Pyrimidines

P. Köhler

Most parasitic protozoa and all helminths are capable of synthesizing pyrimidine nucleotides via the de novo route. This pathway resembles that in higher eukaryotes, although some of the enzymes catalyzing the six sequential steps involved in the formation of uridine monophosphate (UMP) possess quite special features. An example is the protozoan dihydroorotate dehydrogenase that catalyzes the conversion of dihydroorotate to orotate in the rate-limiting fourth step of pyrimidine biosynthesis. Some properties of this enzyme differ from its mammalian counterpart considering it as a potential therapeutic target. Parasitic protozoa have also the capacity for pyrimidine salvage and can incorporate exogenous pyrimidine bases via a range of enzymes, including phosphoribosyltransferases (PRTases), nucleoside phosphorylases and kinases, respectively. Apicomplexans, however, are an exception in that these parasites lack the ability to scavenge preformed pyrimidines and, therefore, rely...