Uptake of the trypanocidal drug suramin by bloodstream forms of Trypanosoma brucei and its effect on respiration and growth rate in vivo
Abstract
After a single intravenous injection of suramin the rate of removal of the drug from the plasma into other tissue compartments of the rat is independent of initial concentration. The data can be fitted to the sum of two exponential functions, consistent with a two-compartment, open model system. Trypanosomes take up only small amounts of suramin in vivo and do not actively concentrate the drug within the cell. Uptake is apparently by a non-saturable process that decreases with time and is dependent on the amount of suramin already taken up. Once within the cell, suramin progressively inhibits respiration and glycolysis, such that, for a given exposure in vivo, inhibition of oxygen consumption is proportional to the total amount of suramin absorbed. It can be calculated that only a fraction (4--9%) of this total is required to inhibit respiration to the extent found in broken cell preparations. The combined inhibition of two key enzymes in glycolysis--the sn-glycerol-3-phosphate oxidase (EC unassigned) and the glycerol-3-phosphate dehydrogenase (NAD+) (sn-glycerol-3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8)--are sufficient to account for the differential inhibition of glucose and oxygen consumption and of pyruvate production...Continue Reading
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In vitro susceptibilities of Plasmodium falciparum to compounds which inhibit nucleotide metabolism.
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