EFFECT OF PHOSPHATIDYLCHOLINE ON PHOSPHATIDYLCHOLINE BIOSYNTHESIS IN TETRAHYMENA - DIFFERENTIAL RESPONSES TO INHIBITION BY THE S-ADENOSYLHOMOCYSTEINE ANALOGS 5'-DEOXY-5'-ISOBUTYLTHIOADENOSINE (SIBA) AND 5'-DEOXY-5'-ISOBUTYLTHIO-3-DEAZAADENOSINE (DZ-SIBA)

Exposure of Tetrahymena to high doses of the S-adenosylhomocysteine an alogues SIBA(4) and dz-SIBA leads to strong growth inhibition, abnorma l cell morphology and inhibition of phosphatidylcholine formation both by methylation of phosphatidylethanolamine and by incorporation of ch oline via the cholinephosphotransferase pathway, as determined by meas uring alterations in the relative incorporation of [H-3-CH3]choline an d [C-14-CH3]methionine into the phospholipids of the organism during g rowth. Inclusion of phosphatidylcholine or choline in the growth mediu m with dz-SIBA reverses the morphological distortions but only phospha tidylcholine reverses the growth inhibition as well. By contrast, the growth inhibition produced by SIBA is not reversed by phosphatidylchol ine, indicating that the two inhibitors produce their effects by diffe rent processes. Growth of uninhibited cells with phosphatidylcholine r esults in significant reduction in both choline and methionine incorpo ration into phosphatidylcholine and an increase in cellular phosphatid ylcholine content from approximately 15% to 40% of the total cellular phospholipids pointing to direct uptake of the intact phospholipid.