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

Birkholtz, Lyn-Marie; Williams, Marni; Niemand, Jandeli; Louw, Abraham I.; Persson, Lo LU and Heby, Olle (2011) In Biochemical Journal 438. p.229-244
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... (More)
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. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
keywords
alpha-difluoromethylornithine, Leishmania, malaria, ornithine, decarboxylase (ODC), polyamine, S-adenosylmethionine decarboxylase, (AdoMetDC), spermidine synthase, Trypanosoma
in
Biochemical Journal
volume
438
pages
229 - 244
publisher
Portland Press Limited
external identifiers
  • wos:000295195400001
  • scopus:80051673618
ISSN
0264-6021
DOI
10.1042/BJ20110362
language
English
LU publication?
yes
id
5e78eddd-463d-4c4a-b8dc-dad3b7e36a3b (old id 2180025)
date added to LUP
2011-11-01 07:49:02
date last changed
2017-10-22 04:25:02
@article{5e78eddd-463d-4c4a-b8dc-dad3b7e36a3b,
  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.},
  author       = {Birkholtz, Lyn-Marie and Williams, Marni and Niemand, Jandeli and Louw, Abraham I. and Persson, Lo and Heby, Olle},
  issn         = {0264-6021},
  keyword      = {alpha-difluoromethylornithine,Leishmania,malaria,ornithine,decarboxylase (ODC),polyamine,S-adenosylmethionine decarboxylase,(AdoMetDC),spermidine synthase,Trypanosoma},
  language     = {eng},
  pages        = {229--244},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities},
  url          = {http://dx.doi.org/10.1042/BJ20110362},
  volume       = {438},
  year         = {2011},
}