Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities

Lyn-Marie Birkholtz, Marni Williams, Jandeli Niemand, Abraham I. Louw, Lo Persson, Olle Heby

    Research output: Contribution to journalReview articlepeer-review

    64 Citations (SciVal)

    Abstract

    New drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness. Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking polyamine and thiol metabolism in trypanosomatids. Particularly interesting features within polyamine metabolism in these parasites are highlighted for their potential in selective therapeutic strategies.
    Original languageEnglish
    Pages (from-to)229-244
    JournalBiochemical Journal
    Volume438
    DOIs
    Publication statusPublished - 2011

    Subject classification (UKÄ)

    • Biochemistry and Molecular Biology

    Keywords

    • alpha-difluoromethylornithine
    • Leishmania
    • malaria
    • ornithine
    • decarboxylase (ODC)
    • polyamine
    • S-adenosylmethionine decarboxylase
    • (AdoMetDC)
    • spermidine synthase
    • Trypanosoma

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