Relationship between liver injury and production of bile salt and cholesterol elimination in the bile.
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- Introduction to Cholesterol Metabolism
- Biosynthesis of Cholesterol
- Regulation of Cholesterol Synthesis
- Proteolytic Regulation of HMG-CoA Reductase
- Utilization of Cholesterol
- Regulation of Cellular Sterol Content
- Bile Acid Synthesis
- Clinical Significance of Bile Acids
- 1. their synthesis and subsequent excretion in the feces represent the only significant mechanism for the elimination of excess cholesterol.
- 2. bile acids and phospholipids solubilize cholesterol in the bile, thereby preventing the precipitation of cholesterol in the gallbladder.
- 3. they facilitate the digestion of dietary triacylglycerols by acting as emulsifying agents that render fats accessible to pancreatic lipases.
- 4. they facilitate the intestinal absorption of fat-soluble vitamins.
Intestinal Cholesterol Absorption and Its Regulation
Although it is generally thought that the liver makes only a small contribution to whole body sterol synthesis, it has a remarkable capacity to upregulate its rate of cholesterol synthesis when the content of cholesterol in the hepatocyte falls below normal levels. This happens when there is either an acceleration in the rate of conversion of cholesterol to bile acids, or a reduction in the amount of lipoprotein or chylomicron cholesterol entering the liver from the plasma.[7] Hence, although cholesterol absorption inhibitors can be used very effectively as a monotherapy for hypercholesterolemia, their efficacy can potentially be significantly enhanced by coadministration of a statin. With this strategy, the adaptive increase in hepatic cholesterol synthesis is largely blocked, thereby inducing the liver to clear additional amounts of LDL-C from the circulation.
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