| Bile acids are key elements in fat metabolism
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Bile acids have a detergent-like effect, solubilizing biliary lipids and emulsifying dietary fat in the gut to facilitate its digestion (Chapters 9 and 16). They are synthesized by hepatocytes, which hydroxylate cholesterol at the carbon-7 position to produce the primary bile acids, cholic acid and chenodeoxycholic acid. These are conjugated with glucuronic acid, or with the amino acids taurine or glycine, and secreted in bile. In the intestine, the primary bile acids are dehydroxylated by bacteria to form the secondary bile acids: cholic acid is converted to deoxycholic acid, and chenodeoxycholic acid to lithocholic acid. Both primary and secondary bile acids are also deconjugated by bacteria.
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| Intestinal bile acids are reabsorbed and returned to the liver for re-secretion - a process known as the enterohepatic circulation. Elevated plasma, bilirubin levels (levels which occur in liver disease) cause itching.
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| The liver is the major site of both synthesis and catabolism of cholesterol
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| Figure 28.4 Degradation of heme to bilirubin. |
| Indeed, the chenodeoxycholic acid/lithocholic acid pathway is the major route by which cholesterol is excreted. Consequently, the rate of production of bile acids from cholesterol can affect the plasma concentration of low-density lipoprotein (LDL) cholesterol. Increasing the rate of bile acid production lowers the intracellular concentration of cholesterol, upregulates hepatic cell membrane LDL receptors, and enhances the clearance of LDL from plasma. Interrupting the enterohepatic circulation of bile acids by the use of a
nonabsorbable drug that binds them in the gut has the effect of decreasing plasma LDL, and was of therapeutic benefit in hypercholesterolemia (see Chapters 16 and 17).
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