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J Biol Chem, Vol. 275, Issue 19, 14147-14154, May 12, 2000
From the Department of Biological Chemistry, Johns Hopkins Medical
School, Baltimore, Maryland 21205
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
Mn2+ 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
Glycosyl Phosphatidylinositol Myristoylation in African
Trypanosomes
NEW INTERMEDIATES IN THE PATHWAY FOR FATTY ACID REMODELING*
, and
')
as an intermediate involved in remodeling at the sn-1
position. Second, we found an alternative pathway for production of
glycolipid , 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.
*
This research was supported by National Institutes of Health
Grant AI21334.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Department of Medicine, University of
Pennsylvania School of Medicine, Philadelphia, PA 19104.
§
To whom correspondence should be addressed: Dept. of Biological
Chemistry, Johns Hopkins Medical School, 725 N. Wolfe St., Baltimore,
MD 21205. Tel.: 410-955-3790; Fax: 410-955-7810; E-mail: penglund@jhmi.edu.
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