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.- CMU_019870
Manosyltransferase - PIG V 2.4.1.- CMU_021580
Dolichyl-phosphate-mannose-glycolipid a-mannosyltransferase 2.4.1.130 CMU_016380
Phosphatidylinositol N-acetylglucosaminyltransferase - PIG-P 2.4.1.198 CMU_009540
Phosphatidylinositol N-acetylglucosaminyltransferase - PIG-A 2.4.1.198 CMU_016320
Phosphatidylinositol N-acetylglucosaminyltransferase - PIG-C 2.4.1.198 CMU_020210
Phosphatidylinositol N-acetylglucosaminyltransferase - PIG-H 2.4.1.198 CMU_021030
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 CMU_039980
N-acetylglucosaminylphosphatidylinositol deacetylase 3.5.1.89 CMU_032640
GPI anchor transamidase none CMU_001180
GPI anchor transamidase - PIG-U none CMU_006330
PIG-O none CMU_026240
GPI anchor transamidase - PIG-T none CMU_031310
GPI anchor transamidase - PIG-U none CMU_034890
PIG-W none Missing in annotation

 

Open in a new window

 

 

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