Deoxynucleotides

P. Köhler

Deoxyribonucleotides, the building blocks of DNA, are derived in most parasitic protozoa and in helminths, as in mammalian cells, primarily from the corresponding ribonucleotides as catalyzed by ribonucleotide reductase. Some protozoa, including Entamoeba, Giardia, and Trichomonas vaginalis , lack ribonucleotide reductase and, thus, have to meet their deoxynucleotide requirements by salvage pathways. The synthesis of deoxythymidine nucleotides, which are required for DNA synthesis, is initiated by the conversion of dUMP to dTMP (Fig. 1). In this process, the necessary methylation of the pyrimidine ring is catalyzed by the tetrahydrofolate-dependent enzyme thymidylate synthase (TS). In several protozoan species, including the apicomplexans, Leihmania major and Trypanosoma cruzi, TS is unusual in that it differs in its structural and kinetic properties from the corresponding mammalian enzyme and exists as a bifunctional protein associated with dihydrofolate reductase (DHFR)...