Glycosylphosphatidylinositol

Glycosylphosphatidylinositol (GPI) is a glycolipid that can be attached to the C-terminus of a protein during posttranslational modification. It is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker (glucosamine and mannose glycosidically bound to inositol) to the C-terminal amino acid of a mature protein.

Structure

The GPI anchor is a complex glycolipid that links proteins to the cell surface. The core structure of the GPI anchor is conserved across all eukaryotes, and consists of ethanolamine phosphate, three mannose residues, a non-N-acetylated glucosamine, and a molecule of phosphatidylinositol. The phosphatidylinositol can be acylated at the inositol ring by a fatty acid chain.

Function

GPI-anchored proteins (GPI-APs) have various functions including enzyme activities, receptor activities, adhesion, and antigenicity. They are found on the surface of various types of cells, including erythrocytes, lymphocytes, and macrophages. GPI-APs are also involved in several diseases, such as paroxysmal nocturnal hemoglobinuria (PNH) and African sleeping sickness.

Biosynthesis

The biosynthesis of GPI is a complex process that occurs in the endoplasmic reticulum (ER). It involves the sequential addition of sugars and other components to phosphatidylinositol. The process is initiated by the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol.

Clinical significance

Defects in GPI biosynthesis are associated with several diseases, including PNH and inherited GPI deficiency. In PNH, the most common clinical manifestation is hemolytic anemia due to the increased sensitivity of erythrocytes to complement-mediated lysis.