The lipid bilayers of cell membranes are mainly composed of phospholipids such as phosphatidlylcholine (PC) and phosphatidylethanolamine (PE). Leishmania, obligate protozoan parasites that cause leishmaniasis disease affecting 12 million people worldwide, have phosphatidylcholine as the most abundant membrane phospholipid. However the regulation of the choline or ethanolamine utilization by these organisms is not well established. Thus, choline or ethanolamine transport into the cell and phosphatidylcholine synthesis by the CDP-choline pathway and by the methylation of phosphatidylethanolamine by phosphatidylethanolamine methyltransferase were evaluated using Leishmania tarentolae cells. We also evaluated how a series of choline analogs affected the transport and/or synthesis of phosphatidylcholine by incubating cells with either 14C-choline or 14C-ethanolamine, adding various choline analogs and determining the amount of radiolabeled phospholipid following extraction (method of Bligh and Dyer, 1959) and thin layer chromatography. The most effective inhibitor decreased de novo synthesis of PC by ~77%.These analogs may provide a new therapeutic direction in Leishmania treatment.

Choline analog inhibition of choline or ethanolamine transport and incorporation into phospholipids by <i>Leishmania tarentolae</i>

243rd National Meeting (2012)

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Choline analog inhibition of choline or ethanolamine transport and incorporation into phospholipids by Leishmania tarentolae