Cytosine arabinoside (Ara-C) metabolism within cells.

Ara-C enters the cell mainly via (1) equilibrative nucleoside transporter 1 (hENT1). Inside the cell, Ara-C is phosphorylated to Ara-CMP by (2) deoxycytidine kinase (dCK). Subsequently, Ara-CMP is phosphorylated to its active form Ara-CTP. Incorporation of Ara-CTP into the DNA during DNA synthesis leads to programmed cell death or apoptosis. Ara-CTP formation can, however, be obstructed. (3) Pyrimidine nucleotidase I (PN-I) inhibits Ara-CTP formation by opposing the action of dCK. (4) Cytidine deaminase (CDA) and (5) deoxycytidylate deaminase (dCMPD) convert Ara-C to Ara-U and Ara-CMP to Ara-UMP, respectively, thereby decreasing the amount of Ara-CTP that can be formed.