Document Detail


Differential effects of inhibitors of purine metabolism on two trichomonad species.
MedLine Citation:
PMID:  6608946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tritrichomonas foetus and Trichomonas vaginalis are both incapable of de novo purine nucleotide synthesis. Previous studies indicated that T. foetus relies mainly on the salvage of hypoxanthine and subsequent conversion of IMP to AMP and GMP, whereas T. vaginalis depends on direct conversions of exogenous adenosine to AMP and guanosine to GMP without much interconversion between the two nucleotides. These two different types of purine salvage suggest the possibility of differential sensitivities between the two species of trichomonad flagellates toward different purine antimetabolites. Mycophenolic acid, hadacidin, 8-azaguanine, and formycin B inhibited the growth of T. foetus but had no effect on T. vaginalis. Mycophenolic acid acted by blocking conversion of IMP to GMP, hadacidin inhibited conversion of IMP to AMP, and 8-azaguanine was incorporated into the T. foetus nucleotide pool, likely via hypoxanthine phosphoribosyl transferase. Formycin B was converted to 5'-monophosphate in T. foetus and inhibited the conversion of IMP to AMP. Its precise mechanism of action on T. foetus remains, however, to be elucidated. Alanosine, whose ribonucleotide derivative is a potent inhibitor of adenylosuccinate synthetase, had no effect on the growth or hypoxanthine incorporation in T. foetus, which may be due to the lack of conversion of alanosine to the ribonucleotide because of the absence of de novo purine nucleotide synthesis in parasites. Four adenosine analogs, adenine arabinoside, tubercidin, sangivamycin, and toyocamycin, were found inhibitory to the growth of T. vaginalis but showed little effect on T. foetus growth. Further investigations suggested that these four compounds acted on T. vaginalis by blocking incorporation of adenosine into the adenine nucleotide pool.
Authors:
C C Wang; R Verham; H W Cheng; A Rice; A L Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  33     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1984 Apr 
Date Detail:
Created Date:  1984-05-22     Completed Date:  1984-05-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1323-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alanine / analogs & derivatives,  pharmacology
Animals
Chromatography, High Pressure Liquid
Formycins / pharmacology
Glycine / analogs & derivatives,  pharmacology
Mycophenolic Acid / pharmacology
Purine Nucleotides / biosynthesis
Purines / metabolism*
Pyrimidine Nucleosides / pharmacology
Species Specificity
Toyocamycin / pharmacology
Trichomonas vaginalis / drug effects,  growth & development,  metabolism
Tritrichomonas / drug effects*,  growth & development,  metabolism
Tubercidin / pharmacology
Vidarabine / pharmacology
Grant Support
ID/Acronym/Agency:
AI-19391/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Formycins; 0/Purine Nucleotides; 0/Purines; 0/Pyrimidine Nucleosides; 13877-76-4/formycin B; 18417-89-5/sangivamycin; 24280-93-1/Mycophenolic Acid; 5536-17-4/Vidarabine; 56-40-6/Glycine; 56-41-7/Alanine; 5854-93-3/alanosine; 606-58-6/Toyocamycin; 689-13-4/hadacidin; 69-33-0/Tubercidin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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