Deoxycytidylate deamination

Before they can be degraded, cytidine and deoxycytidine are converted to uridine and deoxyuridine, respectively, by deamination reactions catalyzed by cytidine deaminase. Similarly, deoxycytidylate (dCMP) is deaminated to form deoxyuridylate (dUMP). The latter molecule is then converted to deoxyuridine by 5 -nucleotidase. Uridine and deoxyuridine are then further degraded by nucleoside... 

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. 

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). 

Deoxycytidylate deaminase was first isolated from sea urchin e s by Scarano and has since been demonstrated in many animal tissues the deaminases from spleen and chick embryo have been partly purified (23, 24). The enzyme requires that the substrate must be a 4-aminopyrimidine deoxyribonucleoside 5 -monophosphate, and will accept the following substituents at the pyrimidine 5-position methyl, hydroxymethyl, fluoro, iodo, and bromo. Notably, the following are not deaminated cytidine, deoxycytidine, eytidylate, dCDP, and dCTP. The concentration of this enzyme in cells appears to be related to their proliferative state in that the enzyme is found in growing tissues, but activities are low in adult tissues such as liver. 

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 ... 

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