Sodium Stibogluconate (Pentostam) Inhibition of Glucose Catabolism via the Glycolytic Pathway, and Fatty Acid Beta-Oxidation in Leishmania mexicana Amastigotes.

摘要

The biochemical mechanism of action of antimony (Sb) in pentavalent form complexed to gluconic acid (sodium stibogluconate)-the drug of choice for the leishmaniases-has been only slightly investigated. We recently reported that, in stibogluconate-exposed Leishmania mexicana amastigotes, there is a dose-dependent decrease in the ATP/ADP ratio. To investigate mechanisms by which ADP phosphorylation to ATP might be inhibited, stibogluconate-exposed amastigotes were incubated with carbon 14 glucose, fatty acid, or acetate, and carbon dioxide production was determined. In organisms exposed to 500 micrograms antimony/ml, formation of carbon dioxide 14 from (6-carbon 14 from (1-carbon 14) glucose and (2-carbon 14) acetate was inhibited <15%. These results suggest that glucose catabolism via glycolytic enzymes and fatty acid beta-oxidation, but not glucose metabolism via the hexosemonophosphate shunt or the citric acid cycle, is specifically inhibited in stibogluconate-exposed Leishmania mexicana amastigotes. Inhibition of these pathways suggest a mechanism for the inhibition of ADP phosphorylation previously reported. Reprints.