Nucleic Acid Metabolism in Trichomonas vaginalis
It has been noted that all parasitic protozoa examined to date are unable to synthesize purine rings de novo. The studies on Trypanosoma cruzi 1 Leishmania braziliensis,2 Plasmodium lo-phurae,3 Trypanosoma mega,4 and Eimeria ten-ella 5 have provided well-documented cases of the lack of de novo purine nucleotide synthesis and hence the dependence of these organisms on purine salvage for survival. Some of the purine salvage enzymes in these parasites have also acquired unique properties differing from those of the host. For instance, allopurinol, a hypo-xanthine analog unimportant in the metabolism of mammalian cells, is apparently converted by hypoxanthine phosphoribosyltransferase (HPRT) in the parasites to the corresponding nucleotide and is eventually incorporated into the parasite RNA.6 These biochemical events seem to have rendered allopurinol active against Leishmania,2 African trypanosomes,7 T. cruzi,8 and E. tenella.5 Similar conversions of the purine nucleoside analogs, such as allopurinol riboside,9 formycin B,10 and 9-deazaino-sine,11 to their nucleotides have also made these compounds effective antileishmanial and antitrypanosomal agents. The purine salvage enzymes in the parasitic protozoa thus not only serve essential biologic functions, but also possess sufficiently broad substrate specificities to become potential targets for antiparasitic chemotherapy.
KeywordsHigh Performance Liquid Chromatography Purine Nucleotide Nucleic Acid Metabolism Giardia Lamblia Adenosine Kinase
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- 1.Berens RL, Marr J J, LaFon SW, Nelson DJ: Purine metabolism in Trypanosma cruzi. Mol Biochem Parasitol 3:187–196, 1981.Google Scholar
- 2.Marr J J, Berens RL: Antileishmanial effect of allopurinol. II. Relationship of adenine metabolism in Leishmania spp. to the action of allopurinol. J Infect Dis 136:724–732, 1977.Google Scholar
- 3.Walsh CJ, Sherman IW: Purine and pyrimidine synthesis by the avian malaria parasite, Plasmodium lophurae. J Protozool 15:763–770, 1968.Google Scholar
- 6.Marr J J, Berens RL, Nelson DJ: Antitrypanosomal effects of allopurinol: Conversion in vitro to aminopyrazolopyrimidine nucleotides by Trypanosoma cruzi. Science 201:1018–1020, 1978.Google Scholar
- 7.Berens RL, Marr J J, Brun R: Pyrazolopyrimidine metabolism in African trypanosomes: Metabolism similarities to Trypanosoma cruzi. Mol Biochem Parasitol 3:187–196, 1981.Google Scholar
- 11.Marr J J, Berens RL, Cohn NK, Nelson DJ, Klein RS: Biological action of inosine analogs in Leishmania and Trypanosoma spp. Antimicrob Agents Chemother 25:292–295, 1984.Google Scholar
- 12.Honigberg BM: Trichomonads of veterinary importance. In Kreier JP (ed): Parasitic Protozoa, vol 2, pp 164–275. New York: Academic Press, 1978.Google Scholar