Abstract
The proliferation of the intraerythrocytic malaria parasite is dependent on the uptake from the blood plasma, and from the cytoplasm of the host cell, of a range of essential nutrients. These compounds are taken up into the parasitised cell via a combination of constitutively active endogenous host cell transporters and new parasite-induced permeability pathways. On entering the infected cell they are taken up by the intracellular parasite, across the parasitophorous vacuole and parasite plasma membranes, via a combination of channels and transporters, and/or via endocytosis. Once inside the parasite, nutrients are typically phosphorylated and thereby effectively trapped within the cell. The intraerythrocytic parasite has a range of subcellular membrane-bound organelles, each endowed with their own complement of transport proteins which mediate the uptake and efflux of metabolic substrates and byproducts. Proteins that mediate the uptake, intracellular trafficking and metabolism of essential nutrients in the Plasmodium-infected erythrocyte are potential antimalarial drug targets. Here we consider the nature of the pathways involved, focusing in particular on those that mediate the uptake of three important nutrients: glucose, the key energy-substrate for the parasite; pantothenate (vitamin B5), the precursor of the important enzyme cofactor, coenzyme A; and choline, the precursor of the phospholipid phosphatidylcholine.
Keywords: Malaria, glucose, pantothenate, choline, antimalarial
Current Drug Targets
Title: Targeting Nutrient Uptake Mechanisms in Plasmodium
Volume: 8 Issue: 1
Author(s): Kiaran Kirk and Kevin J. Saliba
Affiliation:
Keywords: Malaria, glucose, pantothenate, choline, antimalarial
Abstract: The proliferation of the intraerythrocytic malaria parasite is dependent on the uptake from the blood plasma, and from the cytoplasm of the host cell, of a range of essential nutrients. These compounds are taken up into the parasitised cell via a combination of constitutively active endogenous host cell transporters and new parasite-induced permeability pathways. On entering the infected cell they are taken up by the intracellular parasite, across the parasitophorous vacuole and parasite plasma membranes, via a combination of channels and transporters, and/or via endocytosis. Once inside the parasite, nutrients are typically phosphorylated and thereby effectively trapped within the cell. The intraerythrocytic parasite has a range of subcellular membrane-bound organelles, each endowed with their own complement of transport proteins which mediate the uptake and efflux of metabolic substrates and byproducts. Proteins that mediate the uptake, intracellular trafficking and metabolism of essential nutrients in the Plasmodium-infected erythrocyte are potential antimalarial drug targets. Here we consider the nature of the pathways involved, focusing in particular on those that mediate the uptake of three important nutrients: glucose, the key energy-substrate for the parasite; pantothenate (vitamin B5), the precursor of the important enzyme cofactor, coenzyme A; and choline, the precursor of the phospholipid phosphatidylcholine.
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Cite this article as:
Kirk Kiaran and Saliba J. Kevin, Targeting Nutrient Uptake Mechanisms in Plasmodium, Current Drug Targets 2007; 8 (1) . https://dx.doi.org/10.2174/138945007779315560
DOI https://dx.doi.org/10.2174/138945007779315560 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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