Biosynthesis of glycosylphosphatidylinositols in mammals and unicellular microbes

Membrane anchoring of cell surface proteins via glycosylphosphatidylinosito l (GPI) occurs in all eukaryotic organisms. In addition, GPI-related glycop hospholipids are important constituents of the glycan coat of certain proto zoa, Defects in GPI biosynthesis can retard, if not abolish growth of these organisms. In humans, a defect in GPI biosynthesis can cause paroxysmal no cturnal hemoglobinuria (PNH), a severe acquired bone marrow disorder. Here, we review advances in the characterization of GPI biosynthesis in parasiti c protozoa, yeast and mammalian cells. The GPI core structure as well as th e major steps in its biosynthesis are conserved throughout evolution. Howev er, there are significant biosynthetic differences between mammals and micr obes. First indications are that these differences could be exploited as ta rgets in the design of novel pharmacotherapeutics that selectively inhibit GPI biosynthesis in unicellular microbes.