The cytosolic salvage of precursors used to synthesize pyrimidine deoxyribonucleotides from the environment is an important alternative to the energetically expensive de novo synthesis pathway. Since the negative charge of the deoxyribonucleotide phosphate groups prevents their import into the cell, salvage is restricted to deoxyribonucleosides which are transported into the cell via facilitated diffusion by a nucleoside carrier protein. Following uptake into the cell, the deoxyribonucleosides are phosphorylated. Phosphorylation imparts negative charges to the compounds, effectively trapping them within the cell. After transport into the cell, 2'-deoxycytidine has two fates. The first route starts with the conversion of 2'-deoxycytidine into dCMP by deoxynucleoside kinase. This is followed by the conversion of dCMP into dCDP by UMP/CMP kinase, requiring a magnesium ion cofactor, and then the conversion of dCDP into dCTP by nucleoside-diphosphate kinase, requiring a magnesium ion cofactor. The second route starts with the conversion of 2'-deoxycytidine into 2'-deoxyuridine by cytidine deaminase, requiring a zinc ion cofactor. This is followed by the conversion of 2'-deoxyuridine into dUMP by thymidine kinase, and then the conversion of dUMP into dTMP by dihydrofolate reductase-thymidylate synthase. Alternatively, dTMP can be synthesized by thymidine kinase using thymidine transported into the cell by a nucleoside carrier protein. Next, thymidylate kinase converts dTMP into dTDP, and then nucleoside-diphosphate kinase, requiring a magnesium ion cofactor, converts dTDP into dTTP.

Pyrimidine Deoxyribonucleosides Salvage References