemistry. 3rd ed. Upper Saddle River, NJ: Prentice Hall, 2002.</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">Brown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.</ref> The keto [[tautomer]] is referred to the [[lactam]] structure, while the imidic acid tautomer is referred to as the [[lactim]] structure. These tautomeric forms are predominant at [[pH]]=7. The lactam structure is the most common form of uracil. :[[Image:Uracil tautomers.png|left|thumb|Uracil tautomers: Keto or lactam structure (left) and imidic or lactim structure (right)]]<br style="clear:left;"/> Uracil also recycles itself to form nucleotides by undergoing a series of [[phosphoribosyltransferase reaction]]s.<ref name="Garrett1">Garrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.</ref> Degradation of uracil produces substrates, [[aspartate]], [[carbon dioxide]], and [[ammonia]].<ref name="Garrett1">Garrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.</ref> :C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O<sub>2</sub> → H<sub>3</sub>NCH<sub>2</sub>CH<sub>2</sub>COO<sup>-</sup> + NH<sub>4</sub> + CO<sub>2</sub> Oxidative degradation of uracil produces urea and maleic acid in the presence of [[hydrogen peroxide|H<sub>2</sub>O<sub>2</sub>]] and [[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">Zorbach, W.W. Synthetic Procedures in Nucleic Acid Chemistry: Physical and Physicochemical Aids in Determination of Structure. Vol 2. New York: Wiley-Interscience, 1973.</ref> The negative charge is placed on the oxygen anion and produces a [[Acid dissociation constant|pK<sub>a</sub>]] of less than or equal to 12. The basic pK<sub>a</sub> = -3.4, while the acidic pK<sub>a</sub> = 9.38<sub>9</sup>. In the gas phase, uracil has 4 sites that are more acidic than water.<ref name="Lee1">Lee, J.K.; Kurinovich, Ma. ''J Am Soc Mass Spectrom.'''''13'''(8), 2005, 985-95.</ref> ==Synthesis== There are many laboratory [[Chemical synthesis|syntheses]] 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">Garrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.</ref> The most common way to synthesize uracil is by the [[condensation]] of [[malic acid]] with urea in [[fuming sulfuric acid]]<ref name="brown1">Brown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.</ref> as seen below also. Uracil can also be synthesized by a double decomposition of [[thiouracil]] in aqueous [[chloroacetic acid]].<ref name="brown1">Brown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.</ref> :C<sub>4</sub>H<sub>5</sub>N<sub>3</sub>O + H<sub>2</sub>O → C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O<sub>2</sub> + NH<sub>3</sub> :C<sub>4</sub>H<sub>4</sub>O<sub>4</sub> + CH<sub>4</sub>N<sub>2</sub>O → C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>O<sub>2</sub> + 2 H<sub>2</sub>O + CO [[Photodehydrogenation]] of 5,6-diuracil, which is synthesized by beta-[[alanine]] reacting with [[urea]], produces uracil.<ref name="Chittenden1">Chittenden, G.J.F.; Schwartz, Alan W. ''Nature.'''''263,'''(5575), 350-1.</ref><!-- Image with unknown copyright status removed:[[Image:reaction1a.gif]] --> ==Reactions== Uracil readily undergoes regular reactions including [[oxidation]], [[nitration]], and [[alkylation]]. While in the presence of [[phenol|PhOH]]/[[Sodium hypochlorite|NaOCl]], uracil can be visualized in the blue region of [[UV light]].<ref name="brown1">Brown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.</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">Brown, D.J. Heterocyclic COmpounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.</ref> <!--deleted image removed [[Image:bromorxn.gif]] --> 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 in synthesized in the body and has specific functions. :[[Image:U chemical structure.png|thumb|left|100px|Chemical structure of uridine]]<br style="clear:left;"/> When uracil reactes with anhydrous [[hydrazine]] a first order kinetic reaction occurs and the ring of uracil opens up.<ref name="Kochetkov1">Kochetkov, N.K. and Budovskii, E.I. Organic Chemistry of Nucleic Acids Part B. New York: Plenum Press, 1972.</ref> If the pH of the reaction increases to >10.5 the uracil anion forms making the reaction go much slower, the same slowing of the reaction occurs if the pH decreases because of the protonation of the hydrazine.<ref name="Kochetkov1">Kochetkov, N.K. and Budovskii, E.I. Organic Chemistry of Nucleic Acids Part B. New York: Plenum Press, 1972.</ref> The reactivity of uracil is unchanged even if the temperature changes.<ref name="Kochetkov1">Kochetkov, N.K. and Budovskii, E.I. Organic Chemistry of Nucleic Acids Part B. New York: Plenum Press, 1972.</ref> ==Uses== Uracil can be used for [[drug delivery]] and as a [[pharmaceutical]]. When elemental [[fluorine]] is reacted with uracil, [[5-fluorouracil]] is produced. 5-Fluorouracil is an anticancer drug ([[antimetabolite]]) used to [[masquerade]] as uracil during the nucleic acid replication process.<ref name="Garrett1">Garrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.</ref> Because 5-Fluorouracil is similar in shape to, but does not perform the same chemisty as uracil the drug inhibits [[RNA]] replication enzymes, thereby eliminating RNA synthesis and stopping the growth of cancerous cells.<ref name="Garrett1">Garrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.</ref> 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">Garrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.</ref> Uracil serves as [[allosteric]] regulator and [[coenzyme]] for reactions in the human body and in plants.<ref name="Brown2">Brown, E.G. Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles. Boston: Lluwer Academic Publishers, 1998.</ref> UMP controls the activity of [[carbamoyl phosphate synthetase]] and [[aspartate transcarbamoylase]] in plants, while UDP and UTP requlate [[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">Brown, E.G. Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles. Boston: Lluwer Academic Publishers, 1998.</ref> Uracil is also involved in the [[biosynthesis]] of [[polysaccharides]] and the transportation of sugars containing [[aldehydes]].<ref name="Brown2">Brown, E.G. Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles. Boston: Lluwer Academic Publishers, 1998.</ref> It can also increase the risk for cancer in cases where the body is extremely deficient in [[folate]].<ref name="Mashiyama1">Mashiyama, S.T; ''et al.''''Anal Biochem. '''''330'''(1),2004, 58-69.</ref> The deficiency in folate leads to increased ratio of [[deoxyuracilmonophosphates]] (dUMP)/[[deoxythyminemonophosphates]] (dTMP) and uracil misincorporation into DNA and eventually low production of DNA.<ref name="Mashiyama1">Mashiyama, S.T; ''et al.''''Anal Biochem. '''''330'''(1),2004, 58-69.</ref> Uracil can be used to determine [[microbial]] contamination of [[tomato]]es. The presence of uracil is an indication of [[lactic acid]] [[bacteria]] contamination in the fruit.<ref name="Hidalgo1">Hildalgo, A; ''et al.''''J Agric Food Chem.'''''53'''(2),2005, 349-55.</ref> Uracil derivatives containing a [[diazine]] ring are used in [[pesticides]].<ref name="Pozharskii1">Pozharskii, A.F.; ''et al.''Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry and Biochemistry and the Role of Heterocycles in Science, Technology, Medicine, and Agriculture. New York: John Wiley and Sons, 1997.</ref> Uracil derivatives are more often used as [[antiphotosynthesis|antiphotosynthetic]] herbicides, destroying weeds in [[cotton]], [[sugar beet]], [[turnips]], [[soybean|soya]], [[peas]], [[sunflower]] crops, [[vineyards]], [[berry]] plantations, and [[orchards]].<ref name="Pozharskii1">Pozharskii, A.F.; ''et al.''Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry and Biochemistry and the Role of Heterocycles in Science, Technology, Medicine, and Agriculture. New York: John Wiley and Sons, 1997.</ref> ==References== {{reflist|2}} {{Nucleobases, nucleosides, and nucleotides}} [[Category:Pyrimidines]] [[bg:Урацил]] [[ca:Uracil]] [[cs:Uracil]] [[da:Uracil]] [[de:Uracil]] [[es:Uracilo]] [[eo:Uracilo]] [[fr:Uracile]] [[gl:Uracilo]] [[id:Urasil]] [[it:Uracile]] [[he:אורציל]] [[lt:Uracilas]] [[hu:Uracil]] [[nl:Uracil]] [[ja:ウラシル]] [[no:Uracil]] [[pl:Uracyl]] [[pt:Uracilo]] [[ro:Uracil]] [[ru:Урацил]] [[simple:Uracil]] [[sl:Uracil]] [[sr:Урацил]] [[sh:Uracil]] [[fi:Urasiili]] [[sv:Uracil]] [[vi:Uracil]] [[tr:Urasil]] [[uk:Урацил]] [[zh:尿嘧啶]]