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

Anne Christin Lamerz, Sebastian Damerow, Barbara Kleczka, Martin Wiese, Ger Van Zandbergen, Jens Lamerz, Alexandear Wenzel, Fong Fu Hsu, John Turk, Stephen M. Beverley, Françoise H. Routier

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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: α-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 ofthe 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.

Original languageEnglish
Pages (from-to)872-882
Number of pages11
JournalGlycobiology
Volume20
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • Nucleotide sugars metabolism
  • Trypanosomatids
  • UDP-galactose
  • UDP-glucose

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