Role and Regulation of Glutathione Metabolism in Plasmodium falciparum

Molecules

Sylke Müller¹ 

[1] Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK; E-Mail

关键词: malaria;    glutathione;    drug discovery;    drug target;    redox metabolism;    antioxidant;   

DOI  :  10.3390/molecules200610511

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.