Pyrimidine deoxyribonucleosides phosphorylation

Although cells derive their deoxyribonucleotides primarily by reduction of ribonucleotides, the deoxyribonucleosides can be utilized to some extent by way of kinase reactions. Phosphorylation of deoxyribonucleosides represents the only known point of entry into the sequences of deoxyribonucleotide metabolism other than the main entry point, ribonucleotide reduction. Pyrimidine deoxyribonucleosides may be incorporated into DNA in animal cells by this route. The conversion of deoxyadenosine and deoxyguanosine into deoxyribonucleotides and thence into DNA would also appear possible by a kinase-initiated sequence, because the enzymatic phosphorylation of these compounds has been demonstrated. However, this route has not been well studied in animal cells and its assessment is complicated by very active deamination and phosphorolytic cleavage reactions which compete with the reactions leading to DNA. E. coli cells appear to possess only one kinase capable of phosphorylating deoxyribonucleosides, thymidine kinase. 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

The purine (Pu or R for short) and pyrimidine (Py or Y for short) bases, are connected by a N-glycosidic linkage to the C-T of the pentose sugar, either a ribose in RNA or a 2 -deoxyribose in DNA. The base-(2 -deoxy)ribose unit is called a nucleoside (ribonucleoside or 2 -deoxyribonucleoside). When a nucleoside is phosphorylated either at the 3 -OH or 5 -OH, it is called 3 -nucleotide (Np) or S -nucleotide (pN), respectively. The number of phosphate groups, for example, at the 5 -OH of adenosine, determines whether the nucleotides are designated as adenosine 5 -wo ophosphate (AMP), adenosine 5 -diphosphate (ADP), and... 

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