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 Toxoplasma gondii, although the number of isoforms of phosphatidylinositol N-acetylglucosaminyltransferase and GPI-anchor transamidase present in the species differs.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
Manosyltransferase – PIG V 2.4.1.- TGME49_270220 Plasma membrane Previous publication
Manosyltransferase – PIG M 2.4.1.- TGME49_310100    

Dolichyl-phosphate-mannose-glycolipid a-mannosyltransferase

2.4.1.130 TGME49_321660 Endoplasmic reticulum membrane; Plasma membrane GO annotation; Previous publication
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 TGME49_207980    
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 TGME49_241860    
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 TGME49_280790    
Phosphatidylinositol N-acetylglucosaminyltransferase 2.4.1.198 TGME49_299040    
N-acetylglucosaminylphosphatidyl inositol deacetylase 3.5.1.89 TGME49_258110    
PIG-W none TGME49_214920    
PIG-O none TGME49_224920    
GPI-anchor transamidase none TGME49_319300 Plasma membrane Previous publication
GPI-anchor transamidase - PIG-T none TGME49_308000 Endoplasmic reticulum; Membrane Previous publication; GO annotation
GPI-anchor transamidase - PIG-U none TGME49_252440 Plasma membrane Previous publication
GPI-anchor transamidase - PIG-U none TGME49_275568 Endoplasmic reticulum membrane GO annotation; Previous publication

 

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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