ALTERNATE PATHWAYS OF PURINE METABOLISM IN SOME AFRICAN TRYPANOSOMES
ALTERNATE PATHWAYS OF PURINE METABOLISM IN SOME AFRICAN TRYPANOSOMES
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Date
1983-10
Authors
PATRICK, OKAFOR JAMES OGUNUDE
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Abstract
The alternate pathways of purine metabolism in Tradeswoman
Congolese; T. vivas and T. Bruce were investigated. Enzymes
of purine salvage pathway were detected in the trypanosomes
although there were differences in activity. Purine nucleotide
hydro lase was found in the gastronomes but purine nucleotide
phosphorylate was found only in T. conqol^nse. Adenine
microhydrodynamics, an enzyme usually associated with bacteria was
detected in T. viva x. The gastronomes studied lack adenine
dreaminess but adenine mono-phosphate dreaminess was detected
in T. Brucie and T. Congolese. Dreaminess provide points at
which interconversion of purines occur; thus differences exist
at the level of metabolic interconversion points. A proposal
for the salvage of purines in these gastronomes is presented.
Transport of purines in T. ambivalence and T. Congolese,
measured as uptake of trialed adenine was shown to take place
by mediated mechanism. Two transport loci, one transporting
adenine and guano-sine, and the other transporting thymine
was demonstrated. The inhibitors of nucleotide transport in
animal cells, nitrobenzylthioinosine and pyrimidine, did not
Inhibit the uptake of adenine by T. ambient.
Nitrobenyylthioinosine which also binds tightly to cells did
not bind to either T. gambiense or T. congoiense.
v.
efflux of 3H--thymidine from erythrocytes was used to
measure damage to erythrocyte membrane in control mice and
mice infected with trypanosomes. The efflux in infected mice
was higher than in the controls. Since erythrocytes have a
high rate of purine turnover, this may be a major source of
exogenous purines for the trypanosomes.
The toxicity to mice and rats and trypanocidal activity
of the tubercidin was confirmed by the present study. The
toxicity of tubercidin was alleviated by intraperitoneal
injection of nitrobenzylthioinosinate (5mkj/kg) 5 minutes
earlier. Nitrobenzylthioinosinate neither had acute toxic
nor trypanocidal effect at the doses tested and did not
interfere with the trypanocidal effect of tubercidin. It
is suggested that this nucleotide inhibitor. nitrobenzylthioinosinate,
should be evaluated in combination with declension
analogues in the therapy of African trypanosomiasis.
Description
A thesis submitted to the Postgraduate School,
Ahmadu Bello University, in partial fulfillment
of the requirements for the degree of
DOCTOR OF PHILOSOPHY
Department of : BIOCHEMISTRY
Faculty of : SCIENCE
Ahmadu Bello University, Zaria.
Dates October, 1983
Keywords
ALTERNATE,, PATHWAYS,, PURINE,, METABOLISM,, SOME AFRICAN,, TRYPANOSOMES