Deoxycytidine phosphates

UMP is the parent compound in the synthesis of cytidine and deoxycytidine phosphates and thymidine nucleotides (which are deoxyribonucleotides). 

The deoxycytidine phosphates result from reduction of CDP to dCDP by a mechanism analogous to that described for the purine nucleotides. Then dCDP is converted to dCTP by nucleoside diphosphate kinase. 

Metabolism of the pyrimidine deoxyribonucleotides is more complex because, in addition to transfer of phosphoryl groups, deamination and methylation reactions occur at this level. Specifically, the thymidine phosphates are derived by methylation of deoxyuridylate, and the latter may be derived from the deoxycytidine phosphates by way of deoxycytidylate deaminase. The deoxycytidine phosphates are not formed by amination of deoxyuridine phosphates, but are derived entirely from the cytidine phosphates by enzymatic reduction (Chapter 16). 

F. From Deoxycytidine Phosphates in Phage-Infected Bacteria.. 237... 

The ribonucleotide reductases form deoxycytidine phosphates which are destined for incorporation into DNA these nucleotides are diverted to some extent into the deoxyuridylate pool, and thence into the thymine nucleotides, through the action of deoxycytidylate deaminase. This diversionary flow into the thymine pathway is regulated by the demand for the terminal products, dTTP and dCTP the valve controlling this flow is deoxycytidylate deaminase, the activity of which is subject to allosteric regulation by dTTP and dCTP. 

Deoxycytidylate deaminase is evidently absent from a number of bacterial species, includii E. coli, S. typhimvrium, and B. subtilts. Accordingly, in these cells the deoxycytidine phosphates do not contribute to the synthesis of the thymidine phosphates in the manner described above for animal cells. However, enzymes catalyzing the deamination of dCTP have been demonstrated in E. ccU and S. typhimvrium the latter enzyme has been partly purified and shown to deaminate dCTP, but not CTP, dCDP, CDP, eytidylate, nor deoxycytidine (26). The formation of dUTP by this enzyme, followed by the action of the specific dUTP pyrophosphatase, would consitutue a route for the formation of deoxyuridylate ... 

The work of Karlstrom and Larsson 26), discussed in Chapter 14 (see Table 14-11), illustrates the functioning of this route. Karlstrdm and Larsson showed that a pyrimidine-requiring E. coli mutant (OK305), which was also deficient in deaminase activities for cytidine and deoxycyti-dine, synthesized DNA thymidylate from cytidine in a way which primarily involved the deoxycytidine phosphates. It is seen in Table 14r-II that the labeling pattern of DNA thymidylate resembled that of DNA deoxycytidy-late and was very different from that of RNA uridylate. Conversion of most of the incorporated cytidine to deoxyuridylate (and thence to the thymidine phosphates) by a route which did not involve uridine phosphates would appear to explain these data 27) ... 

The cytotoxic activities of the 2, 2 -difluoro analog (775) of 737 against Chinese hamster ovary and tumor cells, in comparison with those of 1- -d-arabinofuranosylcytosine ara-C, a drug for leukemia), have been studied 775 is transported the faster through membrane into cells, more effectively phosphorylated by the deoxycytidine kinase (to the 5 -mono-phosphate) and, after conversion into the 5 -triphosphate, more highly accumulated in the cells, with longer duration time, than is ara-C, but nevertheless 775 is incorporated into the DNA to a lesser extent than is ara-C. These characteristics of 775 were discussed. 

Cytosine Cytidine-5 -phosphate (CMP) Deoxycytidine-5 -phosphate (dCMP)... 

This enzyme [EC 2.7.1.74] catalyzes the reaction of a nucleoside triphosphate with deoxycytidine to produce a nucleoside diphosphate and dCMP. This enzyme can use any nucleoside triphosphate (except dCTP) as the phosphate-donor substrate and it can phosphorylate cytosine arabinoside as well. 

Hudarabine phosphate is a fluorinated nucleotide analog of the antiviral agent vidarabine. Its cytotoxicity is not well understood. It is rapidly dephospho-rylated at the cell membrane level and then rephos-phorylated intracellularly by deoxycytidine kinase to the active triphosphate derivative. It inhibits DNA polymerase and DNA primase. It is also incorporated into DNA and RNA. Hudarabine is administered intravenously by infusion over 30-120 min. It is eliminated by renal excretion with a terminal half life 10 hours. Adverse effects include myelosuppres-sion, nausea, vomiting, chills and fever. The number of CD4 positive cells is reduced and the incidence of opportunistic infections is increased. 

In contrast to the radical A generated from the cytidine phosphate (Fig. 29), the radical A formed from the 2 -fluoromethylene-2-deoxycytidine cannot eliminate a water molecule (Fig. 32). Instead, it undergoes an isomerisation into a new radical B centred on the fluorine-substituted carbon. The latter finally provides, after... 

Deoxycytidine 5 -phosphate C3dosine + deoxyribose + phosphate Nucleoside is 2 -deoxyc3ftidine, composed of c3dosine and deoxyribose... 

In a study of 2 -deoxycytidine 5 -phosphate monohydrate (5 -dCMP, compound III), the radicals found at 10 K and their fate on annealing to 77 K were investigated.13 The unirradiated molecule is protonated at N3 from the water of hydration. This study is a reinvestigation and update of a previous study of the same compound.14... 

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