Abstract
This chapter discusses the role of polyamines in malarial parasites. Polyamines are ubiquitous cell components that play roles in the regulation of gene expression, macromolecular syntheses, differentiation, and proliferation. Eukaryotes contain the polyamines putrescine (PU), spermidine (SPD), and mostly spermine (SM). Human red cells, devoid of ornithine decarboxylase (ODC) and S -adenosyl methionine decarboxylase (AdoMetDC) activity, lack the capacity for the synthesis of polyamines and as a result, intracellular levels are low, principally obtained by uptake. The precursor for polyamine synthesis in mammalian cells as well as in Plasmodium falciparum is arginine that is converted by arginase to urea and ornithine; the latter is subsequently decarboxylated by ODC to PU. This chapter discusses the research of Metcalf and colleagues (1978) who developed α-difluoromethylornithine (DFMO), a derivative of the amino acid ornithine that leads to irreversible inhibition of the enzyme ODC by alkylation of its active site and depletes the cell of intracellular polyamines that in turn results in a slowing down of proliferation of many cell types. A discussion is also presented on ODC and AdoMetDC that are usually derived from separate genes, and act individually as highly regulated monofunctional enzymes.
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