Cytosine arabinoside phosphorylation

This enzyme [EC 2.7.1.74] catalyzes the reaction of a nucleoside triphosphate with deoxycytidine to produce a nucleoside diphosphate and dCMP. This enzyme can use any nucleoside triphosphate (except dCTP) as the phosphate-donor substrate and it can phosphorylate cytosine arabinoside as well. 

Site of action Like the other purine and pyrimidine antagonists, ara-C must be sequentially phosphorylated to the corresponding nucleotide, cytosine arabinoside triphosphate (ara-CTP), in order to be cytotoxic. It is S-phase (hence cell-cycle) specific. Ara-C is also incorporated into DNA and can terminate chain elongation. It can also inhibit the reduction of CDP to dCDP. 

Cytarabine (cytosine arabinoside) is an analogue of 2 -deoxycytidine. The 2 -hydroxyl group of the arabinose moiety is in a trans position with respect to the 3 -hydroxyl group (instead of in a cis position, as in the ribose) and causes steric hindrance to rotation of the base around the nucleoside bond (Chapter 23). Phosphorylated derivatives of cytarabine inhibit nucleic acid synthesis as well as being incorporated into nucleic acids. 

Cytosine Arabinoside (1-B-D-arabinofuranosylcytosine, ara-C, cytara-bine) - Enzymatic phosphorylation studies confirm that ara-C and its phos-phorylated derivatives are deoxycytidine antagonists rather than cytidlne antagonists. 2 inhibition of DNA polymerase activity is considered more significant j-q antlneoplastic properties than either blocking the uptake of thymidine or the inhibition of the conversion of cytidlne diphosphate to deoxycytidine diphosphate. Ara-C rapidly kills S phase cells. It affects the passage rate of cells from S to G2 phase more than from Gl to Sl5. 

Kessel, D., T. C. Hall, and I. Wodinsky Transport and phosphorylation as factors in the antitumor action of cytosine arabinoside. Science 156, 1240 (1967). 

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