6 - Purine and Pyrimidine Metabolism

Abstract

This chapter discusses the metabolism of purine and pyrimidine nucleotides in parasitic protozoa and helminths. They are the monomeric units of both DNA and RNA; ATP serves as the universal cellular energy source, adenine nucleotides are components of three key coenzymes (NAD+, FAD and CoA), they are used to form activated intermediates, such as uridine-diphosphate glucose, and they serve as metabolic regulators. The results of studies by investigators show that purine metabolism in these pathogens differs from that of their mammalian hosts. Whereas mammalian cells synthesize the purine ring de novo from simple precursors, all the parasitic protozoa and helminths that have been investigated lack de novo purine synthesis and utilize preformed purines obtained from their host environment. These pathogens use various purine salvage pathways to supply their purine nucleotide requirements. The chapter explains that the difference in purine metabolism between host and parasite is an area of potential chemotherapeutic intervention that is actively being explored. Unlike purines, pyrimidine metabolism,with the exception of the amitochondrial protists Giardia lamblia, Trichomonas vaginalis and Tritrichomonas foetus, is similar to mammalian cells, all pathogenic protozoa and helminths are able to synthesize pyrimidines de novo. Like mammalian cells, their ability to salvage pyrimidines is limited when compared to purine salvage. The chapter summarizes that with the exception of G.lamblia and T.vaginallis, all the parasitic organisms discussed in the chapter possess ribonucleotide reductase and can synthesize purine deoxynucleotides based on one or more of the following criteria: organisms multiply in the absence of deoxynucleosides, reductase activity can be detected in cell extracts, bases or ribonucleosides are incorporated into DNA or organisms are sensitive to growth inhibition by hyroxyurea (a ribonuleotide reductase inhibitor).