Week 4: Bile acid synthesis and transport

Question 1

Main functions of bile acids

Answer 1

-Regulates its own synthesis
-emulsification and absorption of dietary fats and TGs
-cholesterol homeostasis
-absorption of fat soluble vitamins
-signal transduction pathways
and more

Question 2

What are the main bile acids?

Answer 2

Primary
-cholic acid
-chenodeoxycholic acid
Secondary: from bacteria removing OH groups, makes them more hydrophobic
-deoxycholic acid
-lithocholic acid

Question 3

Synthesis of bile acids

Answer 3

• Made from cholesterol in the liver
• the first step and rate limiting step is by CYP7A1
• branch point controls how much of each bile acid to make
• following synthesis is a conjugation with glycine or taurine, making glycochenodeoxycholic acid and tauromuricholic acid
• there are two isomers: UDCA and CDCA

Question 4

Regulation of bile acid synthesis

Answer 4

1. bile acids absorbed in terminal ileum. Activates Fxr (nuclear receptor). Produces FGF19 which goes to liver to the receptor FGFR4, leading to inhibition of CYP7A1.
2. Bile acids from intestines transported to hepatocyte. Intake of bile acid in hepatocyte also activates FXR, and produces SHP, which leads to inhibition of CYP7A1.

Question 5

Using regulation of bile acids therapeutically

Answer 5

• lower cholesterol levels by binding bile acid (cholestyramine)
• inhibiting intestinal absorption
• inhibiting cholesterol synthesis with statins

Question 6

Enterohepatic circulation: trace bile acid path

Answer 6

• secreted by the liver (stored by gallbladder or into intestine via bile)
• absorbed by ileum (10% eliminated in stool): via ASBT, shuttled by ILBP, and basolateral export to portal vein via OST
• Enters portal circulation
• extracted by liver via NTCP (conjugated) and OATP (unconjugated) and re-excreted
• transport into bile requires ATP via BSEP
• recirculation occurs 4-6 times with each meal
• 10% gets into systemic circulation and is filtered by kidney