Pterin transport and metabolism in Leishmania and related trypanosomatid parasites.
The folate metabolic pathway has been exploited successfully for the development of antimicrobial and antineoplasic agents. Inhibitors of this pathway, however, are not useful against Leishmania and other trypanosomatids. Work on the mechanism of methotrexate resistance in Leishmania has dramatically increased our understanding of folate and pterin metabolism in this organism. The metabolic and cellular functions of the reduced form of folates and pterins are beginning to be established and this work has led to several unexpected findings. Moreover, the currently ongoing sequencing efforts on trypanosomatid genomes are suggesting the presence of several gene products that are likely to require folates and pterins. A number of the properties of folate and pterin metabolism are unique suggesting that these pathways are valid and worthwhile targets for drug development.
Ouellette
Marc
M
Centre de recherche en Infectiologie du CHUL, 2705, boul. Laurier, QC, Sainte-Foy, Canada GIV 4G2. marc.oulette@crchul.ulaval.edu
Drummelsmith
Jolyne
J
El-Fadili
Amal
A
Kündig
Christoph
C
Richard
Dave
D
Roy
Gaétan
G
D000818:Animals; D001692:Biological Transport; D005492:Folic Acid / Q000378:metabolism*; D007891:Leishmania / Q000378:metabolism*; D011622:Pterins / Q000378:metabolism*; D014351:Trypanosomatina / Q000378:metabolism*
D011622:Pterins; D005492:Folic Acid