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

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 salvag...

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Bibliographic Details
Published in:Glycobiology (Oxford) 2010-07, Vol.20 (7), p.872-882
Main Authors: 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
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Humans
Leishmania major
Leishmania major - enzymology
Leishmania major - metabolism
Macrophages - metabolism
Mice
Mice, Inbred BALB C
Molecular Sequence Data
nucleotide sugars metabolism
Original
Sequence Deletion
Signal Transduction
trypanosomatids
UDP-galactose
UDP-glucose
Uridine Diphosphate Galactose - chemistry
Uridine Diphosphate Galactose - metabolism
Uridine Diphosphate Glucose - chemistry
Uridine Diphosphate Glucose - metabolism
UTP-Glucose-1-Phosphate Uridylyltransferase - genetics
UTP-Glucose-1-Phosphate Uridylyltransferase - metabolism
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Summary: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 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.
ISSN:0959-6658
1460-2423
DOI:10.1093/glycob/cwq045