Lipid-Linked Oligosaccharide Biosynthesis (Saccharomyces cerevisiae)

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1-3mannose(4)glucoseNAc(2)-PP-Dolmannose(8)glucoseNAc(2)-PP-Doldolichol-phosphatemannose(5)glucoseNAc(2)-PP-Dolglucose(2)mannose(9)glucoseNAc(2)-PP-DolGDP-mannosedolichyl phosphate D-mannoseglucoseMannose(9)glucoseNAc(2)-PP-DolGDP-mannosemannose(6)glucoseNAc(2)-PP-Doldolichol-phosphatedolichyl phosphate D-mannoseGDP-mannoseGDP-mannosedolichyl phosphate D-mannosemannoseGlucose NAc(2)-PP-Doldolichol-phosphatemannose(9)glucoseNAc(2)-PP-Dolmannose(2)GlucoseNAc(2)-PP-Doldolichol-phosphateglucose(3)mannose(9)glucoseNAc(2)-PP-DolMannose(3)GlucoseNAc(2)-PP-Dolmannose(7)glucoseNAc(2)-PP-Doldolichyl phosphate D-mannoseGDPALG8GDPALG9DIE2GDPECM39L-arginineALG6ALG2ALG11GDPECM40


Description

In eukaryotes, N-linked (asparagine-linked) glycosylation is the most common form of protein modification of secretory and membrane proteins, and is involved in a variety of cellular processes, such as protein folding, sorting and stability (reviewed in (CITS: [15189166][8472892][3896128])). The initial steps of N-linked glycosylation, which are also known as the dolichol pathway of N-linked glycosylation, and lipid- and dolichol-linked oligosaccharide biosynthesis, involve the synthesis of a core oligosaccharide (glucosyl)3(mannosyl)9(N-acetylglucosamine)2, abbreviated, Glc3Man9GlcNAc2, on the lipid carrier, dolichol-pyrophosphate (Dol-PP) (reviewed in (CITS: [9878760][8472892][3896128])). The ordered assembly of the core oligosaccharide is highly conserved throughout eukaryotic evolution. The assembly starts on the cytoplasmic side of the endoplasmic reticulum (ER), where N-acetylglucosamine-1-phosphate (GlcNAc-1-phosphate) is transferred from uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc) to dolichol-phosphate (Dol-P) followed by the addition of one N-acetylglucosamine (GlcNAc) and five mannose residues from UDP-GlcNAc and guanosine 5'-diphosphomannose (GDP-Man), respectively. The resulting lipid-linked precursor (Man5GlcNAc2-PP-Dol) is translocated "flipped" into the lumen of the ER by a flippase, which which is endoded by RFT1 in S. cerevisiae. Once in the lumen, the oligosaccharide is extended by four mannose and three glucose residues derived from dolichyl-phosphate-mannose (Dol-P-Man) and dolichyl-phosphate-glucose (Dol-P-Glc), respectively. The enzyme complex oligosaccharyltransferase (OST) transfers the preassembled oligosaccharide, Glc3Man9GlcNAc2, from the lipid carrier Dol-PP to selected asparagine residues of nascent polypeptides as the polypeptides pass into the lumen of the ER (CITS: [11580295])(CITS: [9405463]). Once attached to the protein, the N-linked oligosaccharide is further modified by a series of trimming and elongation reactions beginning in the ER and ending in the late Golgi compartment (CITS: [8054711]). In the ER, the oligosaccharide is trimmed of its 3 glucose residues and a specific mannose residue to form Man8GlcNAc2. The glucose residues are removed by glucosidases I and II, and in S. cerevisiae the mannose is removed by the alpha-1,2-mannosidase Mns1p, which is part of the editing mechanism that promotes the exit of correctly folded glycoproteins from the ER (CITS: [9732283]). Once the four monosaccharides are removed, the glycoproteins are transported from the ER to the Golgi, where the yeast and mammalian pathways diverge (CITS: [3304149]). The lipid-linked oligosaccharide biosynthetic pathway is of particular interest in humans, because defects in the glycosyltransferases involved lead to congenital disorders of glycosylation (CITS: [11306275][17024709]). SOURCE: SGD pathways, http://pathway.yeastgenome.org/server.html

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GenMAPP remarks 
Based on http://pathway.yeastgenome.org/biocyc/

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Ontology Terms

 

Bibliography

  1. Cipollo JF, Trimble RB, Chi JH, Yan Q, Dean N; ''The yeast ALG11 gene specifies addition of the terminal alpha 1,2-Man to the Man5GlcNAc2-PP-dolichol N-glycosylation intermediate formed on the cytosolic side of the endoplasmic reticulum.''; J Biol Chem, 2001 PubMed Europe PMC Scholia
  2. Burda P, Aebi M; ''The dolichol pathway of N-linked glycosylation.''; Biochim Biophys Acta, 1999 PubMed Europe PMC Scholia
  3. Burda P, Jakob CA, Beinhauer J, Hegemann JH, Aebi M; ''Ordered assembly of the asymmetrically branched lipid-linked oligosaccharide in the endoplasmic reticulum is ensured by the substrate specificity of the individual glycosyltransferases.''; Glycobiology, 1999 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
88690view15:55, 12 August 2016JmeliusOntology Term : 'lipid metabolic pathway' added !
69880view18:30, 11 July 2013EgonwMarked a few DataNodes with CAS registry numbers as metabolites.
69674view20:41, 8 July 2013MaintBotUpdated to 2013 gpml schema
41919view04:54, 2 March 2011MaintBotRemoved redundant pathway information and comments
36652view22:39, 9 April 2010MaintBotDescription and bibliography added from SGD
21656view11:32, 14 November 2008MaintBot[[Pathway:Saccharomyces cerevisiae:Lipid-linked Oligosaccharide Biosynthesis]] moved to [[Pathway:WP464]]: Moved to stable identifier
12770view08:01, 17 May 2008MaintBotautomated metabolite conversion
8816view14:09, 7 January 2008MaintBotAdded to category $category
8814view14:09, 7 January 2008M.BraymerUploaded new pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ALG11GeneProductS000004993 (SGD)
ALG2GeneProductS000003033 (SGD)
ALG6GeneProductS000005528 (SGD)
ALG8GeneProductS000005593 (SGD)
ALG9GeneProductS000005163 (SGD)
DIE2GeneProductS000003459 (SGD)
ECM39GeneProductS000005313 (SGD)
ECM40GeneProductS000004666 (SGD)
GDPMetabolite146-91-8 (CAS)
L-arginineMetabolite74-79-3 (CAS)

Annotated Interactions

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