Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism

• Published in: Biochimica et biophysica acta Vol. 1780; no. 11; pp. 1236 - 1248
• Main Authors: Krauth-Siegel, R. Luise, Comini, Marcelo A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2008
• Subjects: Animals; DNA, Kinetoplast - biosynthesis; Glutaredoxin; Glutathione - analogs & derivatives; Glutathione - chemistry; Glutathione - metabolism; Glutathione peroxidase; Glutathionylation; Oxidation-Reduction; Parasites - metabolism; Peroxiredoxin; Spermidine - analogs & derivatives; Spermidine - chemistry; Spermidine - metabolism; Sulfhydryl Compounds - metabolism; Thiol metabolism; Thioredoxin; Trypanosoma; Trypanosoma - metabolism; Trypanothione; Tryparedoxin; Peroxiredoxin; Glutathione peroxidase; Trypanosoma; Tryparedoxin; Thiol metabolism; Glutaredoxin; Glutathionylation; Thioredoxin; Trypanothione
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2008.03.006

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.