Deoxycytidylate phosphates

DNA contains the bases adenine (A), thymine (T), guanine (G), and cytosine (C). These bases are covalently attached to the deoxyribose phosphate to form nucleotides. The respective nucleotides are called deoxyadenylic acid (dA), deox)hhy-midylic acid (dT), deoxyguanylic acid (dG), and deoxycytidylic add (dC). The prefix "deoxy" indicates that the sugar is deoxyribose, rather than ribose. The word "acid" indicates that the ribose contains a covalently bound phosphoric acid group. 

There is no evidence for the enzyme deamination of cytidine 5 -phosphates, although deoxycytidylate deaminase is a well known enzyme [118,119]. The direct conversion of cytidine compounds to uridine ones occurs by the deamination of cytidine or cytosine. 

Sugino el al. 17) have partly purified a deoxycytidylate kinase from calf thymus this preparation also phosphorylates cytidylate and uridylate, but not deoxyuridylate. The deoxyuridylate kinase activity was recovered in another protein fraction and so represents a distinct entity. As phosphate donors, only ATP and dATP were active in the cytidylate reaction. 

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). 

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 ... 

In experiments of this type with animal tissues, Rose and Schweigert (2) and Thomson et al. (S) showed that pyrimidine ribonucleosides were converted to DNA nucleotides without cleavage of the JNT-glycosidic bond. As well, Larsson and Neilands (4) performed a similar type of experiment in which P-phosphate and uniformly labeled C-cytidine were administered to rats with regenerating liver. Both substances were incorporated into the liver polynucleotides which, upon isolation, were degraded to their constituent nucleotides for analysis. Their data (Table 16-1) showed that the four nucleotides of RNA had similar specific activities with respect to P, indicating that the labeled phosphate readily equilibrated with the nucleoside phosphate pool during the experimental period. In this experiment, cytidylate derived from RNA and deoxycytidylate derived from DNA had the same P C ratio. This result indicated that both polynucleotide subunits, deoxycytidylate and cytidylate, were derived from a common precursor, evidently a ribonucleotide. 

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