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

16 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.
LanguageEnglish
Pages872-882
Number of pages11
JournalGlycobiology
Volume20
Issue number7
Early online date24 Mar 2010
DOIs
Publication statusPublished - Jul 2010

Fingerprint

UTP-Glucose-1-Phosphate Uridylyltransferase
Uridine Diphosphate Galactose
Uridine Diphosphate Glucose
Leishmania major
Salvaging
Uridine Diphosphate
Glycocalyx
Leishmania
Biosynthesis
Parasites
Phosphorylation
Gene encoding
Glycoconjugates
Gene Deletion
Galactose
Sugars
Virulence
Nucleotides
Chemical activation

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

Cite this

Lamerz, Anne-Christin ; Damerow, Sebastian ; Kleczka, Barbara ; Wiese, Martin ; van Zandbergen, Ger ; Lamerz, Jens ; Wenzel, Alexander ; Hsu, Fong-Fu ; Turk, John ; Beverley, Stephen M ; Routier, Françoise H. / Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major. In: Glycobiology. 2010 ; Vol. 20, No. 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.",
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author = "Anne-Christin Lamerz and Sebastian Damerow and Barbara Kleczka and Martin Wiese and {van Zandbergen}, Ger and Jens Lamerz and Alexander Wenzel and Fong-Fu Hsu and John Turk and Beverley, {Stephen M} and Routier, {Fran{\cc}oise H}",
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Lamerz, A-C, Damerow, S, Kleczka, B, Wiese, M, van Zandbergen, G, Lamerz, J, Wenzel, A, Hsu, F-F, Turk, J, Beverley, SM & Routier, FH 2010, 'Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major' Glycobiology, vol. 20, no. 7, pp. 872-882. https://doi.org/10.1093/glycob/cwq045

Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major. / Lamerz, Anne-Christin; Damerow, Sebastian; Kleczka, Barbara; Wiese, Martin; van Zandbergen, Ger; Lamerz, Jens; Wenzel, Alexander; Hsu, Fong-Fu; Turk, John; Beverley, Stephen M; Routier, Françoise H.

In: Glycobiology, Vol. 20, No. 7, 07.2010, p. 872-882.

Research output: Contribution to journalArticle

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T1 - Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major

AU - Lamerz, Anne-Christin

AU - Damerow, Sebastian

AU - Kleczka, Barbara

AU - Wiese, Martin

AU - van Zandbergen, Ger

AU - Lamerz, Jens

AU - Wenzel, Alexander

AU - Hsu, Fong-Fu

AU - Turk, John

AU - Beverley, Stephen M

AU - Routier, Françoise H

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N2 - 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.

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KW - sequence deletion

KW - signal transduction

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