What is the acid synthesized in the liver, stored in the gallbladder (GB), and secreted from the bile duct?

Bile Acids: Synthesis, Storage, and Secretion

Bile acids are synthesized in the liver from cholesterol, stored in the gallbladder, and secreted through the bile duct into the intestine. 1

Bile Acid Synthesis

Bile acids are the end products of cholesterol metabolism, produced through a complex biosynthetic pathway in the liver:

• Primary synthesis pathway: Occurs in the liver through enzymatic conversion of cholesterol

  • Two primary bile acids are produced: cholic acid (CA) and chenodeoxycholic acid 1, 2
  • Requires at least 17 different enzymes plus transport proteins 3
  • Key enzymes include 3β-D5-hydroxy-C27-steroid oxidoreductase (3β-HSD) and D4-3-oxosteroid-5β-reductase (D4-3-oxoR) 1

• Acidic (alternative) pathway:

  • Involves initial hydroxylation by sterol 27-hydroxylase (CYP27A1)
  • Subsequent 7α-hydroxylation by oxysterol 7α-hydroxylase (CYP7B1) 4
  • Helps control cellular cholesterol and lipid homeostasis

• Post-synthesis modification:

  • Bile acids are conjugated with glycine or taurine in the liver 5, 6
  • Conjugation increases their solubility and makes them impermeable to cell membranes 5

Storage and Concentration

After synthesis, bile acids follow this pathway:

• Secreted from liver into bile
• Transported to the gallbladder via the bile ducts
• Concentrated in the gallbladder during fasting periods 2
• Released into the small intestine in response to dietary fat 2

Secretion and Enterohepatic Circulation

The secretion and recycling of bile acids involves:

• Expulsion from gallbladder into the duodenum through the bile duct when stimulated by cholecystokinin after meals
• Active reabsorption in the terminal ileum (95% of bile acids are reabsorbed) 1
• Return to the liver via portal circulation
• Multiple enterohepatic circulations before eventual excretion 5
• Bacterial transformation in the colon to secondary bile acids 2

Physiological Functions

Bile acids serve multiple critical functions:

• Facilitate absorption of dietary lipids and fat-soluble vitamins in the intestine 5, 2
• Induce biliary lipid secretion 5
• Solubilize cholesterol in bile, promoting its elimination 5
• Act as signaling molecules that regulate:
  • Lipid metabolism
  • Glucose metabolism
  • Energy homeostasis 2
• Activate nuclear receptors (FXR) and membrane receptors (GPBAR-1/TGR5) 2

Clinical Relevance

Disorders of bile acid metabolism can manifest as:

• Cholestatic liver diseases, which may benefit from ursodeoxycholic acid (UDCA) treatment 1, 5
• Bile acid malabsorption, causing diarrhea that responds to bile acid sequestrants 1, 7
• Inborn errors of bile acid synthesis, which are rare genetic disorders requiring specific treatment with primary bile acids 1, 3

Understanding the synthesis, storage and secretion of bile acids is essential for diagnosing and managing various hepatobiliary and intestinal disorders.