Functional consequences of perturbing polyamine metabolism in the malaria parasite, Plasmodium falciparum

Inhibition of polyamine biosynthesis and/or the perturbation of polyamine functionality have been exploited with success against parasitic diseases such as Trypanosoma infections. However, when the classical polyamine biosynthesis inhibitor, α-difluoromethylornithine, is used against the human malar...

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Bibliographic Details
Published in:Amino acids 2010-02, Vol.38 (2), p.633-644
Main Authors: Clark, K, Niemand, J, Reeksting, S, Smit, S, van Brummelen, A. C, Williams, M, Louw, A. I, Birkholtz, L
Format: Article
Language:English
Subjects:
Analytical Chemistry
Animals
Biochemical Engineering
Biochemistry
Biomedical and Life Sciences
Biosynthesis
Drugs
Erythrocytes
Humans
Inhibition
Inhibitors
Life Sciences
Malaria
Malaria, Falciparum - parasitology
Metabolism
Neurobiology
Parasites
Plasmodium falciparum
Plasmodium falciparum - enzymology
Plasmodium falciparum - genetics
Plasmodium falciparum - metabolism
Polyamines
Polyamines - metabolism
Proteins
Proteomics
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Review Article
Trypanosoma
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Summary:Inhibition of polyamine biosynthesis and/or the perturbation of polyamine functionality have been exploited with success against parasitic diseases such as Trypanosoma infections. However, when the classical polyamine biosynthesis inhibitor, α-difluoromethylornithine, is used against the human malaria parasite, Plasmodium falciparum, it results in only a cytostatic growth arrest. Polyamine metabolism in this parasite has unique properties not shared by any other organism. These include the bifunctional arrangement of the catalytic decarboxylases and an apparent absence of the typical polyamine interconversion pathways implying different mechanisms for the regulation of polyamine homeostasis that includes the uptake of exogenous polyamines at least in vitro. These properties make polyamine metabolism an enticing drug target in P. falciparum provided that the physiological and functional consequences of polyamine metabolism perturbation are understood. This review highlights our current understanding of the biological consequences of inhibition of the biosynthetic enzymes in the polyamine pathway in P. falciparum as revealed by several global analytical approaches. Ultimately, the evidence suggests that polyamine metabolism in P. falciparum is a validated drug target worth exploiting.
ISSN:0939-4451
1438-2199
DOI:10.1007/s00726-009-0424-7