Polar Head Group Decarboxylation and Methylation of Phospholipids: An Alternate Route for Phosphatidylcholine Formation in Cultured Neuronal Cells

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Abstract
Decarboxylation of phosphatidylserine (SPG) and methionine-dependent, stepwise methylation of phosphatidylethanolamine (EPG) to form phosphatidylcholine (CPG) were examined in monolayer cultures of rat cerebral cells. Ethanolamine, monomethylaminoethanol or dimethylaminoethanol nitrogenous bases (N-bases) added to culture medium at millimolar level result each in synthesis of the corresponding phospholipid via a de novo pathway at initial rates of 0.18, 0.30 and 0.36 nmol/h/.mu.g DNA, respectively. Addition of methyl-labeled methionine to culture medium at tracer levels or at millimolar concentration enabled measurements of the rates of phospholipid methylation from EPG phosphatidylmonomethylaminoethanol (Me1EPG) and phosphatidyldimethylaminoethanol (Me2EPG) precursors. At tracer doses, the rates of methylation from the above respective phospholipids are 0.45, 1.17 and 1.70 pmol/h/.mu.g DNA. At 1 mM methionine, synthesis of CPG proceeds from [14C]EPG or [14C]Me2EPG at initial rates of 8 and 17 pmol/h/.mu.g DNA, respectively. Although the latter phospholipid analog can be generated from its monomethyl precursor, methylation of EPG does not result in the accumulation of Me2EPG, suggesting 2 segregated and metabolically distinct pathways. In the presence of N-bases, of the total [3H]serine incorporated into cellular phospholipids 30-36.5% of labeled SPG is converted into decarboxylation products. The decarboxylation and methylation routes contribute a significant portion of choline from endogenous sources, most likely through conversion of SPG.