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Record Information
Version2.0
Creation Date2014-08-29 06:51:15 UTC
Update Date2018-03-21 17:46:23 UTC
Accession NumberT3D4430
Identification
Common NameDeoxyuridine triphosphate
ClassSmall Molecule
DescriptionDeoxyuridine triphosphate (dUTP) is a deoxynucleotide triphosphate (dNTP) that is chemically similar to uridine triphosphate (UTP) except that it has a deoxyribose sugar instead of a ribose sugar. DNA synthesis requires the availability of deoxynucleotide triphosphates (dTTP, dATP, dGTP, dCTP), whereas RNA synthesis requires the availability of nucleotide triphosphates (NTPs) such as TTP, ATP, GTP, and UTP. The conversion of nucleotide triphosphates (NTPs) into dNTPs can only be done in the diphosphate form. Typically, an NTP has one phosphate removed to become an NDP. This is then converted into a dNDP by an enzyme called ribonucleotide reductase and followed by the re-addition of phosphate to give a dNTP. dUTP is a substrate for several enzymes, including inosine triphosphate pyrophosphatase, deoxyuridine 5'-triphosphate nucleotidohydrolase (mitochondrial), uridine-cytidine kinase 1, nucleoside diphosphate kinase 3, nucleoside diphosphate kinase B, nucleoside diphosphate kinase 6, nucleoside diphosphate kinase (mitochondrial), nucleoside diphosphate kinase homolog 5, nucleoside diphosphate kinase A, and nucleoside diphosphate kinase 7. While UTP is routinely incorporated into RNA, dUTP is not normally incorporated into DNA. Instead, if dUTP is misincorporated into DNA, it can cause DNA damage. Therefore, dUTP can be considered as a teratogen or a mutagen. The extent of DNA damage caused by dUTP is highly dependent on the levels of the dUTP pyrophosphatase (dUTPase) and uracil-DNA glycosylase (UDG), which limits the intracellular accumulation of dUTP. Additionally, loss of viability following thymidylate synthase (TS) inhibition occurs as a consequence of the accumulation of dUTP in some cell lines and subsequent misincorporation of uracil into DNA (PMID: 11487279).
Compound Type
  • Amine
  • Animal Toxin
  • Ether
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2'-Deoxyuridine 5'-triphosphate
2'-Deoxyuridine-5'-triphosphorate
2'-Deoxyuridine-5'-triphosphoric acid
2'-Deoxyuridine-5'-triphosphoric acid = dUTP
Deoxy-UTP
Deoxyuridine triphosphic acid
Deoxyuridine-5'-Triphosphate
dUTP
Chemical FormulaC9H15N2O14P3
Average Molecular Mass468.142 g/mol
Monoisotopic Mass467.974 g/mol
CAS Registry Number1173-82-6
IUPAC Name({[({[(2R,3S,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid
Traditional NamedUTP
SMILES[H][C@]1(O)C[C@@]([H])(O[C@]1([H])COP(O)(=O)OP(O)(=O)OP(O)(O)=O)N1C=CC(O)=NC1=O
InChI IdentifierInChI=1S/C9H15N2O14P3/c12-5-3-8(11-2-1-7(13)10-9(11)14)23-6(5)4-22-27(18,19)25-28(20,21)24-26(15,16)17/h1-2,5-6,8,12H,3-4H2,(H,18,19)(H,20,21)(H,10,13,14)(H2,15,16,17)/t5-,6+,8+/m0/s1
InChI KeyInChIKey=AHCYMLUZIRLXAA-SHYZEUOFSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleoside triphosphates. These are pyrimidine nucleotides with a triphosphate group linked to the ribose moiety lacking a hydroxyl group at position 2.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleotides
Sub ClassPyrimidine deoxyribonucleotides
Direct ParentPyrimidine 2'-deoxyribonucleoside triphosphates
Alternative Parents
Substituents
  • Pyrimidine 2'-deoxyribonucleoside triphosphate
  • Pyrimidone
  • Monoalkyl phosphate
  • Hydroxypyrimidine
  • Hydropyrimidine
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Pyrimidine
  • Alkyl phosphate
  • Tetrahydrofuran
  • Heteroaromatic compound
  • Secondary alcohol
  • Organoheterocyclic compound
  • Azacycle
  • Oxacycle
  • Organopnictogen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Alcohol
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Membrane
  • Mitochondria
  • Nucleus
Biofluid LocationsNot Available
Tissue Locations
  • Epidermis
  • Muscle
  • Prostate
  • Spleen
Pathways
NameSMPDB LinkKEGG Link
Pyrimidine MetabolismSMP00046 map00240
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)SMP00202 Not Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility8.63 g/LALOGPS
logP-0.12ALOGPS
logP-2.5ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)0.9ChemAxon
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area238.69 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity83.67 m³·mol⁻¹ChemAxon
Polarizability34.62 ųChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4j-8963100000-15f9b7594aa45581dcc0JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-05be-9551020000-12e307f13199997c5947JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0900000000-9dfd5f9811270d9aaab8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-3911000000-b480c4f463f71544be8fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-5900000000-2ba3b00121251c9adda0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-01b9-3120900000-dedbedae66448a647f3bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-057u-9430100000-0b81cc8084e6bd0f3088JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-9510000000-a72cd2e823cab077b0e1JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityDeoxyuridine triphosphate (dUTP) can be misincorporated into DNA and cause DNA damage. The extent of DNA damage caused by dUTP is dependent on the levels of the pyrophosphatase dUTPase and uracil-DNA glycosylase (UDG). DNA damage due to dUTP misincorporation is highly dependent on the levels of the pyrophosphatase dUTPase, which limits intracellular accumulation of dUTP. (9) Also, loss of viability following thymidylate synthase (TS) inhibition occurs as a consequence of accumulation of dUTP in some cell lines and subsequent misincorporation of uracil into DNA. (PMCID: PMC2364072)
MetabolismMetabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02333
HMDB IDHMDB01191
PubChem Compound ID65070
ChEMBL IDCHEMBL374361
ChemSpider ID58580
KEGG IDC00460
UniProt IDNot Available
OMIM ID
ChEBI ID17625
BioCyc IDDUTP
CTD IDNot Available
Stitch IDNot Available
PDB IDDUT
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Ge YF, Huang YF, Zhang GY, Wang XH, Xu JP: Studies on apoptosis of spermatogenic cells in normal fertile men treated with supraphysiological doses of testosterone undecanoate. Asian J Androl. 1999 Sep;1(3):155-8. [11250785 ]
  2. Gilhar A, Ullmann Y, Karry R, Shalaginov R, Assy B, Serafimovich S, Kalish RS: Ageing of human epidermis: the role of apoptosis, Fas and telomerase. Br J Dermatol. 2004 Jan;150(1):56-63. [14746617 ]
  3. Igarashi T, Brown CR, Byrum RA, Nishimura Y, Endo Y, Plishka RJ, Buckler C, Buckler-White A, Miller G, Hirsch VM, Martin MA: Rapid and irreversible CD4+ T-cell depletion induced by the highly pathogenic simian/human immunodeficiency virus SHIV(DH12R) is systemic and synchronous. J Virol. 2002 Jan;76(1):379-91. [11739702 ]
  4. Russell J, O'Donoghue JA, Finn R, Koziorowski J, Ruan S, Humm JL, Ling CC: Iodination of annexin V for imaging apoptosis. J Nucl Med. 2002 May;43(5):671-7. [11994533 ]
  5. Oosterhuis GJ, Mulder AB, Kalsbeek-Batenburg E, Lambalk CB, Schoemaker J, Vermes I: Measuring apoptosis in human spermatozoa: a biological assay for semen quality? Fertil Steril. 2000 Aug;74(2):245-50. [10927039 ]
  6. Lee AY, Youm YH, Kim NH, Yang H, Choi WI: Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis. Br J Dermatol. 2004 Nov;151(5):995-1003. [15541077 ]
  7. Lamperti C, Naini AB, Lucchini V, Prelle A, Bresolin N, Moggio M, Sciacco M, Kaufmann P, DiMauro S: Muscle coenzyme Q10 level in statin-related myopathy. Arch Neurol. 2005 Nov;62(11):1709-12. [16286544 ]
  8. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
  9. Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [12724731 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
General Function:
Uracil dna n-glycosylase activity
Specific Function:
Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Gene Name:
UNG
Uniprot ID:
P13051
Molecular Weight:
34645.27 Da