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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Biosynthesis of Glycosylphosphatidylinositols in Mammals and Unicellular Microbes

A. Tiede / I. Bastisch / J. Schubert / P. Orlean / R. E. Schmidt

Citation Information: Biological Chemistry. Volume 380, Issue 5, Pages 503–524, ISSN (Print) 1431-6730, DOI: 10.1515/BC.1999.066, June 2005

Publication History

Published Online:
2005-06-01

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 pharmacotherapeuticsthat selectively inhibit GPI biosynthesis in unicellular microbes.

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