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| uracil |
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| CHEBI:17568 |
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| A common and naturally occurring pyrimidine nucleobase in which the pyrimidine ring is substituted with two oxo groups at positions 2 and 4. Found in RNA, it base pairs with adenine and replaces thymine during DNA transcription. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:46375, CHEBI:9882, CHEBI:15288, CHEBI:27210
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| ChemicalBook:CB7876938, ZINC000008551095 |
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Molfile
XML
SDF
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more structures >>
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| Uracil () (symbol U or Ura) is one of the four nucleotide bases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. 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. The name "uracil" was coined in 1885 by the German chemist Robert Behrend, who was attempting to synthesize derivatives of uric acid. Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein; it was also found in bovine thymus and spleen, herring sperm, and wheat germ. It is a planar, unsaturated compound that has the ability to absorb light.
Uracil that was formed extraterrestrially has been detected in the Murchison meteorite, in near-Earth asteroid Ryugu, and possibly on the surface of the moon Titan. It has been synthesized under cold laboratory conditions similar to outer space, from pyrimidine embedded in water ice and exposed to ultraviolet light. |
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Read full article at Wikipedia
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| InChI=1S/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8) |
| ISAKRJDGNUQOIC-UHFFFAOYSA-N |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Daphnia magna
(NCBI:txid35525)
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See:
Mixtures of similarly acting compounds in Daphnia magna: From gene to metabolite and beyondTine Vandenbrouck, Oliver A.H. Jones, Nathalie Dom, Julian L. Griffin, Wim De CoenEnvironment International 36 (2010) 254-268
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Saccharomyces cerevisiae
(NCBI:txid4932)
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Source: yeast.sf.net
See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Cordyceps sinensis
(NCBI:txid72228)
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Found in
mycelium
(BTO:0001436).
Ethanolic extract of dried mycelia
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
Saccharomyces cerevisiae metabolite
Any fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae ).
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
Daphnia magna metabolite
A Daphnia metabolite produced by the species Daphnia magna.
allergen
A chemical compound, or part thereof, which causes the onset of an allergic reaction by interacting with any of the molecular pathways involved in an allergy.
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prodrug
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
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View more via ChEBI Ontology
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Outgoing
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uracil
(CHEBI:17568)
has role
Daphnia magna metabolite
(CHEBI:83056)
uracil
(CHEBI:17568)
has role
Escherichia coli metabolite
(CHEBI:76971)
uracil
(CHEBI:17568)
has role
Saccharomyces cerevisiae metabolite
(CHEBI:75772)
uracil
(CHEBI:17568)
has role
allergen
(CHEBI:50904)
uracil
(CHEBI:17568)
has role
human metabolite
(CHEBI:77746)
uracil
(CHEBI:17568)
has role
mouse metabolite
(CHEBI:75771)
uracil
(CHEBI:17568)
has role
prodrug
(CHEBI:50266)
uracil
(CHEBI:17568)
is a
pyrimidine nucleobase
(CHEBI:26432)
uracil
(CHEBI:17568)
is a
pyrimidone
(CHEBI:38337)
uracil
(CHEBI:17568)
is tautomer of
(4S)-4-hydroxy-3,4-dihydropyrimidin-2(1H)-one
(CHEBI:43254)
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Incoming
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(5R)-6-hydroxy-5-[4-(2-hydroxyethyl)piperidin-1-yl]-5-phenyluracil
(CHEBI:40990)
has functional parent
uracil
(CHEBI:17568)
(Z)-2-methylureidoacrylic acid
(CHEBI:143867)
has functional parent
uracil
(CHEBI:17568)
({[(1R,2R)-2-(uracil-1-yl)cyclopentyl]oxy}methyl)phosphonic acid
(CHEBI:42248)
has functional parent
uracil
(CHEBI:17568)
1,3-dimethyluracil
(CHEBI:74763)
has functional parent
uracil
(CHEBI:17568)
1,5-dimethyluracil
(CHEBI:74765)
has functional parent
uracil
(CHEBI:17568)
1-(3-O-phosphono-β-D-arabinofuranosyl)uracil
(CHEBI:46271)
has functional parent
uracil
(CHEBI:17568)
1-(ethoxymethyl)-5-isopropyl-6-(phenylsulfanyl)uracil
(CHEBI:40152)
has functional parent
uracil
(CHEBI:17568)
1-[3-(4-carboxypiperidin-1-yl)-3-deoxy-β-D-arabinofuranosyl]pyrimidine-2,4(1H,3H)-dione
(CHEBI:44260)
has functional parent
uracil
(CHEBI:17568)
1-methyluracil
(CHEBI:69445)
has functional parent
uracil
(CHEBI:17568)
2'-deoxyuridine
(CHEBI:16450)
has functional parent
uracil
(CHEBI:17568)
3,5-dimethyluracil
(CHEBI:74766)
has functional parent
uracil
(CHEBI:17568)
3-(5-bromouracil-1-yl)-L-alanine
(CHEBI:47280)
has functional parent
uracil
(CHEBI:17568)
3-(5-fluorouracil-1-yl)-L-alanine
(CHEBI:42549)
has functional parent
uracil
(CHEBI:17568)
3-(5-iodouracil-1-yl)-L-alanine
(CHEBI:43500)
has functional parent
uracil
(CHEBI:17568)
3-(uracil-1-yl)-L-alanine
(CHEBI:15851)
has functional parent
uracil
(CHEBI:17568)
3-methyluracil
(CHEBI:74732)
has functional parent
uracil
(CHEBI:17568)
4-[(1E,7E)-8-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-3,6-dioxa-2,7-diazaocta-1,7-dien-1-yl]benzoic acid
(CHEBI:39893)
has functional parent
uracil
(CHEBI:17568)
4-thiouracil
(CHEBI:232485)
has functional parent
uracil
(CHEBI:17568)
5,6-dihydrouracil
(CHEBI:15901)
has functional parent
uracil
(CHEBI:17568)
5,6-dihydroxyuracil
(CHEBI:132197)
has functional parent
uracil
(CHEBI:17568)
5-(4,5-dihydroxypentyl)uracil
(CHEBI:132195)
has functional parent
uracil
(CHEBI:17568)
5-[3-(benzyloxy)benzyl]-6-hydroxy-1-[(2-hydroxyethoxy)methyl]pyrimidine-2,4(1H,3H)-dione
(CHEBI:40929)
has functional parent
uracil
(CHEBI:17568)
5-acetamido-6-formamido-3-methyluracil
(CHEBI:32643)
has functional parent
uracil
(CHEBI:17568)
5-benzyl-1-(2-hydroxyethoxymethyl)uracil
(CHEBI:41037)
has functional parent
uracil
(CHEBI:17568)
5-benzyloxybenzylacyclouridine
(CHEBI:39579)
has functional parent
uracil
(CHEBI:17568)
5-bromouracil
(CHEBI:20552)
has functional parent
uracil
(CHEBI:17568)
5-carboxy-2'-deoxyuridine
(CHEBI:102485)
has functional parent
uracil
(CHEBI:17568)
5-chloro-6-{[(2Z)-2-iminopyrrolidin-1-yl]methyl}uracil
(CHEBI:47334)
has functional parent
uracil
(CHEBI:17568)
5-chlorouracil
(CHEBI:60762)
has functional parent
uracil
(CHEBI:17568)
5-diazouracil
(CHEBI:34454)
has functional parent
uracil
(CHEBI:17568)
5-fluorouracil
(CHEBI:46345)
has functional parent
uracil
(CHEBI:17568)
5-hydroxymethyluracil
(CHEBI:16964)
has functional parent
uracil
(CHEBI:17568)
5-hydroxyuracil
(CHEBI:29115)
has functional parent
uracil
(CHEBI:17568)
5-iodouracil
(CHEBI:43636)
has functional parent
uracil
(CHEBI:17568)
5-nitrouracil
(CHEBI:60763)
has functional parent
uracil
(CHEBI:17568)
6-(3,5-dimethylbenzyl)-1-(ethoxymethyl)-5-isopropyluracil
(CHEBI:42702)
has functional parent
uracil
(CHEBI:17568)
6-[(1,2-dideoxy-D-ribityl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149751)
has functional parent
uracil
(CHEBI:17568)
6-[(1,3-dideoxy-D-ribityl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149756)
has functional parent
uracil
(CHEBI:17568)
6-[(1,4-dideoxy-D-ribityl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149744)
has functional parent
uracil
(CHEBI:17568)
6-[(1,5-dideoxy-D-ribityl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149720)
has functional parent
uracil
(CHEBI:17568)
6-[(1-deoxy-D-ribityl)methyl]-5-[(1E)-3-oxobut-1-en-1-yl]uracil
(CHEBI:149716)
has functional parent
uracil
(CHEBI:17568)
6-[(2-hydroxyethyl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149753)
has functional parent
uracil
(CHEBI:17568)
6-[(3-hydroxypropyl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149757)
has functional parent
uracil
(CHEBI:17568)
6-[(4-hydroxybutyl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149748)
has functional parent
uracil
(CHEBI:17568)
6-[(5-hydroxypentyl)amino]-5-[(E)-(2-oxopropylidene)amino]uracil
(CHEBI:149728)
has functional parent
uracil
(CHEBI:17568)
6-benzyl-1-(benzyloxymethyl)-5-isopropyluracil
(CHEBI:45910)
has functional parent
uracil
(CHEBI:17568)
6-cyclohexylsulfanyl-1-ethoxymethyl-5-isopropyluracil
(CHEBI:62748)
has functional parent
uracil
(CHEBI:17568)
6-methyl-5-[(1E)-3-oxobut-1-en-1-yl]uracil
(CHEBI:149702)
has functional parent
uracil
(CHEBI:17568)
6-methyluracil
(CHEBI:74733)
has functional parent
uracil
(CHEBI:17568)
6-propyl-2-thiouracil
(CHEBI:8502)
has functional parent
uracil
(CHEBI:17568)
aminouracil
(CHEBI:22532)
has functional parent
uracil
(CHEBI:17568)
butafenacil
(CHEBI:143863)
has functional parent
uracil
(CHEBI:17568)
dasabuvir
(CHEBI:85182)
has functional parent
uracil
(CHEBI:17568)
emivirine
(CHEBI:44143)
has functional parent
uracil
(CHEBI:17568)
orotate
(CHEBI:30839)
has functional parent
uracil
(CHEBI:17568)
orotic acid
(CHEBI:16742)
has functional parent
uracil
(CHEBI:17568)
saflufenacil
(CHEBI:142824)
has functional parent
uracil
(CHEBI:17568)
thiouracil
(CHEBI:348530)
has functional parent
uracil
(CHEBI:17568)
tipiracil
(CHEBI:90879)
has functional parent
uracil
(CHEBI:17568)
uracil-5-carboxylic acid
(CHEBI:17477)
has functional parent
uracil
(CHEBI:17568)
uracil-6-ylacetic acid
(CHEBI:46371)
has functional parent
uracil
(CHEBI:17568)
uridine
(CHEBI:16704)
has functional parent
uracil
(CHEBI:17568)
uridines
(CHEBI:27242)
has functional parent
uracil
(CHEBI:17568)
uracil-1-yl group
(CHEBI:30759)
is substituent group from
uracil
(CHEBI:17568)
(4S)-4-hydroxy-3,4-dihydropyrimidin-2(1H)-one
(CHEBI:43254)
is tautomer of
uracil
(CHEBI:17568)
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pyrimidine-2,4(1H,3H)-dione
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2,4(1H,3H)-pyrimidinedione
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NIST Chemistry WebBook
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2,4-Dioxopyrimidine
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HMDB
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2,4-Pyrimidinedione
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HMDB
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U
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ChEBI
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Ura
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CBN
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Uracil
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KEGG COMPOUND
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URACIL
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PDBeChem
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uracil
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UniProt
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Urazil
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ChEBI
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C00001513
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KNApSAcK
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C00106
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KEGG COMPOUND
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D00027
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KEGG DRUG
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DB03419
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DrugBank
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HMDB0000300
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HMDB
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URA
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PDBeChem
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Uracil
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Wikipedia
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URACIL
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MetaCyc
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| View more database links |
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2896
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Gmelin Registry Number
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Gmelin
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606623
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Reaxys Registry Number
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Reaxys
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66-22-8
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CAS Registry Number
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KEGG COMPOUND
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66-22-8
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CAS Registry Number
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ChemIDplus
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66-22-8
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CAS Registry Number
|
NIST Chemistry WebBook
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Papageorgiou AC, Fischer S, Reichert J, Diller K, Blobner F, Klappenberger F, Allegretti F, Seitsonen AP, Barth JV (2012)
Chemical transformations drive complex self-assembly of uracil on close-packed coinage metal surfaces.
ACS nano 6, 2477-2486 [PubMed:22356544]
[show Abstract]
We address the interplay of adsorption, chemical nature, and self-assembly of uracil on the Ag(111) and Cu(111) surfaces as a function of molecular coverage (0.3 to 1 monolayer) and temperature. We find that both metal surfaces act as templates and the Cu(111) surface acts additionally as a catalyst for the resulting self-assembled structures. With a combination of STM, synchrotron XPS, and NEXAFS studies, we unravel a distinct polymorphism on Cu(111), in stark contrast to what is observed for the case of uracil on the more inert Ag(111) surface. On Ag(111) uracil adsorbs flat and intact and forms close-packed two-dimensional islands. The self-assembly is driven by stable hydrogen-bonded dimers with poor two-dimensional order. On Cu(111) complex structures are observed exhibiting, in addition, a strong annealing temperature dependence. We determine the corresponding structural transformations to be driven by gradual deprotonation of the uracil molecules. Our XPS study reveals unambiguously the tautomeric signature of uracil in the contact layer and on Cu(111) the molecule's deprotonation sites. The metal-mediated deprotonation of uracil and the subsequent electron localization in the molecule determine important biological reactions. Our data show a dependence between molecular coverage and molecule-metal interaction on Cu(111), as the molecules tilt at higher coverages in order to accommodate a higher packing density. After deprotonation of both uracil N atoms, we observe an adsorption geometry that can be understood as coordinative anchoring with a significant charge redistribution in the molecule. DFT calculations are employed to analyze the surface bonding and accurately describe the pertaining electronic structure. | Rapoport VL, Malkin VM, Savina AV, Safargaleeva EA, Goriuchko VV (2012)
[Luminescence of stable stacking aggregates of adenine and uracil in water].
Biofizika 57, 14-20 [PubMed:22567906]
[show Abstract]
Luminescence and excitation spectra of the highly luminescent stacking dimers of adenine and uracil in water solutions are studied. By the luminescence excitation spectra method it is shown that the stacking aggregates of adenine and uracil are formed with participation of rare forms of monomer molecules: N7H tautomers of adenine and the uracil molecules in rare forms of hydratation, for example molecules without H-bonds with water. The study of temperature dependence of luminescence intensity of monomers and stacking dimers of uracil has shown that stacking dimers do not dissociate even at 85 degrees C similarly as described earlier for adenine and adenosine. Stable stacking aggregates of nucleic bases are most likely to be the precursors of RNA molecules in chemical evolution. This hypothesis is supported by new data on their stability. | Wettergren Y, Carlsson G, Odin E, Gustavsson B (2012)
Pretherapeutic uracil and dihydrouracil levels of colorectal cancer patients are associated with sex and toxic side effects during adjuvant 5-fluorouracil-based chemotherapy.
Cancer 118, 2935-2943 [PubMed:22020693]
[show Abstract]
BackgroundIn Nordic countries, the standard treatment of colorectal cancer (CRC) in the adjuvant setting is bolus 5-fluorouracil (5-FU) plus leucovorin alone or in combination with oxaliplatin. 5-FU competes with the natural occurring pyrimidine uracil (Ura) as a substrate for dihydropyrimidine dehydrogenase (DPD; enzyme commission number 1.3.1.2). Low DPD activity is associated with toxicity during treatment. Pretherapeutic detection of DPD deficiency could prevent severe toxicity otherwise limiting drug administration. Assays showing that DPD deficiency impairs breakdown of Ura to dihydrouracil (UH(2)) seem promising for clinical use.MethodsUrine was collected from 56 untreated volunteers and 143 patients with CRC before adjuvant treatment. Ura and UH(2) were analyzed using a column-switching high-performance liquid chromatography method that incorporates reversed-phase and cation-exchange columns. Ura, UH(2), and UH(2)/Ura levels were related to toxicity.ResultsUra and UH(2) in patients were not different from controls. UH(2) was significantly higher in women compared with men. The UH(2)/Ura ratio, however, did not differ according to sex. Low UH(2) and UH(2)/Ura levels were associated with diarrhea in men. Women experiencing thrombocytopenia had significantly higher Ura compared with women with no thrombocytopenia. The UH(2)/Ura ratio correlated negatively with total toxicity score in men (r = -0.39, P = .020).ConclusionPretherapeutic Ura and UH(2) levels per se may be related to risk of side effects during adjuvant 5-FU-based treatment, whereas the UH(2)/Ura ratio may not always reveal such a risk. Sex is a strong risk factor for toxicity, showing the importance of evaluating male and female patients separately. | Bulgar AD, Weeks LD, Miao Y, Yang S, Xu Y, Guo C, Markowitz S, Oleinick N, Gerson SL, Liu L (2012)
Removal of uracil by uracil DNA glycosylase limits pemetrexed cytotoxicity: overriding the limit with methoxyamine to inhibit base excision repair.
Cell death & disease 3, e252 [PubMed:22237209]
[show Abstract]
Uracil DNA glycosylase (UDG) specifically removes uracil bases from DNA, and its repair activity determines the sensitivity of the cell to anticancer agents that are capable of introducing uracil into DNA. In the present study, the participation of UDG in the response to pemetrexed-induced incorporation of uracil into DNA was studied using isogenic human tumor cell lines with or without UDG (UDG(+/+)/UDG(-/-)). UDG(-/-) cells were very sensitive to pemetrexed. Cell killing by pemetrexed was associated with genomic uracil accumulation, stalled DNA replication, and catastrophic DNA strand breaks. By contrast, UDG(+/+) cells were >10 times more resistant to pemetrexed due to the rapid removal of uracil from DNA by UDG and subsequent repair of the resultant AP sites (abasic sites) via the base excision repair (BER). The resistance to pemetrexed in UDG(+/+) cells could be reversed by the addition of methoxyamine (MX), which binds to AP sites and interrupts BER pathway. Furthermore, MX-bound AP sites induced cell death was related to their cytotoxic effect of dual inactivation of UDG and topoisomerase IIα, two genes that are highly expressed in lung cancer cells in comparison with normal cells. Thus, targeting BER-based therapy exhibits more selective cytotoxicity on cancer cells through a synthetic lethal mechanism. | Ali OY, Randell NM, Fridgen TD (2012)
Primary fragmentation pathways of gas phase [M(uracil-H)(uracil)]+ complexes (M=Zn, Cu, Ni, Co, Fe, Mn, Cd, Pd , Mg, Ca, Sr, Ba, and Pb): loss of uracil versus HNCO.
Chemphyschem : a European journal of chemical physics and physical chemistry 13, 1507-1513 [PubMed:22447672]
[show Abstract]
Complexes formed between metal dications, the conjugate base of uracil, and uracil are investigated by sustained off-resonance irradiation collision-induced dissociation (SORI-CID) in a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Positive-ion electrospray spectra show that [M(Ura-H)(Ura)](+) (M=Zn, Cu, Ni, Co, Fe, Mn, Cd, Pd, Mg, Ca, Sr, Ba, or Pb) is the most abundant ion even at low concentrations of uracil. SORI-CID experiments show that the main primary decomposition pathway for all [M(Ura-H)(Ura)](+) , except where M=Ca, Sr, Ba, or Pb, is the loss of HNCO. Under the same SORI-CID conditions, when M is Ca, Sr, Ba, or Pb, [M(Ura-H)(Ura)](+) are shown to lose a molecule of uracil. Similar results were observed under infrared multiple-photon dissociation excitation conditions, except that [Ca(Ura-H)(Ura)](+) was found to lose HNCO as the primary fragmentation product. The binding energies between neutral uracil and [M(Ura-H)](+) (M=Zn, Cu, Ni, Fe, Cd, Pd ,Mg, Ca, Sr Ba, or Pb) are calculated by means of electronic-structure calculations. The differences in the uracil binding energies between complexes which lose uracil and those which lose HNCO are consistent with the experimentally observed differences in fragmentation pathways. A size dependence in the binding energies suggests that the interaction between uracil and [M(Ura-H)](+) is ion-dipole complexation and the experimental evidence presented supports this. | Doseth B, Ekre C, Slupphaug G, Krokan HE, Kavli B (2012)
Strikingly different properties of uracil-DNA glycosylases UNG2 and SMUG1 may explain divergent roles in processing of genomic uracil.
DNA repair 11, 587-593 [PubMed:22483865]
[show Abstract]
Genomic uracil resulting from spontaneously deaminated cytosine generates mutagenic U:G mismatches that are usually corrected by error-free base excision repair (BER). However, in B-cells, activation-induced cytosine deaminase (AID) generates U:G mismatches in hot-spot sequences at Ig loci. These are subject to mutagenic processing during somatic hypermutation (SHM) and class switch recombination (CSR). Uracil N-glycosylases UNG2 and SMUG1 (single strand-selective monofunctional uracil-DNA glycosylase 1) initiate error-free BER in most DNA contexts, but UNG2 is also involved in mutagenic processing of AID-induced uracil during the antibody diversification process, the regulation of which is not understood. AID is strictly single strand-specific. Here we show that in the presence of Mg2+ and monovalent salts, human and mouse SMUG1 are essentially double strand-specific, whereas UNG2 efficiently removes uracil from both single and double stranded DNA under all tested conditions. Furthermore, SMUG1 and UNG2 display widely different sequence preferences. Interestingly, uracil in a hot-spot sequence for AID is 200-fold more efficiently removed from single stranded DNA by UNG2 than by SMUG1. This may explain why SMUG1, which is not excluded from Ig loci, is unable to replace UNG2 in antibody diversification. We suggest a model for mutagenic processing in which replication protein A (RPA) recruits UNG2 to sites of deamination and keeps DNA in a single stranded conformation, thus avoiding error-free BER of the deaminated cytosine. | Wang T, Bowie JH (2012)
Can cytosine, thymine and uracil be formed in interstellar regions? A theoretical study.
Organic & biomolecular chemistry 10, 652-662 [PubMed:22120518]
[show Abstract]
This theoretical study investigates possible synthetic routes to cytosine, uracil and thymine in the gas phase from precursor molecules that have been detected in interstellar media. Studies at the CCSD(T)/6-311++G(d,p)//B3LYP/6-311++G(d,p) level of theory suggest that: The reactions between :CCCNH and :CCCO with monosolvated urea may constitute viable interstellar syntheses of cytosine and uracil. No low energy equilibration between cytosine and uracil has been demonstrated. The interaction of :CH(2) with the 5 C-H bond of uracil may form thymine in an energetically favourable reaction, but competing reactions where :CH(2) reacts with double bonds and other CH and NH bonds of uracil, reduce the effectiveness of this synthesis. The reaction between the hydrated propional enolate anion and isocyanic acid may produce thymine, in a reaction sequence where ΔG(reaction)(298 K) is -22 kJ mol(-1) and the maximum energy requirement (barrier to the first transition state) is only 47 kJ mol(-1). | Muha V, Horváth A, Békési A, Pukáncsik M, Hodoscsek B, Merényi G, Róna G, Batki J, Kiss I, Jankovics F, Vilmos P, Erdélyi M, Vértessy BG (2012)
Uracil-containing DNA in Drosophila: stability, stage-specific accumulation, and developmental involvement.
PLoS genetics 8, e1002738 [PubMed:22685418]
[show Abstract]
Base-excision repair and control of nucleotide pools safe-guard against permanent uracil accumulation in DNA relying on two key enzymes: uracil-DNA glycosylase and dUTPase. Lack of the major uracil-DNA glycosylase UNG gene from the fruit fly genome and dUTPase from fruit fly larvae prompted the hypotheses that i) uracil may accumulate in Drosophila genomic DNA where it may be well tolerated, and ii) this accumulation may affect development. Here we show that i) Drosophila melanogaster tolerates high levels of uracil in DNA; ii) such DNA is correctly interpreted in cell culture and embryo; and iii) under physiological spatio-temporal control, DNA from fruit fly larvae, pupae, and imago contain greatly elevated levels of uracil (200-2,000 uracil/million bases, quantified using a novel real-time PCR-based assay). Uracil is accumulated in genomic DNA of larval tissues during larval development, whereas DNA from imaginal tissues contains much less uracil. Upon pupation and metamorphosis, uracil content in DNA is significantly decreased. We propose that the observed developmental pattern of uracil-DNA is due to the lack of the key repair enzyme UNG from the Drosophila genome together with down-regulation of dUTPase in larval tissues. In agreement, we show that dUTPase silencing increases the uracil content in DNA of imaginal tissues and induces strong lethality at the early pupal stages, indicating that tolerance of highly uracil-substituted DNA is also stage-specific. Silencing of dUTPase perturbs the physiological pattern of uracil-DNA accumulation in Drosophila and leads to a strongly lethal phenotype in early pupal stages. These findings suggest a novel role of uracil-containing DNA in Drosophila development and metamorphosis and present a novel example for developmental effects of dUTPase silencing in multicellular eukaryotes. Importantly, we also show lack of the UNG gene in all available genomes of other Holometabola insects, indicating a potentially general tolerance and developmental role of uracil-DNA in this evolutionary clade. | Tseng CH, Sándor P, Kotur M, Weinacht TC, Matsika S (2012)
Two-dimensional fourier transform spectroscopy of adenine and uracil using shaped ultrafast laser pulses in the deep UV.
The journal of physical chemistry. A 116, 2654-2661 [PubMed:22074393]
[show Abstract]
We compare two-dimensional (2D) ultrafast Fourier transform spectroscopy measurements in the deep UV (262 nm) for adenine and uracil in solution. Both molecules show excited-state absorption on short time scales and ground-state bleaching extending for over 1 ps. While the 2D spectrum for uracil shows changes in the center of gravity during the first few hundred femtoseconds, the center of gravity of the 2D spectrum for adenine does not show similar changes. We discuss our results in light of ab initio electronic structure calculations. | Yamazaki S, Taketsugu T (2012)
Nonradiative deactivation mechanisms of uracil, thymine, and 5-fluorouracil: a comparative ab initio study.
The journal of physical chemistry. A 116, 491-503 [PubMed:22171528]
[show Abstract]
The mechanisms of the ultrafast nonradiative deactivation of uracil and its substituted derivatives thymine (5-methyluracil) and 5-fluorouracil after absorption of UV light are explored and compared by means of ab initio multistate (MS) CASPT2 calculations. The MS-CASPT2 method is applied for the calculation of potential energy profiles, especially for the geometry optimization in the electronically excited state, with the aim of an accurate prediction of deactivation pathways. The resulting energy curves of each molecule exhibit that the conical intersection between the (1)ππ* and ground states is accessible via small energy barriers from the minimum in the (1)ππ* state as well as from that in the (1)nπ* state. The barrier of 5-fluorouracil in the (1)ππ* state is calculated to be definitely higher than those of uracil and thymine, which is consistent with experiments and suggests that the elongation of the excited-state lifetime of uracil by fluorine substitution is significantly contributed from intrinsic electronic effect of the molecule. However, no evidence of the experimentally observed longer excited-state lifetime of thymine than uracil is found in the presently calculated MS-CASPT2 potential energy curves in the (1)ππ* and (1)nπ* states, implying nonnegligible contribution of other factors such as solvation effect and substituent mass to the photoinduced dynamics of uracil derivatives. | Melicherčík M, Pašteka LF, Neogrády P, Urban M (2012)
Electron affinities of uracil: microsolvation effects and polarizable continuum model.
The journal of physical chemistry. A 116, 2343-2351 [PubMed:22299724]
[show Abstract]
We present adiabatic electron affinities (AEAs) and the vertical detachment energies (VDEs) of the uracil molecule interacting with one to five water molecules. Credibility of MP2 and DFT/B3LYP calculations is supported by comparison with available benchmark CCSD(T) data. AEAs and VDEs obtained by MP2 and DFT/B3LYP methods copy trends of benchmark CCSD(T) results for the free uracil and uracil-water complexes in the gas phase being by 0.20 - 0.28 eV higher than CCSD(T) values depending on the particular structure of the complex. AEAs and VDEs from MP2 are underestimated by 0.09-0.15 eV. For the free uracil and uracil-(H(2)O)(n) (n = 1,2,3,5) complexes, we also consider the polarizable continuum model (PCM) and discuss the importance of the microsolvation when combined with PCM. AEAs and VDEs of uracil and uracil-water complexes enhance rapidly with increasing relative dielectric constant (ε) of the solvent. Highest AEAs and VDEs of the U(H(2)O)(5) complexes from B3LYP with ε = 78.4 are 2.03 and 2.81 eV, respectively, utilizing the correction from CCSD(T). Specific structural features of the microsolvated uracil-(H(2)O)(n) complexes and their anions are preserved also upon considering PCM in calculations of AEAs and VDEs. | Gillis EA, Rajabi K, Fridgen TD (2009)
Structures of hydrated Li+-thymine and Li+-uracil complexes by IRMPD spectroscopy in the N-H/O-H stretching region.
The journal of physical chemistry. A 113, 824-832 [PubMed:19175333]
[show Abstract]
The interaction of lithium ions with two pyrimidine nucleobases, thymine and uracil, as well as the solvation of various complexes by one and two water molecules, has been studied in the gas phase. IRMPD spectra are reported for each of B-Li(+)-(H(2)O)(n) (n = 1-2) and B(2)-Li-(H(2)O)(m) (m = 0-1) for B = thymine, uracil over the 2500-4000 cm(-1) region. Calculations were performed using the B3LYP density functional in conjunction with the 6-31+G(d,p) basis set to model the vibrational spectra as well as MP2/6-311++G(2d,p) theory to model the thermochemistry of potential structures. Experimental and theoretical results were used in combination to determine structures of each complex, which are reported here. The lithium cation in all complexes was found to bond to the O4 oxygen in both thymine and uracil, and the first two water molecules of solvation were found to bond to Li(+). The experimental spectra obtained for BLi(+)(H(2)O)(n) (n = 1-2) and B(2)Li(+) for thymine and uracil clearly resemble one another, suggesting similar structural features in terms of bonding between the base and Li(+), as well as for solvation. This was confirmed through theoretical work. The addition of water to the lithium ion-bound DNA base dimers has been shown to induce a significant change in structure of the dimer to a hydrogen-bonded system similar to base pairing in the Watson-Crick model of DNA. | Zhang B, Pan X, Stellwag EJ (2008)
Identification of soybean microRNAs and their targets.
Planta 229, 161-182 [PubMed:18815805]
[show Abstract]
The microRNAs (miRNAs) are a newly identified class of small non-protein-coding regulatory RNA. Using comparative genomics, we identified 69 miRNAs belonging to 33 families in the domesticated soybean (Glycine max) as well as five miRNAs in the soybean wild species Glycine soja and Glycine clandestine. TaqMan((R)) MicroRNA Assay analyses demonstrated that these miRNAs were differentially expressed in soybean tissues, with certain classes expressed preferentially in both a spatiotemporal and a tissue-specific manner. Detailed sequence analyses revealed that soybean pre-miRNAs vary in length from 44 to 259 nt with an average of 106 +/- 45 nt, harbor mature miRNAs that differ in their physical location within the pre-miRNAs, and encode more than a single mature miRNA. Comparative sequence analyses of soybean miRNA sequences showed that uracil is the dominant base in the first position at the 5' end of the mature miRNAs while cytosine is dominant at the 19th position, which is indicative that these two bases may have an important functional role in miRNA biogenesis and/or miRNA-mediated gene regulation. Soybeans were unique among plants in the frequency of occurrence of miRNA clusters. For the first time, antisense miRNAs were identified in plants. The five antisense miRNAs and their sense partners from soybean belonged to three miRNA families (miR-157, miR-162 and miR-396). Antisense miRNAs were also identified in soybean wild species. Mature antisense miRNA products appeared to have 1-3 nucleotide changes compared to their sense partners, which suggests that both strands of a miRNA gene can produce functional mature miRNAs and that antisense transcripts may differ functionally from their sense partners. Based on previously established in silico methods, we predicted 152 miRNA-targeted mRNAs, which included a large percentage of mRNAs that encode transcription factors that regulate plant growth and development as well as a lesser percentage of mRNAs that encode environmental signal transduction proteins and central metabolic processes. | Sire J, Quérat G, Esnault C, Priet S (2008)
Uracil within DNA: an actor of antiviral immunity.
Retrovirology 5, 45 [PubMed:18533995]
[show Abstract]
Uracil is a natural base of RNA but may appear in DNA through two different pathways including cytosine deamination or misincorporation of deoxyuridine 5'-triphosphate nucleotide (dUTP) during DNA replication and constitutes one of the most frequent DNA lesions. In cellular organisms, such lesions are faithfully cleared out through several universal DNA repair mechanisms, thus preventing genome injury. However, several recent studies have brought some pieces of evidence that introduction of uracil bases in viral genomic DNA intermediates during genome replication might be a way of innate immune defence against some viruses. As part of countermeasures, numerous viruses have developed powerful strategies to prevent emergence of uracilated viral genomes and/or to eliminate uracils already incorporated into DNA. This review will present the current knowledge about the cellular and viral countermeasures against uracils in DNA and the implications of these uracils as weapons against viruses. | Castrillo JI, Zeef LA, Hoyle DC, Zhang N, Hayes A, Gardner DC, Cornell MJ, Petty J, Hakes L, Wardleworth L, Rash B, Brown M, Dunn WB, Broadhurst D, O'Donoghue K, Hester SS, Dunkley TP, Hart SR, Swainston N, Li P, Gaskell SJ, Paton NW, Lilley KS, Kell DB, Oliver SG (2007)
Growth control of the eukaryote cell: a systems biology study in yeast.
Journal of biology 6, 4 [PubMed:17439666]
[show Abstract]
BackgroundCell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking.ResultsMetabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth.ConclusionThis work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell. | Matsika S (2005)
Three-state conical intersections in nucleic acid bases.
The journal of physical chemistry. A 109, 7538-7545 [PubMed:16834123]
[show Abstract]
The involvement of three-state conical intersections in the photophysics and radiationless decay processes of the nucleobases has been investigated using multireference configuration interaction methods. Three-state conical intersections have been located for the pyrimidine base, uracil, and the purine base, adenine. In uracil, a three-state degeneracy between the S(0), S(1), and S(2) states has been located at 6.2 eV above the ground-state minimum energy. This energy is 0.4 eV higher than vertical excitation to S(2) and at least 1.3 eV higher than the two-state conical intersections found previously. In adenine, two different three-state degeneracies between the S(1), S(2), and S(3) states have been located at energies close to the vertical excitation energies. The energetics of these three-state conical intersections suggest they can play a role in a radiationless decay pathway present in adenine. The existence of two different seams of three-state conical intersections indicates that these features are common and complicate the potential energy surfaces of adenine and possibly many other aromatic molecules. | Wang J, Yang M, Yagi S, Hoffman RM (2004)
Oral 5-FU is a more effective antimetastatic agent than UFT.
Anticancer research 24, 1353-1360 [PubMed:15274295]
[show Abstract]
5-Fluorouracil (5-FU), a pyrimidine analog, is widely used to treat gastrointestinal and other cancers. In the present study, we compared the efficacy of oral 5-FU and the 5-FU prodrug, uracil plus tegafur (UFT), on liver metastasis in a highly metastatic mouse model. Genetic labeling of the tumor with green fluorescent protein (GFP) along with inexpensive video detectors, positioned external to the mouse, allowed the real-time monitoring of details of tumor growth, metastatic spread and drug response in this mouse model. 5-FU at 10 and 20 mg/kg significantly prolonged the survival time of treated animals compared with untreated controls (p=0.003 for 5-FU, 10 mg/kg; p=0.016 for 5-FU, 20 mg/kg). In contrast, UFT only showed a trend to increase survival (p=0.078). 5-FU at 10 mg/kg substantially prolonged the survival time compared to UFT (p=0.012). 5-FU (10 mg/kg) was also more effective in prolonging survival than Furtulon (5'-deoxy-5-fluorouridine, another 5-FU prodrug) (p=0.042). All control and UFT-treated animals died by day 45. In contrast, at 45 days, 5 out of 8 animals were alive in the 5-FU 10 mg/kg group, which was found to be the best treatment regimen in this study. 5-FU (10 mg/kg)-treated animals had a median survival time of 53 days compared to 26.5 in controls and 33.5 days for UFT. These results suggest the potential clinical superiority of oral 5-FU compared to UFT as an anti-metastatic agent. The data also suggest the lack of clinical need for complex and expensive prodrugs of 5-FU such as UFT. | Acharya N, Kumar P, Varshney U (2003)
Complexes of the uracil-DNA glycosylase inhibitor protein, Ugi, with Mycobacterium smegmatis and Mycobacterium tuberculosis uracil-DNA glycosylases.
Microbiology (Reading, England) 149, 1647-1658 [PubMed:12855717]
[show Abstract]
Uracil, a promutagenic base, appears in DNA either by deamination of cytosine or by incorporation of dUMP by DNA polymerases. This unconventional base in DNA is removed by uracil-DNA glycosylase (UDG). Interestingly, a bacteriophage-encoded short polypeptide, UDG inhibitor (Ugi), specifically inhibits UDGs by forming a tight complex. Three-dimensional structures of the complexes of Ugi with UDGs from Escherichia coli, human and herpes simplex virus have shown that two of the structural elements in Ugi, the hydrophobic pocket and the beta1-edge, establish key interactions with UDGs. In this report the characterization of complexes of Ugi with UDGs from Mycobacterium tuberculosis, a pathogenic bacterium, and Mycobacterium smegmatis, a widely used model organism for the former, is described. Unlike the E. coli (Eco) UDG-Ugi complex, which is stable to treatment with 8 M urea, the mycobacterial UDG-Ugi complexes dissociate in 5-6 M urea. Furthermore, the Ugi from the complexes of mycobacterial UDGs can be exchanged by the DNA substrate. Interestingly, while EcoUDG sequestered Ugi into the EcoUDG-Ugi complex when incubated with mycobacterial UDG-Ugi complexes, even a large excess of mycobacterial UDGs failed to sequester Ugi from the EcoUDG-Ugi complex. However, the M. tuberculosis (Mtu) UDG-Ugi complex was seen when MtuUDG was incubated with M. smegmatis (Msm) UDG-Ugi or EcoUDG(L191G)-Ugi complexes. The reversible nature of the complexes of Ugi with mycobacterial UDGs (which naturally lack some of the structural elements important for interaction with the beta1-edge of Ugi) and with mutants of EcoUDG (which are deficient in interaction with the hydrophobic pocket of Ugi) highlights the significance of both classes of interaction in formation of UDG-Ugi complexes. Furthermore, it is shown that even though mycobacterial UDG-Ugi complexes dissociate in 5-6 M urea, Ugi is still a potent inhibitor of UDG activity in mycobacteria. | Handa P, Acharya N, Varshney U (2001)
Chimeras between single-stranded DNA-binding proteins from Escherichia coli and Mycobacterium tuberculosis reveal that their C-terminal domains interact with uracil DNA glycosylases.
The Journal of biological chemistry 276, 16992-16997 [PubMed:11279060]
[show Abstract]
Uracil, a promutagenic base in DNA can arise by spontaneous deamination of cytosine or incorporation of dUMP by DNA polymerase. Uracil is removed from DNA by uracil DNA glycosylase (UDG), the first enzyme in the uracil excision repair pathway. We recently reported that the Escherichia coli single-stranded DNA binding protein (SSB) facilitated uracil excision from certain structured substrates by E. coli UDG (EcoUDG) and suggested the existence of interaction between SSB and UDG. In this study, we have made use of the chimeric proteins obtained by fusion of N- and C-terminal domains of SSBs from E. coli and Mycobacterium tuberculosis to investigate interactions between SSBs and UDGs. The EcoSSB or a chimera containing its C-terminal domain interacts with EcoUDG in a binary (SSB-UDG) or a ternary (DNA-SSB-UDG) complex. However, the chimera containing the N-terminal domain from EcoSSB showed no interactions with EcoUDG. Thus, the C-terminal domain (48 amino acids) of EcoSSB is necessary and sufficient for interaction with EcoUDG. The data also suggest that the C-terminal domain (34 amino acids) of MtuSSB is a predominant determinant for mediating its interaction with MtuUDG. The mechanism of how the interactions between SSB and UDG could be important in uracil excision repair pathway has been discussed. | Harle DG, Baldo BA, Smal MA, Fisher MM (1987)
Drugs as allergens: the molecular basis of IgE binding to thiopentone.
International archives of allergy and applied immunology 84, 277-283 [PubMed:3654008]
[show Abstract]
Using an immunoassay developed for the detection of thiopentone-reactive IgE antibodies, the combining site specificities of such antibodies found in sera of patients who experienced life-threatening anaphylactic reactions to the drug were studied. The antibody combining sites from one patient were complementary to the region of the thiopentone molecule containing a thio group at position 2 of the barbiturate ring. The allergenic determinant recognized by IgE antibodies from another patient encompassed a secondary pentyl group and an ethyl group attached to position 5 on the other side of the barbiturate ring. Thus, it is already clear that there is more than one allergenic determinant on the thiopentone molecule with the capacity to provoke IgE formation and drug-induced allergic reactions. |
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