Deoxyadenosine triphosphate

Deoxyadenosine triphosphate
Skeletal formula of deoxyadenosine triphosphate
Ball-and-stick model of the deoxyadenosine triphosphate anion
Names
IUPAC name
[[(2R,3S,5R)-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
Other names
dATP, 2'-deoxyadenosine triphosphate
Identifiers
CAS Number
  • 1927-31-7 checkY
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:16284 checkY
ChEMBL
  • ChEMBL335538 checkY
ChemSpider
  • 15194 checkY=  checkY=  checkY=  ☒N
ECHA InfoCard 100.016.058 Edit this at Wikidata
IUPHAR/BPS
  • 1760
PubChem CID
  • 15993
CompTox Dashboard (EPA)
  • DTXSID10895848 Edit this at Wikidata
InChI
  • InChI=1S/C10H16N5O12P3/c11-9-8-10(13-3-12-9)15(4-14-8)7-1-5(16)6(25-7)2-24-29(20,21)27-30(22,23)26-28(17,18)19/h3-7,16H,1-2H2,(H,20,21)(H,22,23)(H2,11,12,13)(H2,17,18,19)/t5-,6+,7+/m0/s1 checkY=  checkY
    Key: SUYVUBYJARFZHO-RRKCRQDMSA-N checkY=  checkY
  • InChI=1/C10H16N5O12P3/c11-9-8-10(13-3-12-9)15(4-14-8)7-1-5(16)6(25-7)2-24-29(20,21)27-30(22,23)26-28(17,18)19/h3-7,16H,1-2H2,(H,20,21)(H,22,23)(H2,11,12,13)(H2,17,18,19)/t5-,6+,7+/m0/s1
    Key: SUYVUBYJARFZHO-RRKCRQDMBD
  • O=P(O)(O)OP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n2cnc1c(ncnc12)N)C[C@@H]3O
Properties
Chemical formula
 C10H16N5O12P3
Molar mass 491.181623
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references
Chemical compound

Deoxyadenosine triphosphate (dATP) is a nucleotide used in cells for DNA synthesis (or replication), as a substrate of DNA polymerase.[1]

Deoxyadenosine triphosphate is produced from DNA by the action of nuclease P1, adenylate kinase, and pyruvate kinase.[2]

Health effects

High levels of dATP can be toxic and result in impaired immune function, since dATP acts as a noncompetitive inhibitor for the DNA synthesis enzyme ribonucleotide reductase. Patients with adenosine deaminase deficiency (ADA) tend to have elevated intracellular dATP concentrations because adenosine deaminase normally curbs adenosine levels by converting it into inosine.[3][4] Deficiency of this deaminase also causes immunodeficiency.[5]

In cardiac myosin, dATP is an alternative to ATP as an energy substrate for facilitating cross-bridge formation.[6][7]

See also

References

  1. ^ Romaniuk PJ, Eckstein F (July 1982). "A study of the mechanism of T4 DNA polymerase with diastereomeric phosphorothioate analogues of deoxyadenosine triphosphate". The Journal of Biological Chemistry. 257 (13): 7684–7688. doi:10.1016/S0021-9258(18)34435-1. PMID 7045112.
  2. ^ Ladner WE, Whitesides GM (1985-04-01). "Enzymic synthesis of deoxyATP using DNA as starting material". The Journal of Organic Chemistry. 50 (7): 1076–1079. doi:10.1021/jo00207a032. ISSN 0022-3263.
  3. ^ Chang CH, Cheng YC (October 1980). "Effects of deoxyadenosine triphosphate and 9-beta-D-arabinofuranosyl-adenine 5'-triphosphate on human ribonucleotide reductase from Molt-4F cells and the concept of "self-potentiation"". Cancer Research. 40 (10): 3555–3558. PMID 6159965.
  4. ^ Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R, Martin DW (January 1978). "Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency". Proceedings of the National Academy of Sciences of the United States of America. 75 (1): 472–476. Bibcode:1978PNAS...75..472C. doi:10.1073/pnas.75.1.472. PMC 411272. PMID 272665.
  5. ^ Sanchez JJ, Monaghan G, Børsting C, Norbury G, Morling N, Gaspar HB (May 2007). "Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry". Annals of Human Genetics. 71 (Pt 3): 336–347. doi:10.1111/j.1469-1809.2006.00338.x. PMID 17181544. S2CID 34850391.
  6. ^ Cheng Y, Hogarth KA, O'Sullivan ML, Regnier M, Pyle WG (January 2016). "2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy". American Journal of Physiology. Heart and Circulatory Physiology. 310 (1): H80–H91. doi:10.1152/ajpheart.00530.2015. PMC 4796460. PMID 26497964.
  7. ^ Powers JD, Yuan CC, McCabe KJ, Murray JD, Childers MC, Flint GV, et al. (June 2019). "Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin". Proceedings of the National Academy of Sciences of the United States of America. 116 (23): 11502–11507. Bibcode:2019PNAS..11611502P. doi:10.1073/pnas.1905028116. PMC 6561254. PMID 31110001.

Further reading

  • Ullman B, Gudas LJ, Cohen A, Martin DW (June 1978). "Deoxyadenosine metabolism and cytotoxicity in cultured mouse T lymphoma cells: a model for immunodeficiency disease". Cell. 14 (2): 365–375. doi:10.1016/0092-8674(78)90122-8. PMID 208780. S2CID 41048417.
  • Joachims ML, Marble PA, Laurent AB, Pastuszko P, Paliotta M, Blackburn MR, Thompson LF (December 2008). "Restoration of adenosine deaminase-deficient human thymocyte development in vitro by inhibition of deoxynucleoside kinases". Journal of Immunology. 181 (11): 8153–8161. doi:10.4049/jimmunol.181.11.8153. PMC 2673198. PMID 19018008.
  • Cowan MJ, Wara DW, Ammann AJ (October 1985). "Deoxycytidine therapy in two patients with adenosine deaminase deficiency and severe immunodeficiency disease". Clinical Immunology and Immunopathology. 37 (1): 30–36. doi:10.1016/0090-1229(85)90132-1. PMID 3161676.
  • Nakashima K, Nakashima H, Shimoyama M (September 1991). "Deoxyadenosine triphosphate acting as an energy-transferring molecule in adenosine deaminase inhibited human erythrocytes". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1094 (3): 257–262. doi:10.1016/0167-4889(91)90084-b. PMID 1911876.

External links

  • v
  • t
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Nucleic acid constituents
NucleobaseNucleoside
Ribonucleoside
Deoxyribonucleoside
Nucleotide
(Nucleoside monophosphate)
Ribonucleotide
Deoxyribonucleotide
Cyclic nucleotide
Nucleoside diphosphate
Nucleoside triphosphate
  • v
  • t
  • e
Receptor
(ligands)
P0 (adenine)
P1
(adenosine)
P2
(nucleotide)
P2X
(ATPTooltip Adenosine triphosphate)
P2Y
Transporter
(blockers)
CNTsTooltip Concentrative nucleoside transporters
ENTsTooltip Equilibrative nucleoside transporters
PMATTooltip Plasma membrane monoamine transporter
Enzyme
(inhibitors)
XOTooltip Xanthine oxidase
Others
Others
See also: Receptor/signaling modulators