Trypanosoma brucei: a survey of pyrimidine transport activities.

Abstract:

:Purine uptake has been studied in many protozoan parasites in the last few years, and several of the purine transporters have been cloned. In contrast, very little is known about the salvage of preformed pyrimidines by protozoa, and no pyrimidine transporters have been cloned, yet chemotherapy based on pyrimidine nucleobases and nucleosides has been as effective as purine antimetabolites in the treatment of infectious and neoplastic disease. Here, we surveyed the presence of pyrimidine transporters in Trypanosoma brucei brucei. We could not detect any mediated uptake of thymine, thymidine or cytidine, but identified a very high-affinity transporter for cytosine, designated C1, with a K(m) value of 0.048+/-0.009 microM. We also confirmed the presence of the previously reported U1 uracil transporter and found it capable of mediating uridine uptake as well, with a K(m) of 33+/-5 microM. A higher-affinity U2 uridine transporter (K(m)=4.1+/-2.1 microM) was also identified, but efficiency of the C1 and U2-mediated transport was low. Pyrimidine antimetabolites were tested as potential trypanocidal agents and only 5-fluorouracil was found to be effective. This drug was efficiently taken up by bloodstream forms of T. b. brucei.

journal_name

Exp Parasitol

authors

Gudin S,Quashie NB,Candlish D,Al-Salabi MI,Jarvis SM,Ranford-Cartwright LC,de Koning HP

doi

10.1016/j.exppara.2006.02.018

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

118-25

issue

2

eissn

0014-4894

issn

1090-2449

pii

S0014-4894(06)00064-6

journal_volume

114

pub_type

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