FARNESOL INHIBITS PHOSPHATIDYLCHOLINE BIOSYNTHESIS IN CULTURED-CELLS BY DECREASING CHOLINEPHOSPHOTRANSFERASE ACTIVITY

The mechanism of inhibition of phosphatidylcholine (PC) biosynthesis b y the isoprenoid farnesol was investigated in the human leukaemic CEM- C1 cell line. Cells were preincubated with 20 muM farnesol for up to 2 h and pulsed with [H-3]choline. PC biosynthesis was inhibited to one- quarter at the step catalysed by cholinephosphotransferase (CPT). CPT activity in cellular homogenates from farnesol-treated cells was signi ficantly decreased, but no changes in cytidylyltransferase activity or diacylglycerol concentration were observed. Measurements of CPT activ ity in the experiments in which farnesol was added directly to the hom ogenates or microsomal fractions demonstrated that farnesol did not af fect CPT activity. However, cytosol from farnesol-treated samples decr eased microsomal CPT activity almost twice as much as did cytosol from controls. This effect was found to be heat-stable, and disappeared af ter dialysis, but could not be attributed to farnesol present in the c ytosol. The effect of farnesol was specific when compared with other s tructurally similar isoprenoids. We conclude that farnesol brings abou t changes in cultured cells, leading to decreased CPT activity, and th us to the inhibition of PC biosynthesis.