Figure 1 | Leukemia

Figure 1

From: Nucleoside analogues: mechanisms of drug resistance and reversal strategies

Figure 1

Representation of the metabolism and drug target interactions of deoxynucleoside analogues in proliferating cells (NA). NA enters cells via specific nucleoside transporters. Once inside the cell, NA are phosphorylated by deoxycytidine kinase (DCK), NMPK and NDPK to the active 5′-triphosphate derivatives. NA catabolism can result from rapid deamination by cytidine deaminase to non-toxic metabolites. Cytoplasmic 5′-nucleotidase (5′Nucl) activity opposes that of DCK by dephosphorylating 5′-monophosphate derivatives, thereby preventing the production of the active form. NA exerts their action by incorporation into newly synthesized DNA resulting in chain termination and cell death. Also, some NA indirectly block DNA replication by inhibiting ribonucleotide reductase (RR) enzyme, that in turn inhibit reduction of ribonucleotides diphosphate (NDPs) to deoxyribonucleotides diphosphate (dNDPs). The decrease of deoxyribonucleotides triphosphate (dNTPs) pools favors incorporation of NA active 5′-triphosphate derivatives into DNA.

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