title: Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities.
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.
authors.affiliation: Department of Biochemistry, University of Pretoria, Hatfield, South Africa. lbirkholtz@up.ac.za
authors.forename: Lyn-Marie
authors.initials: LM
authors.lastname: Birkholtz
authors.forename: Marni
authors.initials: M
authors.lastname: Williams
authors.forename: Jandeli
authors.initials: J
authors.lastname: Niemand
authors.forename: Abraham I
authors.initials: AI
authors.lastname: Louw
authors.forename: Lo
authors.initials: L
authors.lastname: Persson
authors.forename: Olle
authors.initials: O
authors.lastname: Heby
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D010271:Parasites / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D011073:Polyamines / Q000378:metabolism*
chemical_list: D000981:Antiprotozoal Agents; D011073:Polyamines