Specificity of ethanolamine transport and its further metabolism in Trypanosoma brucei.
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 [3H]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.
Rifkin
M R
MR
Laboratory of Medical Biochemistry, Rockefeller University, New York, New York 10021, USA.
Strobos
C A
CA
Fairlamb
A H
AH
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003565:Cytidine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D019856:Ethanolamine; D004983:Ethanolamines / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000378:metabolism*
D002352:Carrier Proteins; D004983:Ethanolamines; D008055:Lipids; D010714:Phosphatidylethanolamines; C002449:glycerophosphoethanolamine; C006933:CDP ethanolamine; D019856:Ethanolamine; D003565:Cytidine Diphosphate; C005448:phosphorylethanolamine; D017853:Phosphotransferases (Alcohol Group Acceptor); C020125:ethanolamine kinase