Metabolism and functions of trypanothione in the kinetoplastida

Alan H. Fairlamb, Anthony Cerami

    Research output: Contribution to journalReview articlepeer-review

    704 Citations (Scopus)

    Abstract

    Trypanosomatids differ from all other organisms in their ability to conjugate the sulfur-containing tripeptide, glutathione, and the polyamine, spermidine, to form trypanothione [N1,N8-bis(glutathionyl)spermidine]. Together with the NADPH-dependent flavoprotein, trypanothione reductase, the dithiol form of trypanothione provides an intracellular reducing environment in these parasites, substituting for glutathione and glutathione reductase found in the mammalian host. Trypanothione and its related enzymes are involved in defense against damage by oxidants, certain heavy metals, and possibly xenobiotics. Trypanothione and its metabolic precursor, glutathionylspermidine, are also implicated in the modulation of spermidine levels during growth. Several existing trypanocidal drugs interact with the trypanothione system, suggesting that trypanothione metabolism may be a good target for the development of new drugs. The purification and properties of three key enzymes (glutathionylspermidine synthetase, trypanothione synthetase, and trypanothione reductase) are discussed, and the catalytic mechanism, substrate-specificity, and the three-dimensional structure of trypanothione reductase are compared to that of glutathione reductase.

    Original languageEnglish
    Pages (from-to)695-729
    Number of pages35
    JournalAnnual Review of Microbiology
    Volume46
    DOIs
    Publication statusPublished - 1992

    Keywords

    • chemotherapy
    • flavoprotein disulfide oxidoreductases
    • glutathione
    • polyamines
    • protozoan parasites

    ASJC Scopus subject areas

    • Microbiology

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