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Ethanolamine is found in trypanosomes as an integral component
of the variant surface glycoprotein (VSG) and the membrane phospholipid
phosphatidylethanolamine (PE). Steps in the utilization of ethanolamine
could represent novel targets for the development of chemotherapeutic
drugs and were therefore investigated in detail. Transport of
[
Volume 270,
Number 27,
Issue of July 07, pp. 16160-16166, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
H]ethanolamine was studied using structural
analogs of ethanolamine. Compounds with substitutions in the amino
group or of one of the methylene hydrogens of ethanolamine were the
most effective inhibitors. Those analogs studied in detail with respect
to their kinetic properties were all found to be competitive inhibitors
of ethanolamine transport. Following uptake, ethanolamine is rapidly
phosphorylated by an ethanolamine-specific kinase to form
phosphoethanolamine. Other acid-soluble intermediates identified by
thin layer chromatography were CDP-ethanolamine, dCDP-ethanolamine, and
glycerophosphorylethanolamine. The relative amounts of these
metabolites varied between slender (dividing) and stumpy (non-dividing)
trypanosomes and may reflect special biosynthetic needs of the
different morphological forms. Pulse-chase experiments indicated that
the acid-soluble metabolites served as precursors for
chloroform/methanol-soluble lipids. Radioactive lipids included PE,
mono-methyl and dimethyl PE, and lysoPE. Further methylation of
dimethylPE to phosphatidylcholine was not observed under the
experimental conditions described. These results are consistent with
the conclusion that trypanosomes are able to synthesize phospholipids
via the Kennedy pathway.
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