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

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dc.contributor.author Clark, Katherine
dc.contributor.author Niemand, Jandeli
dc.contributor.author Reeksting, S.B. (Shaun Bernard)
dc.contributor.author Smit, Salome
dc.contributor.author Van Brummelen, A.C. (Anna Catharina)
dc.contributor.author Williams, Marni
dc.contributor.author Louw, Abraham Izak
dc.contributor.author Birkholtz, Lyn-Marie
dc.date.accessioned 2011-08-08T08:51:21Z
dc.date.available 2011-08-08T08:51:21Z
dc.date.issued 2010-02
dc.description.abstract 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. en
dc.description.sponsorship This work was supported by the National Research Foundation of South Africa (NRF: Grant FA2004051300055, FA2006040400011 and FA2007050300003), the University of Pretoria and the Department of Science and Technology of South Africa for funding the South African Malaria Initiative of which LB and AIL are members. KC, TvB, SS and MW were recipients of prestigious bursaries from the NRF, South Africa. JN hold bursaries from the Carl and Emily Fuchs Foundation as well as the Ernst and Ethel Eriksen Trust. en_US
dc.description.uri www.springerlink.com en_US
dc.identifier.citation Clark, K, Niemand, J, Reeksting, SB, Smit, S, Van Brummelen, AC, Williams, M, Louw, AI & Birkholtz, L 2010, 'Functional consequences of perturbing polyamine metabolism in the malaria parasite, Plasmodium falciparum', Amino Acids, vol. 38, no. 2, pp. 633-644. en
dc.identifier.issn 0939-4451 (print)
dc.identifier.issn 1438-2199 (online)
dc.identifier.other 10.1007/s00726-009-0424-7
dc.identifier.uri http://hdl.handle.net/2263/17029
dc.language.iso en en_US
dc.publisher Springer en_US
dc.rights © Springer-Verlag 2009. The original publication is available at www.springerlink.com en_US
dc.subject Difluoromethylornithine en
dc.subject.lcsh Polyamines -- Synthesis en
dc.subject.lcsh Plasmodium falciparum en
dc.subject.lcsh Parasites -- Functional genomics en
dc.subject.lcsh Malaria -- Chemotherapy en
dc.title Functional consequences of perturbing polyamine metabolism in the malaria parasite, Plasmodium falciparum en
dc.type Postprint Article en


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