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Molecules 2015, 20(6), 10511-10534; doi:10.3390/molecules200610511

Role and Regulation of Glutathione Metabolism in Plasmodium falciparum

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK
Academic Editor: Angela Calderon
Received: 10 April 2015 / Revised: 11 May 2015 / Accepted: 1 June 2015 / Published: 8 June 2015
(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)
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Abstract

Malaria in humans is caused by one of five species of obligate intracellular protozoan parasites of the genus Plasmodium. P. falciparum causes the most severe disease and is responsible for 600,000 deaths annually, primarily in Sub-Saharan Africa. It has long been suggested that during their development, malaria parasites are exposed to environmental and metabolic stresses. One strategy to drug discovery was to increase these stresses by interfering with the parasites’ antioxidant and redox systems, which may be a valuable approach to disease intervention. Plasmodium possesses two redox systems—the thioredoxin and the glutathione system—with overlapping but also distinct functions. Glutathione is the most abundant low molecular weight redox active thiol in the parasites existing primarily in its reduced form representing an excellent thiol redox buffer. This allows for an efficient maintenance of the intracellular reducing environment of the parasite cytoplasm and its organelles. This review will highlight the mechanisms that are responsible for sustaining an adequate concentration of glutathione and maintaining its redox state in Plasmodium. It will provide a summary of the functions of the tripeptide and will discuss the potential of glutathione metabolism for drug discovery against human malaria parasites. View Full-Text
Keywords: malaria; glutathione; drug discovery; drug target; redox metabolism; antioxidant malaria; glutathione; drug discovery; drug target; redox metabolism; antioxidant
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Müller, S. Role and Regulation of Glutathione Metabolism in Plasmodium falciparum. Molecules 2015, 20, 10511-10534.

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