Decitabine triphosphate incorporates into DNA

Stable Identifier
R-HSA-9710480
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Cellular uptake of decitabine or 5‑aza‑2′‑deoxycytidine is mediated by the equilibrative nucleoside transporters hENT1, hENT2, and hENT3, which also mediate cytosine uptake. Decitabine is a prodrug that has to be converted into a nucleoside triphosphate to become an active drug (reviewed in Raynal NJM & Issa JPJ 2016). The activation of the prodrug relies on three successive phosphorylation steps. The first phosphorylation is catalyzed by the deoxycytidine kinase (DCK) to produce the monophosphorylated form of decitabine or 5‑aza‑deoxycytidine‑5′‑monophosphate (5‑aza‑dCMP). Subsequently, two additional phosphorylation reactions catalyzed by the deoxycytidine‑5′‑monophosphate (dCMP) kinase and the nucleoside diphosphokinase will produce 5‑aza‑deoxycytidine‑5′‑diphosphate (5‑aza‑dCDP) and 5‑aza‑deoxycytidine‑5′‑triphosphate (5‑aza‑dCTP), respectively. Once in its triphosphate form, the active drug can be incorporated into the DNA of dividing cells by DNA polymerase, in the reaction annotated here. DNA polymerase has similar affinities for dCTP and 5‑aza‑dCTP (Raynal NJM & Issa JPJ 2016).

Literature References
PubMed ID Title Journal Year
  Drug Discovery in Cancer Epigenetics

Egger, G, Arimondo, P

  2016
Participants
Participates
Catalyst Activity

DNA-directed DNA polymerase activity of DNA polymerase alpha:primase [nucleoplasm]

Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
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