Pyrimidine Phosphotransferases

FIG. 6.13 Mammalian pyrimidine salvage and interconversion pathways. Enzymes listed in Figs 6.13-6.17 are as follows (1) deoxyCMP deaminase (2) thymidylate synthase (3) ribonucleotide reductase (4) deoxyuridine triphosphatase (5) CTP synthetase (6) nucleotide kinase (7) deoxyTMP kinase (8) nucleotide diphosphokinase (9) non-specific phosphatase or nucleotidase (10) cytidine kinase (11) pyrimidine phos-phorylase or hydrolase (12) uracil PRTase (13) cytidine deaminase (14) thymidine kinase (15) cytidine phosphotransferase (16) uridine phosphotransferase (17) thymidine phosphotransferase (18) deoxyribo-nucleotide phosphotransferase (19) cytosine PRTase. 

Consistent with the metabolic data, there is no dihydrofolate reductase/thymidylate synthase activity (75). Thymidine is salvaged by a phosphotransferase. Uracil PRTase, uridine phosphorylase, cytidine deaminase and uridine and cytidine phosphotransferases were found. The major pyrimidine salvaged is uracil via its PRTase. The lack of incorporation of salvaged uracil into DNA and the lack of thymidylate synthase indicates that this parasite cannot synthesize TMP from UMP. It is dependent on salvage for its thymidine requirements. This parasite possesses a hydroxyurea-resistant ribonucleotide reductase and can synthesize deoxycytidine nucleotides from cytidine nucleotides. 

The salvage activities of T. foetus and T. vaginalis also differ (22,77). Unlike T. foetus, the level of uracil PRTase activity is very low. Uracil is converted into uridine by a uridine phosphorylase uridine is then phosphorylated by a uridine phosphotransferase to UMP (Fig. 6.15). Cytidine and thymidine also are converted into their nucleotide monophosphates by phosphotransferase activities. There is no detectable pyrimidine nucleoside kinase activity and the only significant interconversion among salvaged pyrimidines is catalyzed by cytidine deaminase to form uridine. 

This parasite also differs from T. foetus in that it lacks nucleotide reductase activity. Pyrimidine deoxynucleotides are obtained by salvage of deoxynucleosides by the deoxyribonucleoside phosphotransferase which acts not only on pyrimidine but also purine deoxyribonucleosides (22). 

Saivage enzymes Nucleoside phosphotransferases involved in the salvage of purines and pyrimidines in protozoans... 

Potentially deleterious side reactions are avoided. The enzyme itself might be damaged by light if it could be activated by light in the absence of bound DNA harboring a pyrimidine dimer. The DNA-induced absorption band is reminiscent of the glucose-induced activation of the phosphotransferase activity of hexokinase. 

Phosphodiesterases, phosphatases, 5 -nucleotidases, 3 -nucleotidases and phosphotransferases have been discussed in the section on purine breakdown. Some of these enzymes also act on pyrimidine nucleotides, yielding either the nucleoside or the free base. Cytosine deaminases have been found in yeast and E. coli. Cyti-dine and cytidylic acid deaminases are present in extract of most mammalian tissue. The properties of these enzymes are still poorly understood. 

Similar presentation/laboratory findings but different derangement in pyrimidine nucleotides found in a putative disorder CDP-choline phosphotransferase deficiency. 

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