Abstract
The parasite Trypanosoma cruzi metabolizes allopurinol by a sequential conversion to allopurinol mononucleotide and aminopurinol mononucleotide. The latter is incorporated into RNA. This transformation of a widely used innocuous agent, allopurinol, into a toxic adenine analog appears to account for the antiprotozoan effect of allopurinol. These unique enzymatic activities appear to occur only in T. cruzi and the pathogenic lesihaminae. Allopurinol may serve as a model for the synthesis of similar antiprotozoan agents.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenine / pharmacology
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Allopurinol / antagonists & inhibitors
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Allopurinol / metabolism
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Allopurinol / pharmacology*
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Animals
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Pyrimidine Nucleotides / antagonists & inhibitors
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Pyrimidine Nucleotides / biosynthesis*
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Pyrimidine Nucleotides / pharmacology
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Ribonucleotides / antagonists & inhibitors
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Ribonucleotides / biosynthesis
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Ribonucleotides / pharmacology
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Trypanocidal Agents / antagonists & inhibitors
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Trypanocidal Agents / metabolism*
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Trypanocidal Agents / pharmacology
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Trypanosoma cruzi / drug effects
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Trypanosoma cruzi / growth & development
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Trypanosoma cruzi / metabolism*
Substances
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Pyrimidine Nucleotides
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Ribonucleotides
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Trypanocidal Agents
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Allopurinol
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Adenine