Differential metabolism of allopurinol and derivatives in Trypanosoma rangeli and T. cruzi culture forms.
We have compared the metabolism of allopurinol (4-hydroxypyrazolo (3,4-d)pyrimidine; HPP), by Trypanosoma rangeli, a non-pathogenic American trypanosome, and T. cruzi, the causative agent of Chagas' disease. Our results indicate that T. rangeli was unable to animate allopurinol mononucleotide to 4-aminopyrazolopyrimidine (APP) mononucleotide. Radioactivity was located in the RNA, but not the DNA, only of T. cruzi. Substrate specificity studies showed T. cruzi succino-AMP synthetase activity being 100-fold more active on HPP mononucleotide than the T. rangeli enzyme. These results possibly explain the fact that in conventional LIT medium T. rangeli growth was resistant to high concentrations of HPP. However the incubation of this hemoflagellate in an adenine-depleted LIT medium rendered it sensitive to low concentrations of APP, while remaining resistant to HPP. In contrast, and independently of the culture medium used, T. cruzi was extremely sensitive to both pyrazolopyrimidines.
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000265:Adenylosuccinate Synthase / Q000378:metabolism; D000493:Allopurinol / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D012313:RNA / Q000378:metabolism; D014345:Trypanosoma / Q000187:drug effects / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000378:metabolism*
C004420:4-aminopyrazolo(3,4-d)pyrimidine; D012313:RNA; D000493:Allopurinol; D000265:Adenylosuccinate Synthase; D000225:Adenine