Figure 1.

Central role of PA phosphatase in the synthesis of triacylglycerol and membrane phospholipids in mammalian cells. The structures of CDP-diacylglycerol, PA, diacylglycerol, and triacylglycerol are shown with the C16:0 and C18:1 fatty acyl groups. PA phosphatase plays a major role in governing whether cells utilize PA for the synthesis of triacylglycerol via diacylglycerol or for the synthesis of membrane phospholipids via CDP-diacylglycerol. The PA phosphatase reaction is counterbalanced by the conversion of diacylglycerol to PA. The major phospholipids phosphatidylcholine and phosphatidylethanolamine are synthesized from the PA-derived diacylglycerol via the CDP-choline and CDP-ethanolamine branches, respectively, of the Kennedy pathway. Phosphatidylcholine is also synthesized from phosphatidylethanolamine by the three-step methylation reactions using AdoMet as a methyl donor. Phosphatidylserine is derived from phosphatidylcholine or phosphatidylethanolamine via a base-exchange reaction, and its decarboxylation produces phosphatidylethanolamine. In addition to their roles in lipid synthesis, PA and diacylglycerol are known to facilitate membrane fission/fusion events (96–101) and play roles in vesicular trafficking (102–106). More comprehensive pathways of lipid synthesis may be found in Ref. 2. DAG, diacylglycerol; TAG, triacylglycerol; PI, phosphatidylinositol; PG, phosphatidylglycerol; CL, cardiolipin; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; Cho, choline; Etn, ethanolamine.