Biosynthesis of glycosylphosphatidylinositols in mammals and unicellular microbes

Andreas Tiede, Ingo Bastisch, Jörg Schubert, Peter Orlean, Reinhold E. Schmidt

Research output: Contribution to journalReview articlepeer-review

Abstract

Membrane anchoring of cell surface proteins via glycosylphosphatidylinositol (GPI) occurs in all eukaryotic organisms. In addition, GPI-related glycophospholipids are important constituents of the glycan coat of certain protozoa. Defects in GPI biosynthesis can retard, if not abolish growth of these organisms. In humans, a defect in GPI biosynthesis can cause paroxysmal nocturnal hemoglobinuria (PNH), a severe acquired bone marrow disorder. Here, we review advances in the characterization of GPI biosynthesis in parasitic protozoa, yeast and mammalian cells. The GPI core structure as well as the major steps in its biosynthesis are conserved throughout evolution. However, there are significant biosynthetic differences between mammals and microbes. First indications are that these differences could be exploited as targets in the design of novel pharmacotherapeutics that selectively inhibit GPI biosynthesis in unicellular microbes.

Original languageEnglish (US)
Pages (from-to)503-523
Number of pages21
JournalBiological Chemistry
Volume380
Issue number5
DOIs
StatePublished - May 1999

Keywords

  • Drug design
  • GPI anchor
  • Glycoprotein
  • Glycosylphosphatidylinositol
  • Paroxysmal nocturnal hemoglobinuria
  • Posttranslational modification

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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