15.17: Synthesis of Phosphatidylcholine in the ER Membrane
The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
The major components of all eukaryotic cell membranes are glycerophospholipids, sphingolipids, and sterols. Glycerophospholipids play diverse functions in a cell. They act as a barrier for transporting compounds across the membrane, serve as secondary messengers, and store energy. The most abundant glycerophospholipids in higher eukaryotic cell membranes are phosphatidylcholine and phosphatidylethanolamine.
Synthesis of Phosphatidylcholine
Phosphatidylcholine synthesis in nucleated mammalian cells occurs by the CDP-choline pathway or the Kennedy pathway using CTP as an energy substrate for metabolite activation. In this pathway, the glycerophospholipids synthesis occurs via modification of phosphatidic acid — the simplest glycerophospholipid with a phosphate head group. Enzymatic alterations to the phosphate head group yield important membrane glycerophospholipids, such as phosphatidylcholine and phosphatidylethanolamine.
Subcellular roles of Phosphatidylcholine
Besides its role in membrane building, phosphatidylcholine is vital in synthesizing and stabilizing lipoproteins like VLDL, a significant component of the lipid droplets. In the liver cells, the molar ratio of phosphatidylcholine to phosphatidylethanolamine in the plasma membrane affects the integrity of cells, which is critical for normal functioning. The compromised membranes result in the ballooning of the hepatocytes linked to conditions such as non-alcoholic fatty liver disease leading to liver failure. The rate of synthesis and acyl-chain composition of phosphatidylcholine vary as per tissue-specific needs. For example, saturated dipalmitoyl-phosphatidylcholine helps reduce surface tension in the lung alveoli, especially in neonatal infants.
