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pyrimidine deoxyribonucleotide phosphorylation

General Background Deoxyribonucleotides are synthesised de novo at the diphosphate level through reduction of the 2?-hydroxyl group of the corresponding ribonucleotides (see |FRAME: PWY-7184|). This reduction is mediated by the key enzyme |FRAME: EC-1.17.4.1 "ribonucleoside-diphosphate reductase"|. The de novo synthesis of ribonucleotides is very expensive, and organisms have adapted to salvage potential precursors from their environment. Since nucleotides can not be imported into the cell due to the negative charge of the phosphate groups, salvage is limited to free bases and nucleosides. Salvage is very important for many types of organisms and cells. It has been shown that in quiescent or terminally differentiated mammalian cells, resting in the G0 phase, ribonucleotide reductase is not produced due to a block during transcription and the cells rely on salvage for deoxyribonucleotides for DNA repair |CITS: [3044582][1696835]|. Similarly, the salvage pathway is the sole provider of deoxyribonucleotides to be used in DNA repair or mitochondrial DNA replication in G1 cells. Studies with the plant |FRAME: TAX-3702| showed that uracil salvage is necessary for early development |CITS: [19563437]| and that uridine salvage plays a crucial role in photoassimilate allocation and partioning |CITS: [21828290]|. The deoxyribonucleosides enter through the cell membrane by facilitated diffusion via a low affinity, high capacity, non-concentrative nucleoside carrier protein with a wide specificity, possessed by almost all animal cells |CITS: [3048401]|. The next step in the salvage pathway is the phosphorylation of the nucleosides to monophosphates. Once phosphorylation occurs, the nucleotides are trapped intracellularly due to their negative charge. About This Pathway As shown in the pathway |FRAME: PWY-7199|, the deoxyribonucleosides are imported into the cell and phosphorylated by deoxyribonucleoside kinases at the 5' position. The monophosphates are then phosphorylated further to form the triphosphates that are required for DNA synthesis, as described in this pathway. |FRAME: TMP| is phosphorylated to the diphosphate form by a specific |FRAME: EC-2.7.4.9 "dTMP kinase (EC 2.7.4.9)"|, while |FRAME: DCMP| is phosphorylated in eukaryotes by the |FRAME: EC-2.7.4.14 "bifunctional UMP/CMP kinase (EC 2.7.4.14)"| and in prokaryotes by a dedicated |FRAME: EC-2.7.4.25 "(d)CMP kinase (EC 2.7.4.25)"|. Both diphosphates, |FRAME: DUDP| and |FRAME: DCDP|, are phosphorylated to the triphosphate forms by the broad-substrate range |FRAME: EC-2.7.4.6 "nucleoside-diphosphate kinase (EC 2.7.4.6)"|.

from BIOCYC source record: META_PWY-7197
Type: pathway
Taxonomic scope
:
conserved biosystem
BSID:
907959

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