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, Alexander Wenzel, Fong-Fu Hsu, John Turk, Stephen M Beverley, Françoise H Routier

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)872-882
Number of pages11
JournalGlycobiology
Volume20
Issue number7
Early online date24 Mar 2010
DOIs
Publication statusPublished - Jul 2010

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

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