Uracil

Source: Wikipedia, the free encyclopedia.
Not to be confused with uridine.
Uracil
Structural formula of uracil
Ball-and-stick model of uracil
Ball-and-stick model of uracil
Space-filling model of uracil
Space-filling model of uracil
Names
Preferred IUPAC name
Pyrimidine-2,4(1H,3H)-dione
Other names
  • 2-Oxy-4-oxypyrimidine
  • 2,4(1H,3H)-Pyrimidinedione
  • 2,4-Dihydroxypyrimidine
  • 2,4-Pyrimidinediol
Identifiers
3D model (
JSmol
)
3DMet
606623
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.000.565 Edit this at Wikidata
EC Number
  • 200-621-9
2896
IUPHAR/BPS
KEGG
RTECS number
  • YQ8650000
UNII
  • InChI=1S/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8) ☒N
    Key: ISAKRJDGNUQOIC-UHFFFAOYSA-N ☒N
  • lactim
    form: Oc1nccc(O)n1
Properties
C4H4N2O2
Molar mass 112.08676 g/mol
Appearance Solid
Density 1.32 g/cm3
Melting point 335 °C (635 °F; 608 K)[1]
Boiling point N/A – decomposes
Soluble
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 carcinogen and teratogen with chronic exposure
GHS labelling:
GHS07: Exclamation markGHS08: Health hazard
Warning
H315, H319, H335, H361
P201, P202, P261, P264, P271, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability (yellow): no hazard codeSpecial hazards (white): no code
1
1
Flash point Non-flammable
Related compounds
Related compounds
 Thymine
Cytosine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Uracil (

demethylated form of thymine
.

Uracil is a common and naturally occurring

bovine thymus and spleen, herring sperm, and wheat germ.[5] It is a planar, unsaturated compound that has the ability to absorb light.[6]

Uracil that was formed extraterrestrially has been detected in the

near-Earth asteroid,[8] and possibly on the surface of the moon Titan.[9] It has been synthesized under cold laboratory conditions similar to outer space, from pyrimidine embedded in water ice and exposed to ultraviolet light.[10]

Properties

In RNA, uracil

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.[6]

Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the molecule may have from the lack of formal

lactim structure. These tautomeric forms are predominant at pH
 7. The lactam structure is the most common form of uracil.

lactim
structure (right)

Uracil also recycles itself to form nucleotides by undergoing a series of phosphoribosyltransferase reactions.

β-alanine, carbon dioxide, and ammonia.[2]

C4H4N2O2→ H3NCH2CH2COO− + NH+4 + CO2

Oxidative degradation of uracil produces urea and maleic acid in the presence of H2O2 and Fe2+ or in the presence of diatomic oxygen and Fe2+.

Uracil is a

weak acid. The first site of ionization of uracil is not known.[12] The negative charge is placed on the oxygen anion and produces a pKa of less than or equal to 12. The basic pKa = −3.4, while the acidic pKa = 9.389. In the gas phase, uracil has four sites that are more acidic than water.[13]

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.[14]

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

Synthesis

Biological

See also: Pyrimidine metabolism

Organisms synthesize uracil, in the form of

ribose phosphate, forming UMP.[16]

Laboratory

There are many laboratory synthesis of uracil available. The first reaction is the simplest of the syntheses, by adding water to cytosine to produce uracil and ammonia:[2]

C4H5N3O + H2O → C4H4N2O2 + NH3

The most common way to synthesize uracil is by the

fuming sulfuric acid:[5]

C4H4O4 + NH2CONH2 → C4H4N2O2 + 2 H2O + CO

Uracil can also be synthesized by a double decomposition of thiouracil in aqueous chloroacetic acid.[5]

Photodehydrogenation of 5,6-diuracil, which is synthesized by beta-alanine reacting with urea, produces uracil.[17]

Prebiotic

In 2009,

polycyclic aromatic hydrocarbons (PAHs), a carbon-rich chemical found in the Universe, may have been formed in red giants or in interstellar dust and gas clouds.[20]

Based on 12C/13C

near-Earth asteroid, with no exposure to Earth's biosphere, giving further evidence for synthesis in space.[8]

Reactions

Chemical structure of uridine

Uracil readily undergoes regular reactions including

ultraviolet light.[5] Uracil also has the capability to react with elemental halogens because of the presence of more than one strongly electron donating group.[5]

Uracil readily undergoes addition to ribose sugars and phosphates 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.[21] If the pH of the reaction increases to > 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.[21] The reactivity of uracil remains unchanged, even if the temperature changes.[21]

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.

deoxythymidine monophosphates (dTMP) and uracil misincorporation into DNA and eventually low production of DNA.[26]

Uracil can be used for

5-fluorouracil. 5-Fluorouracil is an anticancer drug (antimetabolite) used to masquerade as uracil during the nucleic acid replication process.[2] 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.[2] Uracil can also be used in the synthesis of caffeine.[27] Uracil has also shown potential as a HIV viral capsid inhibitor.[28] Uracil derivatives have antiviral, anti-tubercular and anti-leishmanial activity.[29][30][31]

Uracil can be used to determine

sunflower crops, vineyards, berry plantations, and orchards.[33] Uracil derivatives can enhance the activity of antimicrobial polysaccharides such as chitosan.[34]

In yeast, uracil concentrations are inversely proportional to uracil permease.[35]

Mixtures containing uracil are also commonly used to test reversed-phase 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

  1. ISBN 978-0-313-33758-1
    .
  2. ^ a b c d e f g Garrett RH, Grisham CM (1997). Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning.
  3. doi:10.1002/jlac.18852290102
    . Dasselbe stellt sich sonach als Methylderivat der Verbindung: welche ich willkürlich mit dem Namen Uracil belege, dar. [The same compound is therefore represented as the methyl derivative of the compound, which I will arbitrarily endow with the name ‘uracil’.]
  4. doi:10.1515/bchm2.1901.31.1-2.161. Archived from the original
    on 12 May 2018.
  5. ^
    ISBN 9780471506560. Archived
    from the original on 12 May 2018.
  6. ^
    ISBN 9780130266729
    .
  7. ^
    S2CID 14309508
    .
  8. ^
    PMID 36944653
    .
  9. ^
    Bibcode:2012DPS....4420102C
    .
  10. ^
    PMID 19778279
    .
  11. ^ "MadSciNet: The 24-hour exploding laboratory". www.madsci.org. Archived from the original on 18 July 2005.
  12. ISBN 9780471984184
    .
  13. PMID 12216739
    .
  14. ^ Békési A, Vértessy BG (2011). "Uracil in DNA: error or signal?". Science in School: 18. Archived from the original on 23 March 2016.
  15. PMID 2963806
    .
  16. ISBN 9780124437104
    .
  17. S2CID 4166393
    .
  18. ^ Marlaire R (5 November 2009). "NASA reproduces a building block of life in laboratory". NASA. Archived from the original on 4 March 2016. Retrieved 5 March 2015.
  19. S2CID 54189201
    .
  20. ^ Marlaire R (3 Mar 2015). "NASA Ames reproduces the building blocks of life in laboratory". NASA. Archived from the original on 5 March 2015. Retrieved 5 Mar 2015.
  21. ^
    ISBN 9781468429756
    .
  22. ^
    S2CID 9708198
    .
  23. PMID 21780761
    .
  24. PMID 19339377
    .
  25. PMID 22193538
    .
  26. ^
    PMID 15183762
    .
  27. S2CID 43220488
    .
  28. PMID 35765450
    .
  29. S2CID 231576801
    .
  30. S2CID 221724578
    .
  31. S2CID 246474821
    .
  32. PMID 15656671
    .
  33. ^
    ISBN 9780471960348
    .
  34. S2CID 248526212
    .
  35. PMID 10074071
    .

External links
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