Sphingolipid synthesis as a target for chemotherapy against malaria parasites
| Autor: | Nafisa Ghori, Sabine A. Lauer, Kasturi Haldar |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Erythrocytes
Morpholines Plasmodium falciparum Golgi Apparatus Transferases (Other Substituted Phosphate Groups) Sphingomyelin synthase activity Antimalarials symbols.namesake Sphingomyelin synthase Food vacuole Animals Humans Enzyme Inhibitors Malaria Falciparum Sphingolipids Multidisciplinary biology Erythrocyte Membrane Golgi apparatus biology.organism_classification Sphingolipid Cell biology Kinetics Biochemistry Cytoplasm Host cell cytoplasm symbols biology.protein Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 92:9181-9185 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The human malaria parasite Plasmodium falciparum contains sphingomyelin synthase in its Golgi apparatus and in a network of tubovesicular membranes in the cytoplasm of the infected erythrocyte. Palmitoyl and decanoyl analogues of 1-phenyl-2-acylamino-3-morpholino-1-propanol inhibit the enzyme activity in infected erythrocytes. An average of 35% of the activity is extremely sensitive to these drugs and undergoes a rapid, linear decrease at drug concentrations of 0.05-1 microM. The remaining 65% suffers a slower linear inhibition at drug concentrations ranging from 25 to 500 microM. Evidence is presented that inhibition of the sensitive fraction alone selectively disrupts the appearance of the interconnected tubular network in the host cell cytoplasm, without blocking secretory development at the parasite plasma membrane or in organelles within the parasite, such as the Golgi and the digestive food vacuole. This inhibition also blocks parasite proliferation in culture, indicating that the sensitive sphingomyelin synthase activity as well as the tubovesicular network may provide rational targets for drugs against malaria. |
| Databáze: | OpenAIRE |
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