Document Detail


Biosynthesis of glycosylphosphatidylinositols of Plasmodium falciparum in a cell-free incubation system: inositol acylation is needed for mannosylation of glycosylphosphatidylinositols.
MedLine Citation:
PMID:  10585859     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The structures of glycosylphosphatidylinositols (GPIs) in Plasmodium have been described [Gerold, Schuppert and Schwarz (1994) J. Biol. Chem. 269, 2597-2606]. A detailed understanding of GPI synthesis in Plasmodium is a prerequisite for identifying differences present in biosynthetic pathways of parasites and host cells. A comparison of the biosynthetic pathway of GPIs has revealed differences between mammalian cells and parasitic protozoans. A cell-free incubation system prepared from asexual erythrocytic stages of Plasmodium falciparum, the causative agent of malaria in humans, is capable of synthesizing the same spectrum of GPIs as that found in metabolically labelled parasites. The formation of mannosylated GPIs in the cell-free system is shown to be inhibited by GTP and, unexpectedly, micromolar concentrations of GDP-Man. Lower concentrations of GDP-Man affect the spectrum of GPIs synthesized. The inositol ring of GPIs of P. falciparum is modified by an acyl group. The preferred donor of this fatty acid at the inositol ring is myristoyl-CoA. Inositol acylation has to precede the mannosylation of GPIs because, in the absence of acyl-CoA or CoA, mannosylated GPIs were not detected. Inositol myristoylation is a unique feature of plasmodial GPIs and thus might provide a potential target for drug therapy.
Authors:
P Gerold; N Jung; N Azzouz; N Freiberg; S Kobe; R T Schwarz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  344 Pt 3     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-03-17     Completed Date:  2000-03-17     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  731-8     Citation Subset:  IM    
Affiliation:
Medizinisches Zentrum für Hygiene und Medizinisches Mikrobiologie, Philipps-Universität, Robert-Koch Strasse 17, D-35037 Marburg, Germany. gerold@mailer.uni-marburg.de
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MeSH Terms
Descriptor/Qualifier:
Acetylglucosamine / metabolism
Acyl Coenzyme A / metabolism
Acylation
Animals
Cell-Free System
Chromatography, High Pressure Liquid
Chromatography, Thin Layer
Coenzyme A / pharmacology
Glycolipids / analysis,  biosynthesis
Glycosylphosphatidylinositols / biosynthesis*,  metabolism
Guanosine Diphosphate Mannose / metabolism
Inositol / metabolism*
Mannosides / biosynthesis*
Membrane Lipids / analysis,  biosynthesis
Phosphatidylinositols / analysis
Plasmodium falciparum / metabolism*
Chemical
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Glycolipids; 0/Glycosylphosphatidylinositols; 0/Mannosides; 0/Membrane Lipids; 0/Phosphatidylinositols; 3123-67-9/Guanosine Diphosphate Mannose; 3130-72-1/S-tetradecanoyl-coenzyme A; 6917-35-7/Inositol; 7512-17-6/Acetylglucosamine; 85-61-0/Coenzyme A
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