clinical significance of bile salts

Clinical Significance of Bile Acid Synthesis

Bile acids perform four primary physiologically significant functions:

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.

Over the past several years new insights into the biological activities of the bile acids have been elucidated. Following the isolation and characterization of the farnesoid X receptors (FXRs, see above), for which the bile acids are physiological ligands, the functions of bile acids in the regulation of lipid and glucose homeostasis has begun to emerge. As indicated above, the binding of bile acids to FXRs results in the attenuated expression of several genes involved in overall bile acid homeostasis. However, genes involved in bile acid metabolism are not the only ones that are regulated by FXR action as a consequence of binding bile acid. In the liver, FXR action is known to regulate the expression of genes involved in lipoprotein metabolism (e.g. apoC-II), glucose metabolism (e.g. PEPCK), and hepatoprotection (e.g. CYP3A4, which was originally identified as nifedipine oxidase; nifedipine being a member of the calcium channel blocker drugs). Thus, it is becoming clear that bile acids serve functions not only as intestinal lipid emulsifiers but as significant participants in numerous biochemical and physiological processes.
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