Mode of anticoccidal action of arprinocid

Wang, Ching C.; Simashkevich, Paula M.; Stotish, Ronald L.

doi:10.1016/0006-2952(79)90685-3

Cited by 22 publications

(2 citation statements)

References 39 publications

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“…The selective inhibition by bredinin, an inhibitor of IMP dehydrogenase, of GMP formation from hypoxanthine in Plasmodium falciparum [86], provides good evidence for the existence in this parasite of IMP dehydrogenase and a further indication that hypoxanthine is a major source of purines for it. Eimeria tenella growing in tissue culture cells is sensitive to arprinocid, it is thought that the toxicity is due to the compound inhibiting IMP dehydrogenase and hence the conversion of IMP to GMP [87]. Recently, Hupe et al [88] have suggested that the IMP dehydrogenase from E. tenella is a valuable chemotherapeutic target enzyme, and have reported that it is specifically inhibited by mycophenolic acid; this compound was found to be inhibitory to the growth of the parasite in tissue culture.…”

Section: Purine Nucleotide Interconversionsmentioning

confidence: 99%

Purine and pyrimidine metabolism in parasitic protozoa

Hassan¹

1988

FEMS Microbiology Letters

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Section: Purine Nucleotide Interconversionsmentioning

confidence: 99%

Purine and pyrimidine metabolism in parasitic protozoa

Hassan¹

1988

FEMS Microbiology Letters

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“…But wild-type and mutant T. gondii grown in cell culture are equally efficiently labeled by [3H]adenosine (12), suggesting that adenosine kinase does not play a major role in salvaging purines for the parasite. One other species of coccidia Eimenria tenella, which develops inside the caecal epithelial cells ofchickens, effectively takes up hypoxanthine and preferentially incorporates label from it into nucleic acids when grown in cell culture (13,14). Purine metabolism in this parasite is particularly interesting in view of the uricotelic metabolism of chickens and the high levels of hypoxanthine known to accumulate in avian tissues (15).…”

mentioning

confidence: 99%

Purine metabolism in the protozoan parasite Eimeria tenella.

Wang¹,

Simashkevich²

1981

Proc. Natl. Acad. Sci. U.S.A.

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Crude extracts of the oocysts of Eimeria tenella, a protozoan parasite of the coccidium family that develops inside the caecal epithelial cells of infected chickens, do not incorporate glycine or formate into purine nucleotides; this suggests lack of capability for de novo purine synthesis by the parasite. The extracts, however, contain high levels of activity of the purine salvage enzymes: hypoxanthine, guanine, xanthine, and adenine phosphoribosyltransferases and adenosine kinase. The absence of AMP deaminase from the parasite indicates that E. tenella cannot convert AMP to GMP; the latter thus has to be supplied by the hypoxanthine, xanthine, or guanine phosphoribosyltransferase of the parasite. These three activities are associated with one enzyme (HXGPRTase), which has been purified to near homogeneity in high yield (71-80%) in a single step by GMP-agarose affinity column chromatography. The size ofthe enzyme subunit is estimated to be 23,000 daltons by NaDodSO4 gel electrophoresis. Kinetic studies suggest differences in purine substrate specificity between E. teneUa HXGPRTase and chicken liver HGPRTase. Allopurinol preferentially inhibits the parasite enzyme by competing with hypoxanthine; a 1K 22 ,AM. All parasitic protozoa examined to date appear to be unable to synthesize the purine ring de novo, as reflected by the failure ofradiolabeled glycine and formate to label nucleic acid purines of the parasites in minimal defined media. Of particular note are studies on Trypanosoma cruzi (1), Leishmania braziliensis (2), Plasmodium lophurae (3), and Trypanosoma megna (4), which provide well-documented cases for lack of capability for de novo purine synthesis and, hence, dependence on purine salvage. Host hypoxanthine, adenine, and adenosine have been suggested as the three major sources of purines for these parasites (5), but recent evidence favors the hypothesis that hypoxanthine may be the main, if not the only, supply of purines to Plasmodia (6, 7), Leishmania (2,8), and Crithidiafasciculata (8). Adenosine and adenine are probably converted to hypoxanthine by the purine nucleoside hydrolase (9) and adenine aminohydrolase (2) ofthe parasites before incorporation into the nucleotide pool.Among members of the coccidia family, a group of parasitic protozoa developing inside intestinal epithelial or muscle cells ofinfected animals, Toxoplasma gondii trophozoites were found incapable of incorporating glycine or formate into their DNA (10). They grow normally inside cultured Lesch-Nyhan skin fibroblasts, which lack hypoxanthine-guanine phosphoribosyltransferase (HGPRTase), and effectively incorporate exogenous hypoxanthine and guanine into nucleic acids (11). T. gondii has no detectable adenine phosphoribosyltransferase (APRTase) but has a high level ofadenosine kinase (12). The latter activity is largely lost in a mutant resistant to 1-,B3D-arabinofuranosyladenine (AraA). But wild-type and mutant T. gondii grown in cell culture are equally efficiently labeled by [3H]adenosine (12), suggesting that adenos...

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Anticoccidial Drugs and Vaccines

Conway¹,

McKenzie²

2007

Poultry Coccidiosis

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Mode of anticoccidal action of arprinocid

Cited by 22 publications

References 39 publications

Purine and pyrimidine metabolism in parasitic protozoa

Purine and pyrimidine metabolism in parasitic protozoa

Purine metabolism in the protozoan parasite Eimeria tenella.

Anticoccidial Drugs and Vaccines

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