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Plasmodium falciparum: cyanide-resistant oxygen consumption
A D Murphy1, J E Doeller, B Hearn
1Department of Medicine, University of Alabama at Birmingham 35294, USA.
Experimental Parasitology
|October 27, 1997
Summary
Plasmodium falciparum, the malaria parasite, has a unique branched respiratory pathway. This pathway includes a cyanide-resistant component, suggesting a potential new target for antimalarial drugs.
Area of Science:
- Biochemistry
- Parasitology
- Molecular Biology
Background:
- Plasmodium parasites, causative agents of malaria, are hypothesized to possess a branched respiratory pathway.
- This pathway is thought to include both cyanide-sensitive and cyanide-resistant components.
Purpose of the Study:
- To investigate the effect of cyanide on Plasmodium falciparum respiration.
- To provide direct evidence for a branched respiratory pathway in P. falciparum.
- To explore alternative oxidase activity as a potential antimalarial drug target.
Main Methods:
- A polarographic assay was used to measure oxygen consumption in saponin-freed P. falciparum parasites.
- The effects of cyanide, propyl gallate, and salicyclhydroxamic acid on parasite respiration were evaluated.
- In vitro growth inhibition assays were conducted using inhibitors of alternative oxidase activities.
Main Results:
- P. falciparum respiration rate was significantly lower than control cells, suggesting an anabolic role.
- 25% of P. falciparum oxygen consumption was resistant to high concentrations of cyanide.
- Cyanide-resistant respiration was fully inhibited by propyl gallate and salicyclhydroxamic acid.
- These inhibitors also demonstrated efficacy in inhibiting P. falciparum growth in vitro.
Conclusions:
- Direct evidence supports a branched chain respiratory pathway in Plasmodium falciparum.
- Alternative oxidase activity represents a promising chemotherapeutic target for malaria treatment.
- Further research into alternative oxidase inhibitors is warranted for antimalarial drug development.