The fate of phosphatidylcholine on low densitiy lipoproteins (LDL) removed by the liver

Considerable attention has been devoted to studying the capacity of LDL to deliver cholesterol to cells by endocytic and selective uptake. However, less is known about the uptake and metabolism of phospholipids present in these lipoproteins. We have studied the uptake of phosphatidylcholine (PC), the major phospholipid present in LDL particles, by cultures of primary hepatocytes. When PC was labeled with [ 3 H]choline, [ 3 H]PC was incorporated into hepatocytes without significant metabolism to lysoPC or water‐soluble compounds. Apparently, PC avoided the lysosomes and, therefore, was not degraded by the hepatocytes. When PC was labeled with either [ 3 H]oleic acid or [ 3 H]palmitic acid, neither free fatty acids nor lysoPC were produced, confirming a lack of degradation. Surprisingly, half of the labeled fatty acids from PC were incorporated into triacylglycerol (TG). This process was a coenzyme A‐independent reaction since triacsin C, an inhibitor of fatty acyl‐CoA synthetase, was unable to block TG production. Finally, PC uptake was studied utilizing both wild type and LDL receptor knockout hepatocytes. The incorporation of PC into hepatocytes was inhibited up to 35% in the absence of LDL receptor whereas cholesteryl ether uptake was inhibited by over 70%. This finding suggests that there might be additional proteins involved in the transport of PC from LDL particles to hepatocytes. In conclusion, our results suggest that LDL receptor is only partially involved in the uptake of PC. Moreover, LDL‐derived PC in hepatocytes is converted to TG rather than degraded in lysosomes as occurs for LDL‐derived cholesteryl esters. Supported by CIHR.