title: Thiol-based redox metabolism of protozoan parasites.
abstract: The review considers redox enzymes of Plasmodium spp., Trypanosomatida, Trichomonas, Entamoeba and Giardia, with special emphasis on their potential use as targets for drug development. Thiol-based redox systems play pivotal roles in the success and survival of these parasitic protozoa. The synthesis of cysteine, the key molecule of any thiol metabolism, has been elucidated in trypanosomatids and anaerobes. In trypanosomatids, trypanothione replaces the more common glutathione system. The enzymes of trypanothione synthesis have recently been identified. The role of trypanothione in the detoxification of reactive oxygen species is reflected in the multiplicity of trypanothione-dependent peroxidases. In Plasmodium falciparum, the crystal structures of glutathione reductase and glutamate dehydrogenase are now available; another drug target, thioredoxin reductase, has been demonstrated to be essential for the malarial parasite.
authors.affiliation: Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, DD1 5EH, Dundee, UK.
authors.forename: Sylke
authors.initials: S
authors.lastname: Müller
authors.forename: Eva
authors.initials: E
authors.lastname: Liebau
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Walter
authors.forename: R Luise
authors.initials: RL
authors.lastname: Krauth-Siegel
mesh_terms: D000818:Animals; D015195:Drug Design; D056890:Eukaryota / Q000201:enzymology / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D013095:Spermidine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D013879:Thioredoxins; C044809:trypanothione; D005969:Glutamate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005978:Glutathione; D013095:Spermidine