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 phosp hatidylethano-lamine (PE). Steps in the utilization of ethanolamine co uld represent novel targets for the development of chemotherapeutic dr ugs and were therefore investigated in detail. Transport of [H-3]ethan olamine was studied using structural analogs of ethanolamine. Compound s with substitutions in the amino group or of one of the methylene hyd rogens of ethanolamine were the most effective inhibitors, Those analo gs studied in detail with respect to their kinetic properties were all found to be competitive inhibitors of ethanolamine transport. Followi ng uptake, ethanolamine is rapidly phosphorylated by an ethanolamine-s pecific kinase to form phosphoethanolamine. Other acid-soluble interme diates identified by thin layer chromatography were CDP-ethanolamine, dCDP-ethanolamine, and glycero-phosphorylethanolamine. The relative am ounts of these metabolites varied between slender (dividing) and stump y (non-dividing) trypanosomes and may reflect special biosynthetic nee ds of the different morphological forms, Pulse-chase experiments indic ated that the acid-soluble metabolites served as precursors for chloro form/methanol-soluble Lipids. Radioactive lipids included PE, mono-met hyl 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 tryp anosomes are able to synthesize phospholipids via the Kennedy pathway.