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Synthesis of Phosphatidylcholine in the ER Membrane
Glycerophospholipids, such as phosphatidylcholine, are one of the major components of eukaryotic cell membranes.
It is an important building block for new membranes during cell growth and division.
Additionally, it maintains membrane integrity and participates in cell signaling pathways.
Phosphatidylcholine is mainly synthesized in the ER using three primary reactants — free fatty acids, glycerol phosphate, and cytidine-diphosphocholine or CDP-choline, in the presence of enzymes embedded in the ER membrane.
As they are hydrophobic, free fatty acids use fatty acid-binding proteins to navigate through the cytosol. On reaching the ER membrane, they are activated by acyl-CoA ligase.
The membrane acyltransferase combines two activated fatty acids with glycerol phosphate to form a molecule of phosphatidic acid, which is inserted in the membrane.
Next, the phosphate head group of phosphatidic acid is removed by an enzyme phosphatase, converting phosphatidic acid into diacylglycerol.
Finally, choline phosphotransferase transfers the choline group from CDP-choline to diacylglycerol, resulting in a phosphatidylcholine molecule in the cytosolic leaflet of the ER membrane.
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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.
Suggested Reading
- Furse, Samuel, and Anton IPM De Kroon. "Phosphatidylcholine's functions beyond that of a membrane brick." Molecular membrane biology 32, no. 4 (2015): 117-119.
- van der Veen, Jelske N., John P. Kennelly, Sereana Wan, Jean E. Vance, Dennis E. Vance, and René L. Jacobs. "The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease." Biochimica et Biophysica Acta (BBA)-Biomembranes 1859, no. 9 (2017): 1558-1572.