Phospholipid Biosynthesis

This pathway describes the synthesis of the common phospholipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and cardiolipins. Phospholipids can be synthesized by two mechanisms. One utilizes a CDP-activated polar head group for attachment to the phosphate of phosphatidic acid. The other utilizes CDP-activated 1,2-diacylglycerol and an inactivated polar head group. Phospholipids are synthesized in the ER membrane from cytosolic precursors. Two fatty acids linked to coenzyme A (CoA) carriers are first joined to glycerol-3-phosphate, yielding phosphatidic acid, which is simultaneously inserted into the membrane. A phosphatase then converts phosphatidic acid to diacylglycerol. The attachment of different polar head groups to diacylglycerol then results in formation of phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine. Phosphatidylinositol is formed from phosphatidic acid, rather than from diacylglycerol. Initially, most phospholipids have a saturated fatty acid on C-1 and an unsaturated fatty acid on C-2 of the glycerol backbone. However, the fatty acid distribution at the C–1 and C–2 positions of glycerol within phospholipids is continually in flux, owing to phospholipid degradation and the continuous phospholipid remodeling that occurs while these molecules are in membranes. In many cases the acyl group which was initially transferred to glycerol, by the action of the acyl transferases, is not the same acyl group present in the phospholipid when it resides within a membrane. The remodeling of acyl groups in phospholipids is the result of the action of phospholipase A1 (PLA1) and phospholipase A2 (PLA2). The most commonly added alcohols (serine, ethanolamine and choline) also contain nitrogen that may be positively charged, whereas, glycerol and inositol do not.

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