Metabolism of 1-0-[1'-14C]octadecyl-sn-glycerol in Leishmania donovani promastigotes. Ether lipid synthesis and degradation of the ether bond.

A long-chain 0-alkylglycerol, 1-0-[1'-14C]octadecyl-sn-glycerol, was taken up and metabolized extensively in Leishmania donovani promastigotes grown on a lipid-free, semi-defined medium as well as on a lipid-free, synthetic medium in nearly identical ways. Cleavage of the ether bond was the main event even after short incubation times (1 h) and low precursor concentration (2 microM), as judged from the appearance of radioactive acyl moieties residing mainly in phosphatidylcholine. In addition, labeled plasmanyl inositol and plasmenyl ethanolamine were formed to a considerable extent. However, when administered in higher concentrations (25 microM), 1-0-alkyl-sn-glycerols as well as their enantiomers inhibited lipid metabolism dramatically, accompanied by rounding of the cells and appearance of cellular debris in the medium. This effect was not dependent on the aliphatic side chain (12:0, 16:0, 18:0, 18:1) of the 0-alkylglycerols. It is suggested that, by incorporation into cellular membranes, 0-alklglycerols affect factors responsible for the interaction of membranes and the cytoskeleton as well as enzymes of lipid metabolism.

Ether lipid synthesis from enantiomeric medium-chain and long-chain O-alkyl-sn-glycerols in Leishmania donovani promastigotes.

A medium-chain O-alkylglycerol, 1-O-[1'-14C]dodecyl-sn-glycerol, has been found to be incorporated into plasmenyl ethanolamine by Leishmania donovani promastigotes as revealed by radio gas-liquid chromatography; however, the ether bond of the administered O-alkyl-glycerol was cleaved extensively as judged from the occurrence of radioactive acyl moieties. The labelling pattern produced by the radioactive 'natural' 1-O-octadecyl-sn-glycerol was similar though the latter served as a slightly better substrate for plasmalogens. Experiments with the enantiomeric 3-O-alkyl-sn-glycerols in comparison revealed that these were poor substrates for plasmalogen synthesis, although they were taken up in identical amounts and cleaved even to a higher extent. Therefore, we conclude the 1-0-alkyl-sn-glycerols were utilized directly for plasmenyl ethanolamine synthesis. The incorporation of the dodecyl residue into plasmenyl ethanolamine did not affect the multiplication and shape of cells.