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 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.

 

This pathway is same in Plasmodium falciparum and the Coccidians Toxoplasma gondii and Neospora caninum, although the number of isoforms of phosphatidylinositol N-acetylglucosaminyltransferase and GPI-anchor transamidase present in the species differs.

 

Enzyme EC Number Gene id
Manosyltransferase - PIG V 2.4.1.- NCLIV_036430
Manosyltransferase - PIG M 2.4.1.- NCLIV_054210
Dolichyl-phosphate-mannose-glycolipid a-mannosyltransferase 2.4.1.130 NCLIV_004260
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 NCLIV_009460
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 NCLIV_017280
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 NCLIV_019400
N-acetylglucosaminylphosphatidylinositol deacetylase 3.5.1.89 NCLIV_028260
GPI-anchor transamidase - PIG-U none NCLIV_007520
GPI-anchor transamidase none NCLIV_010770
PIG-O none NCLIV_047790
GPI-anchor transamidase - PIG-U none NCLIV_050880
PIG-W none NCLIV_051950
GPI-anchor transamidase - PIG-T none NCLIV_060640
GPI-anchor transamidase - PIG-U none NCLIV_068290

 

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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