Deoxyadenosine triphosphate explained

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

• Adenosine triphosphate (ATP)
• Adenosine deaminase deficiency (ADA)
• Dilated cardiomyopathy (DCM)

Further reading

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

External links

• KEGG entry on dATP

Notes and References

1. Romaniuk PJ, Eckstein F . 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 . July 1982 . 10.1016/S0021-9258(18)34435-1 . 7045112 . free .
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. 10.1021/jo00207a032. 0022-3263.
3. Chang CH, Cheng YC . 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 . October 1980 . 6159965 .
4. Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R, Martin DW . 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 . January 1978 . 272665 . 10.1073/pnas.75.1.472 . 411272 . 1978PNAS...75..472C . free .
5. Sanchez JJ, Monaghan G, Børsting C, Norbury G, Morling N, Gaspar HB . 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 . May 2007 . 17181544 . 10.1111/j.1469-1809.2006.00338.x . 34850391 .
6. Cheng Y, Hogarth KA, O'Sullivan ML, Regnier M, Pyle WG . 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 . January 2016 . 26497964 . 4796460 . 10.1152/ajpheart.00530.2015 .
7. Powers JD, Yuan CC, McCabe KJ, Murray JD, Childers MC, Flint GV, Moussavi-Harami F, Mohran S, Castillo R, Zuzek C, Ma W, Daggett V, McCulloch AD, Irving TC, Regnier M . 6 . 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 . June 2019 . 31110001 . 10.1073/pnas.1905028116 . 6561254 . 2019PNAS..11611502P . free .