Glycosylphosphatidylinositol (GPI) anchor biosynthesis

Glycosylphosphatidylinositol anchors are glycolipids composed of phosphatidylinositol and the carbohydrate residues, glucosamine and mannose. The carbohydrates are glycosidically attached to the inositol groups. These can be attached to the C-terminal of proteins via post-translational modifications. The fatty acid chains within the phosphatidylinositol residues are hydrophobic and therefore anchor proteins to membranes. The carbohydrate moieties, glucosamine and mannose are provided by the substrates UDP-N-acetyl-glucosamine and dolichyl-phosphate D-mannose from the aminosugars metabolism and N-glycan biosynthesis pathways respectively. The synthesis of GPI anchors start at the outside of the ER membrane and the transfer of phosphoethanolamine group takes place inside of ER membrane. The proteins which are transferred to GPI anchor have a signal peptide (cleavage site, spacer and hydrophobic stretch) near the C-terminus. As they have a stretch of hydrophobic amino acids, they are attached to the ER membrane. GPI anchor transamidase cleaves the appropriate peptide bond and transfers GPI anchor to the protein. These GPI-anchored proteins process through the secretory pathway and ends up in the outer side of plasma membrane.

 

Enzyme EC Number Gene id
Manosyltransferase - PIG M 2.4.1.- Chro.10419
Manosyltransferase - PIG V 2.4.1.- Chro.60588
Dolichyl-phosphate-mannose-glycolipid a-mannosyltransferase 2.4.1.130 Chro.30406
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 Chro.10380
Phosphatidylinositol N-acetylglucosaminyltransferase - PIG-P 2.4.1.198 Chro.20095
Phosphatidylinositol N-acetylglucosaminyltransferase - PIG-A 2.4.1.198 Chro.40236
Phosphatidylinositol N-acetylglucosaminyltransferase - PIG-A 2.4.1.198 Chro.50057
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 Chro.50196
N-acetylglucosaminylphosphatidylinositol deacetylase 3.5.1.89 Missing in annotation
GPI anchor transamidase - PIG-U none Chro.10032
GPI anchor transamidase - PIG-T none Chro.60376
PIG-O none Chro.80266
PIG-W none Missing in annotation

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Phosphatidyl-1D-myo-inositol Inositol phosphate metabolism    
UDP-N-acetyl-glucosamine Aminosugars metabolism Acetate Pyruvate metabolism
Palmitoyl-CoA Fatty acid elongation in the ER    
Dolichyl-P-mannose N-glycan biosynthesis Dolichyl-P N-glycan biosynthesis
Phosphatidylethanolamine Phosphatidylethanolamine and phosphatidylserine metabolism