Effect of mitochondrial inhibitors on adenosinetriphosphate levels in Plasmodium falciparum.
1. The effects of mitochondrial inhibitors on the ATP levels of intraerythrocytic Plasmodium falciparum have been studied. 2. Changes in parasite ATP or ADP levels with time in response to various mitochondrial inhibitors appear quite complex; ATP levels may be initially depressed and then elevated above normal, but the nature of the response depends upon the stage in the intraerythrocytic cycle and in some cases upon the concentration of the inhibitor used. 3. After ca 2 hr incubation of cultures with inhibitors ATP levels appear to be stabilized and are similar to those of untreated parasites. However, ADP levels of trophozoites show significant increases after a 2 hr incubation with inhibitors, particularly with oligomycin and to a lesser extent with antimycin A; increases in ADP levels however were not observed in ring-stages of the parasite. 4. Inhibition of red cell and parasite glycolysis leads to rapid decreases in parasite ATP levels which are not significantly affected by oligomycin. Incubation of in vitro cultures with oligomycin can result in a decreased, rather than increased rate of lactate production with a concomitant appearance of pyruvate in the growth medium. 5. This investigation would indicate that if there is a mitochondrial contribution to the parasite ATP pool it is relatively small, and that a short-fall in this contribution is quickly compensated for by ATP from other source(s), although this is not necessarily met by increased glycolysis.
Fry
M
M
Wellcome Research Laboratories, Beckenham, Kent, UK.
Webb
E
E
Pudney
M
M
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone); D009840:Oligomycins / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011190:Potassium Cyanide / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D011808:Quinone Reductases / Q000037:antagonists & inhibitors; D012402:Rotenone / Q000494:pharmacology
D007773:Lactates; D009840:Oligomycins; D011773:Pyruvates; D012402:Rotenone; D019344:Lactic Acid; D004024:Dicyclohexylcarbodiimide; D000244:Adenosine Diphosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D014450:Electron Transport Complex III; D011190:Potassium Cyanide