The liver has a major role in the metabolism of cholesterol, being the main site of lipoprotein assembly and degradation and the only tissue where the metabolism of cholesterol to bile acids occurs. This provides the major pathway for the removal of cholesterol from the body. The results described in this thesis concern the use of specific enzyme inhibitors (58-035, Azacholesterol, Mevinolin) to determine the intracellular use of different sources of cholesterol in monolayers of rat hepatocytes. In particular, the fates of newly synthesized cholesterol from mevalonic acid and cholesterol derived from HDL2 were investigated. Incubation of hepatocyte monolayers with 58-035 resulted in the inhibition of esterification. In the presence of mevalonic acid as a cholesterol source, 58-035 stimulated bile acid synthesis. Azacholesterol inhibited bile acid synthesis, had no effect on cholesterol synthesis, and in the presence of mevalonic acid, stimulated secretion of cholesterol by the hepatocytes; it had no effect on cholesterol esterification. Mevinolin inhibited cholesterol synthesis and as a result inhibited esterification. HDL2, in the presence of mevinolin, was used as a cholesterol source. It stimulated bile acid synthesis and cholesterol esterification. Addition of 58-035 to the system resulted in the inhibition of both esterification and bile acid synthesis. Overall, the results indicated that different intracllular pools of free cholesterol exist and that the inter-relationships of these pools give a complex pattern of flux of intracellular cholesterol between various pathways in the rat hepatocyte.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:383074 |
| Date | January 1988 |
| Creators | Sampson, William James |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/26913 |
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