Bile acid synthesis and transport

Question 1

Function of bile acids

Answer 1

• Regulates its own synthesis
• Emulsification and absorption of dietary fats/TAGs
• Cholesterol homeostasis
• Absorption of fat soluble vitamins
• Signal transduction

Question 2

Bile acid synthesis

Answer 2

• Made from cholesterol in liver, secreted into bile in conjugated form (glycine or taurine), more hydrophilic
• We make only primary bile acids, bacteria break these down into secondary (more hydrophobic) BAs

Question 3

Regulation of bile acid synthesis

Answer 3

• CYP7A1 is rate limiting step in synthesis
• The nz adds an OH group (primary), which bacteria will remove to make the salt more hydrophobic (secondary)
• Bile acids enter enterocytes via ABST, and bind to nuclear receptors (FXR) that lead to release of factors (FGF-19) into the blood which inhibit production CYP7A1
• Similarly, bile acids from blood can enter hepatocytes via ABST and then affect CYP7A1 production thru nuclear receptors (FXR)
• Majority of ABST proteins found in terminal ileum

Question 4

Enterohepatic circulation and bile acid transport

Answer 4

• Bile acids are re-absorbed primarily in terminal ileum, 10% lost in stool
• Extracted from portal blood into liver and re-conjugated, 10% go into systemic circulation and are filtered out by kidney
• The secondary forms cannot be re-converted into 1o forms, but can be re-conjugated to be more hydrophilic
• When there is cholestasis the bile backs up in the liver, and the liver dumps the bile into systemic circulation (bilirubin goes up, mostly D bili)

Question 5

Bile acid and cholesterol level relationships

Answer 5

• Cholesterol levels can be lowered by binding up bile acids (cholestyramine)
• This leads to increased BA production and thus usage of more cholesterol
• Urodiol can be used to Rx gallstones and PSC/PBC, thought to work by decreasing cholesterol absorption and increasing flow of bile