Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism.
Trypanosomes and leishmania, the causative agents of several tropical diseases, possess a unique redox metabolism which is based on trypanothione. The bis(glutathionyl)spermidine is the central thiol that delivers electrons for the synthesis of DNA precursors, the detoxification of hydroperoxides and other trypanothione-dependent pathways. Many of the reactions are mediated by tryparedoxin, a distant member of the thioredoxin protein family. Trypanothione is kept reduced by the parasite-specific flavoenzyme trypanothione reductase. Since glutathione reductases and thioredoxin reductases are missing, the reaction catalyzed by trypanothione reductase represents the only connection between the NADPH- and the thiol-based redox metabolisms. Thus, cellular thiol redox homeostasis is maintained by the biosynthesis and reduction of trypanothione. Nearly all proteins of the parasite-specific trypanothione metabolism have proved to be essential.
Krauth-Siegel
R Luise
RL
Biochemie-Zentrum der Universität Heidelberg, 69120 Heidelberg, Germany. luise.krauth-siegel@bzh.uni-heidelberg.de
Comini
Marcelo A
MA
D000818:Animals; D018105:DNA, Kinetoplast / Q000096:biosynthesis; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010271:Parasites / Q000378:metabolism*; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014345:Trypanosoma / Q000378:metabolism*
D018105:DNA, Kinetoplast; D013438:Sulfhydryl Compounds; C044809:trypanothione; D005978:Glutathione; D013095:Spermidine