Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major

Lamerz, Anne-Christin and Damerow, Sebastian and Kleczka, Barbara and Wiese, Martin and van Zandbergen, Ger and Lamerz, Jens and Wenzel, Alexander and Hsu, Fong-Fu and Turk, John and Beverley, Stephen M and Routier, Françoise H (2010) Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major. Glycobiology, 20 (7). pp. 872-882.

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Abstract

The nucleotide sugar UDP-galactose (UDP-Gal) is essential for the biosynthesis of several abundant glycoconjugates forming the surface glycocalyx of the protozoan parasite Leishmania major. Current data suggest that UDP-Gal could arise de novo by epimerization of UDP-glucose (UDP-Glc) or by a salvage pathway involving phosphorylation of Gal and the action of UDP-glucose:alpha-D-galactose-1-phosphate uridylyltransferase as described by Leloir. Since both pathways require UDP-Glc, inactivation of the UDP-glucose pyrophosphorylase (UGP) catalyzing activation of glucose-1 phosphate to UDP-Glc was expected to deprive parasites of UDP-Gal required for Leishmania glycocalyx formation. Targeted deletion of the gene encoding UGP, however, only partially affected the synthesis of the Gal-rich phosphoglycans. Moreover, no alteration in the abundant Gal-containing glycoinositolphospholipids was found in the deletion mutant. Consistent with these findings, the virulence of the UGP-deficient mutant was only modestly affected. These data suggest that Leishmania elaborates a UDP-Glc independent salvage pathway for UDP-Gal biosynthesis.

ORCID iDs

Lamerz, Anne-Christin, Damerow, Sebastian, Kleczka, Barbara, Wiese, Martin ORCID logoORCID: https://orcid.org/0000-0003-4493-0835, van Zandbergen, Ger, Lamerz, Jens, Wenzel, Alexander, Hsu, Fong-Fu, Turk, John, Beverley, Stephen M and Routier, Françoise H;
  • Item type:Article
    ID code:33843
    Dates:
    Date
    Event
    July 2010
    Published
    24 March 2010
    Published Online
    Keywords:amino acid sequence, animals, humans, leishmania major, macrophages, mice, mice, inbred BALB C, molecular sequence data, sequence deletion, signal transduction, UTP-glucose-1-phosphate uridylyltransferase, uridine diphosphate galactose, uridine diphosphate glucose, Pharmacy and materia medica, Biochemistry
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:11 Oct 2011 14:52
    Last modified:20 Jan 2021 19:36
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/33843
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