• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Biosynthetic Mechanisms of LTA-type Epoxides and Novel Bioactive Lipid Mediators

    Jin, Jing
    : https://etd.library.vanderbilt.edu/etd-08232013-110456
    http://hdl.handle.net/1803/13986
    : 2013-09-19

    Abstract

    Biosynthesis of lipid mediators including the leukotrienes, lipoxins, eoxins, resolvins, and protectins entails the lipoxygenase (LOX) catalyzed synthesis of an allylic epoxide intermediate, designated as leukotriene A4 (LTA4) and LTA analogues, and heretofore considered too unstable for direct structural characterization. In this dissertation I developed methods involving biphasic reaction conditions for the LOX-catalyzed synthesis of LTA epoxides and their structural analysis by NMR. As proof of concept, human 15-LOX-1 was shown to convert 15S-hydroperoxyeicosatetraenoic acid (15S-HPETE) to the LTA analogue, 14,15-LTA4 (thus identifying eoxin A4). Using this methodology I then showed that recombinant Arabidopsis AtLOX1, an arachidonate 5-LOX, converts 5S-HPETE to the trans epoxide LTA4, and 5R-HPETE to the cis epoxide 5-epi-LTA4. The results are reconciled with a mechanism based on a dual role of the LOX non-heme iron in LTA epoxide biosynthesis. The same methodology was used to structurally characterize the LTA-related epoxides from omega-3 fatty acids, including identification of the proposed epoxide intermediate in protectin biosynthesis.
    Show full item record

    Files in this item

    Icon
    Name:
    Jin.pdf
    Size:
    5.277Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy