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 a protein via post-translational modification. 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 dolichol metabolism 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 V 2.4.1.- TA03530
Manosyltransferase - PIG M 2.4.1.- TA08865
Dolichyl-phosphate-mannose-glycolipid a-mannosyltransferase 2.4.1.130 Missing in annotation
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 TA10130
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 TA11115
N-acetylglucosaminylphosphatidyl inositol deacetylase 3.5.1.89 TA10880
GPI-anchor transamidase - PIG-U none TA04035
GPI-anchor transamidase none TA04335
PIG-W none TA05415
GPI-anchor transamidase none TA17465
PIG-O none TA19235

 

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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 Phosphatidylethanolamine metabolism    
Dolichyl-P-mannose Dolichol metabolism Dolichyl-P Dolichol metabolism
Phosphatidylethanolamine Phosphatidylethanolamine metabolism