Phosphatidylethanolamine in Trypanosoma brucei is organized in two separate pools and is synthesized exclusively by the Kennedy pathway

Aita Signorell, Monika Rauch, Jennifer Jelk, Michael A. J. Ferguson, Peter Buetikofer

    Research output: Contribution to journalArticle

    38 Citations (Scopus)

    Abstract

    Phosphatidylethanolamine is a major phospholipid class of all eukaryotic cells. It can be synthesized via the CDP-ethanolamine branch of the Kennedy pathway, by decarboxylation of phosphatidylserine, or by base exchange with phosphatidylserine. The contributions of these pathways to total phosphatidylethanolamine synthesis have remained unclear. Although Trypanosoma brucei, the causative agent of human and animal trypanosomiasis, has served as a model organism to elucidate the entire reaction sequence for glycosylphosphatidylinositol biosynthesis, the pathways for the synthesis of the major phospholipid classes have received little attention. Wenowshow that disruption of the CDP- ethanolamine branch of the Kennedy pathway using RNA interference results in dramatic changes in phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. By targeting individual enzymes of the pathway, we demonstrate that de novo phosphatidylethanolamine synthesis in T. brucei procyclic forms is strictly dependent on the CDPethanolamine route. Interestingly, the last step in the Kennedy pathway can be mediated by two separate activities leading to two distinct pools of phosphatidylethanolamine, consisting of predominantly alk- 1- enyl- acyl- or diacyl- type molecular species. In addition, we show that phosphatidylserine in T. brucei procyclic forms is synthesized exclusively by base exchange with phosphatidylethanolamine.

    Original languageEnglish
    Pages (from-to)23636-23644
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume283
    Issue number35
    DOIs
    Publication statusPublished - 29 Aug 2008

    Keywords

    • YEAST SACCHAROMYCES-CEREVISIAE
    • PROCYCLIC CULTURE FORMS
    • PHOSPHOLIPID BIOSYNTHESIS
    • MAMMALIAN-CELLS
    • BLOOD-STREAM
    • FATTY-ACID
    • PHOSPHATIDYLSERINE
    • SPECIFICITY
    • METABOLISM
    • LIPIDS

    Cite this

    @article{ae91d9a1bc5b40b4a298e50e881b0ba6,
    title = "Phosphatidylethanolamine in Trypanosoma brucei is organized in two separate pools and is synthesized exclusively by the Kennedy pathway",
    abstract = "Phosphatidylethanolamine is a major phospholipid class of all eukaryotic cells. It can be synthesized via the CDP-ethanolamine branch of the Kennedy pathway, by decarboxylation of phosphatidylserine, or by base exchange with phosphatidylserine. The contributions of these pathways to total phosphatidylethanolamine synthesis have remained unclear. Although Trypanosoma brucei, the causative agent of human and animal trypanosomiasis, has served as a model organism to elucidate the entire reaction sequence for glycosylphosphatidylinositol biosynthesis, the pathways for the synthesis of the major phospholipid classes have received little attention. Wenowshow that disruption of the CDP- ethanolamine branch of the Kennedy pathway using RNA interference results in dramatic changes in phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. By targeting individual enzymes of the pathway, we demonstrate that de novo phosphatidylethanolamine synthesis in T. brucei procyclic forms is strictly dependent on the CDPethanolamine route. Interestingly, the last step in the Kennedy pathway can be mediated by two separate activities leading to two distinct pools of phosphatidylethanolamine, consisting of predominantly alk- 1- enyl- acyl- or diacyl- type molecular species. In addition, we show that phosphatidylserine in T. brucei procyclic forms is synthesized exclusively by base exchange with phosphatidylethanolamine.",
    keywords = "YEAST SACCHAROMYCES-CEREVISIAE, PROCYCLIC CULTURE FORMS, PHOSPHOLIPID BIOSYNTHESIS, MAMMALIAN-CELLS, BLOOD-STREAM, FATTY-ACID, PHOSPHATIDYLSERINE, SPECIFICITY, METABOLISM, LIPIDS",
    author = "Aita Signorell and Monika Rauch and Jennifer Jelk and Ferguson, {Michael A. J.} and Peter Buetikofer",
    year = "2008",
    month = "8",
    day = "29",
    doi = "10.1074/jbc.M803600200",
    language = "English",
    volume = "283",
    pages = "23636--23644",
    journal = "Journal of Biological Chemistry",
    issn = "0021-9258",
    publisher = "American Society for Biochemistry and Molecular Biology",
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    Phosphatidylethanolamine in Trypanosoma brucei is organized in two separate pools and is synthesized exclusively by the Kennedy pathway. / Signorell, Aita; Rauch, Monika; Jelk, Jennifer; Ferguson, Michael A. J.; Buetikofer, Peter.

    In: Journal of Biological Chemistry, Vol. 283, No. 35, 29.08.2008, p. 23636-23644.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Phosphatidylethanolamine in Trypanosoma brucei is organized in two separate pools and is synthesized exclusively by the Kennedy pathway

    AU - Signorell, Aita

    AU - Rauch, Monika

    AU - Jelk, Jennifer

    AU - Ferguson, Michael A. J.

    AU - Buetikofer, Peter

    PY - 2008/8/29

    Y1 - 2008/8/29

    N2 - Phosphatidylethanolamine is a major phospholipid class of all eukaryotic cells. It can be synthesized via the CDP-ethanolamine branch of the Kennedy pathway, by decarboxylation of phosphatidylserine, or by base exchange with phosphatidylserine. The contributions of these pathways to total phosphatidylethanolamine synthesis have remained unclear. Although Trypanosoma brucei, the causative agent of human and animal trypanosomiasis, has served as a model organism to elucidate the entire reaction sequence for glycosylphosphatidylinositol biosynthesis, the pathways for the synthesis of the major phospholipid classes have received little attention. Wenowshow that disruption of the CDP- ethanolamine branch of the Kennedy pathway using RNA interference results in dramatic changes in phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. By targeting individual enzymes of the pathway, we demonstrate that de novo phosphatidylethanolamine synthesis in T. brucei procyclic forms is strictly dependent on the CDPethanolamine route. Interestingly, the last step in the Kennedy pathway can be mediated by two separate activities leading to two distinct pools of phosphatidylethanolamine, consisting of predominantly alk- 1- enyl- acyl- or diacyl- type molecular species. In addition, we show that phosphatidylserine in T. brucei procyclic forms is synthesized exclusively by base exchange with phosphatidylethanolamine.

    AB - Phosphatidylethanolamine is a major phospholipid class of all eukaryotic cells. It can be synthesized via the CDP-ethanolamine branch of the Kennedy pathway, by decarboxylation of phosphatidylserine, or by base exchange with phosphatidylserine. The contributions of these pathways to total phosphatidylethanolamine synthesis have remained unclear. Although Trypanosoma brucei, the causative agent of human and animal trypanosomiasis, has served as a model organism to elucidate the entire reaction sequence for glycosylphosphatidylinositol biosynthesis, the pathways for the synthesis of the major phospholipid classes have received little attention. Wenowshow that disruption of the CDP- ethanolamine branch of the Kennedy pathway using RNA interference results in dramatic changes in phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. By targeting individual enzymes of the pathway, we demonstrate that de novo phosphatidylethanolamine synthesis in T. brucei procyclic forms is strictly dependent on the CDPethanolamine route. Interestingly, the last step in the Kennedy pathway can be mediated by two separate activities leading to two distinct pools of phosphatidylethanolamine, consisting of predominantly alk- 1- enyl- acyl- or diacyl- type molecular species. In addition, we show that phosphatidylserine in T. brucei procyclic forms is synthesized exclusively by base exchange with phosphatidylethanolamine.

    KW - YEAST SACCHAROMYCES-CEREVISIAE

    KW - PROCYCLIC CULTURE FORMS

    KW - PHOSPHOLIPID BIOSYNTHESIS

    KW - MAMMALIAN-CELLS

    KW - BLOOD-STREAM

    KW - FATTY-ACID

    KW - PHOSPHATIDYLSERINE

    KW - SPECIFICITY

    KW - METABOLISM

    KW - LIPIDS

    U2 - 10.1074/jbc.M803600200

    DO - 10.1074/jbc.M803600200

    M3 - Article

    C2 - 18587155

    VL - 283

    SP - 23636

    EP - 23644

    JO - Journal of Biological Chemistry

    JF - Journal of Biological Chemistry

    SN - 0021-9258

    IS - 35

    ER -