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.

Open in a new window

Sources and fates of metabolites