Ovothiol and trypanothione as antioxidants in trypanosomatids

Mark R. Ariyanayagam, Alan H. Fairlamb (Lead / Corresponding author)

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    174 Citations (Scopus)

    Abstract

    The relative amounts of ovothiol A (N1-methyl-4-mercaptohistidine) and trypanothione [N1,N8-bis(glutathionyl)spermidine] have been determined in all life cycle stages of representative trypanosomatids (Leishmania spp, Crithidia fasciculata, Trypanosoma cruzi and T. brucei). Ovothiol A is present in all insect stages with intracellular concentrations of > 1 mM for five species of Leishmania promastigotes and < 0.25 mM for other trypanosomatids. In Leishmania promastigotes, ovothiol A can exceed trypanothione content particularly in late logarithmic and stationary phases of growth. In the other trypanosomatids, it represents less than 10% of the total thiol pool. Although amastigotes of L. major and L. donovani contain equivalent amounts of glutathione and trypanothione, ovothiol A is present in the former but absent in the latter. Ovothiol A is present in all developmental stages of T. cruzi but absent in bloodstream trypomastigotes of T. brucei. No ovothiol reductase activity could be detected in dialysed parasite extracts. Ovothiol disulphide is not a substrate for trypanothione reductase, although it can be reduced by the concerted action of trypanothione and trypanothione reductase. No ovothiol-dependent peroxidase activity was present in Leishmania extracts. Although ovothiol A can act as a non-enzymatic scavenger of hydrogen peroxide, it is less efficient than trypanothione. Second order rate constants were determined with trypanothione > glutathionylspermidine > ovothiol > glutathione. Given the presence of an active trypanothione peroxidase system in all these trypanosomatids, it is concluded that under physiological conditions, ovothiol is unlikely to play a major role in the metabolism of hydrogen peroxide in intact cells. Nonetheless, since ovothiol is absent in host macrophage, kidney and CHO cells, this metabolite may have other important functional roles in trypanosomatids that could be exploited as a chemotherapeutic target.

    Original languageEnglish
    Pages (from-to)189-198
    Number of pages10
    JournalMolecular and Biochemical Parasitology
    Volume115
    Issue number2
    DOIs
    Publication statusPublished - Jul 2001

    Keywords

    • Glutathione
    • Ovothiol
    • Oxidant stress
    • Peroxidase
    • Trypanosomatid
    • Trypanothione

    ASJC Scopus subject areas

    • Parasitology
    • Molecular Biology

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