Document Detail


Glycosyl phosphatidylinositol myristoylation in African trypanosomes. New intermediates in the pathway for fatty acid remodeling.
MedLine Citation:
PMID:  10799491     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glycosyl phosphatidylinositol (GPI) anchors in the bloodstream form of Trypanosoma brucei are unusual in that their two fatty acids are myristate. The myristates are added in the final stages of GPI biosynthesis in a remodeling reaction. Remodeling occurs first at the sn-2 position of glycerol, involving removal of a longer fatty acid and subsequent attachment of myristate. The second myristate is then incorporated into the sn-1 position, but the mechanism has been unclear due to the unavailability of a reliable cell-free system supporting complete remodeling. Here, we first refined the cell-free system (by removing Mn(2+) ions), thereby allowing efficient production of the dimyristoylated GPI precursor. Using this improved system, we made three new discoveries concerning the pathway for fatty acid remodeling. First, we discovered a monomyristoylated GPI (known as glycolipid theta') as an intermediate involved in remodeling at the sn-1 position. Second, we found an alternative pathway for production of glycolipid theta, the first lyso intermediate in remodeling. The alternative pathway involves an inositol-acylated GPI known as glycolipid lyso-C'. Finally, we found that there is significant breakdown of GPIs during remodeling in the cell-free system, and we speculate that this breakdown has a regulatory role in GPI biosynthesis.
Authors:
Y S Morita; A Acosta-Serrano; L U Buxbaum; P T Englund
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-06-08     Completed Date:  2000-06-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  14147-54     Citation Subset:  IM    
Affiliation:
Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, Maryland 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Fatty Acids / metabolism*
Glycosylphosphatidylinositols / biosynthesis,  metabolism*
Kinetics
Myristic Acid / metabolism*
Trypanosoma brucei brucei / metabolism*
Grant Support
ID/Acronym/Agency:
AI21334/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Glycosylphosphatidylinositols; 544-63-8/Myristic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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