This pathway describes the synthesis of the common phospholipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and cardiolipins. Phospholipid synthesis is mediated by two possible mechanisms: (1) A CDP-activated polar head group for attaches to the phosphate of phosphatidic acid or (2) A CDP-activated 1,2-diacylglycerol and an inactivated polar head group. The ER membrane is the primary site of phospholipid synthesis using precursors imported into the ER from the cytosol. To initiate the process, phosphatidic acid is generated by the linkage of two fatty acids associated with coenzyme A (CoA) carriers to glycerol-3-phosphate. This new molecule is inserted into the membrane where a phosphatase converts it into diacylglycerol or alternatively it is formed into phosphatidylinositol before the conversion. If the conversion into diacylglycerol occurs, the molecule has three possible fates depending on the type of polar head group attached: phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine. At their inception, a phospholipid is composed of a saturated fatty acid and unsaturated fatty acid on the C1 and C2 carbon of the glycerol backbone respectively. With the continuous remodelling of the phospholipid bilayer, this fatty acid distribution at these carbons changes. For example, acyl group remodelling changes the presence of acyl groups on the glycerol backbone (which were initially placed there by acyl transferases) and moves it further into the membrane as a consequence of the action of phospholipase A1 (PLA1) and phospholipase A2 (PLA2). Another modifying group that is usually added are alcohol-containing groups such as serine, ethanol amine, and choline which contain positively-charged nitrogen.

Phospholipid Biosynthesis References