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Biochemical Aspects
of Bile Acids and Salts
Clinical Biochemistry Unit, Path. Dept.
College of Medicine, King Saud University
Objectives
 Structure of primary bile acids and salts
 Structure of secondary bile acids and salts
 Functions of bile salts
 Enterohepatic circulation
 Malabsorption syndrome
 Cholelithiasis
Cholesterol
Cholesterol (27 C) is the:
Parent steroid compound
Precursor of bile acids and salts
Primary Bile Acids
Primary bile acids (24 C):
Amphipathic
-COOH at side chain
Cholic acid: 3 OH
Chenodeoxycholic: 2 OH
Hepatic Synthesis of Bile Acids
The rate-limiting step is
catalyzed by:
Cholesterol 7-α-hydroxylase
Regulation:
Down-regulated by end products
(bile acids) “Enzyme repression”
Up-regulated by cholesterol
“Enzyme induction”
Primary Bile Acids and Salts
Chenodeoxycholic acid
Bile salts (Conjugated bile acids):
amide-linked with glycine or taurine
The ratio of glycine to taurine forms in the bile is
3:1
Glycocholic
Taurocholic
Glycochenodeoxycholic
Taurochenodeoxycholic
Cholic acid BILE ACIDS
BILE SALTS
Bile Salts
 Addition of glycine or taurine results in the
presence of fully ionized groups at pH 7.0:
-COOH of glycine &
-SO3 of taurine
(hence, its name as bile salts e.g.,
Sodium or potassium glycocholate)
 More effective detergent than bile acids
 Only bile salts, but not acids, found in bile
Bile Salts
3
Na or K Glycocholate
Na or K Taurochenodeoxycholate
Hormonal Control
of Bile Secretion
Hormone from gut cells:
Cholecystokinin (CCK)
Responses:
1. Secretion of pancreatic enzymes
2. Bile secretion
3. Slow release of gastric contents
Stimulus:
Undigested lipids and partially digested
proteins in duodenum
Functions of Bile Salts
 Important for cholesterol excretion:
1. As metabolic products of cholesterol
2. Solubilizer of cholesterol in bile
 Emulsifying factors for dietary lipids,
a prerequisite step for efficient lipid digestion
 Cofactor for pancreatic lipase and PLA2
 Facilitate intestinal lipid absorption by
formation of mixed micelle
Emulsification of Dietary Lipids
in Duodenum: Role of Bile Salts
• Emulsification increases the surface area of
lipid droplets, therefore the digestive enzymes
can effectively act.
• Mechanisms:
1. Mechanical mixing by peristalsis
2. Detergent effect of bile salts:
Bile salts interact with lipid particles and aqueous
duodenal contents, stabilizing the particles as they
become smaller, and preventing them from
coalescing.
Absorption of Lipids by Intestinal
Mucosal Cells: Role of Bile salts
Mixed micelles:
Disc-shaped clusters of amphipathic lipids.
Arranged with their hydrophobic groups on the
inside and their hydrophilic groups on the outside.
Micelle includes end products of lipid digestion,
bile salts and fat-soluble vitamins
Note: Short- and medium-chain fatty acids do not
require mixed micelle for absorption by intestinal
cells
The Role of Bile Salts
in Absorption of Lipids
by Intestinal Cells
Mixed Micelle Formation:
Bile salts
End products of lipid digestion
Fat-soluble vitamins
Secondary Bile Acids
Bile salts Glyco- or Tauro-cholate -Chenodeoxycholate
Bile acids Cholic acid Chenodeoxycholic
2° Bile acids Deoxycholic acid Lithocholic
Intestinal bacteria
Intestinal bacteria
Glycine
Taurine
OH
Enterohepatic Circulation
Enterohepatic Circulation
Cholestyramine: Bile acid sequestrants
It binds to bile acids in the gut,
preventing their reabsorption &
Promoting their excretion
It is used for treatment of hypercholesterolemia
Dietary fiber:
It binds to bile acids, increasing their excretion
CONT’D
Maldigestion/Malabsorption
of Lipids
Decreased bile secretion by:
Liver diseases:
e.g., Hepatitis or cirrhosis
Gall bladder diseases:
e.g., Gall stones
Malabsorption of lipids
Cholelithiasis
Cholesterol Gallstone Disease
Causes:
Bile salts in bile:
Biliary tract obstruction
(intereferes with enterohepatic circulation)
Hepatic dysfunction ( synthesis)
Biliary cholesterol excretion
Treatment:
 Bile acid replacement therapy
 Surgical

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Bile acids and salts.pptx

  • 1. Biochemical Aspects of Bile Acids and Salts Clinical Biochemistry Unit, Path. Dept. College of Medicine, King Saud University
  • 2. Objectives  Structure of primary bile acids and salts  Structure of secondary bile acids and salts  Functions of bile salts  Enterohepatic circulation  Malabsorption syndrome  Cholelithiasis
  • 3. Cholesterol Cholesterol (27 C) is the: Parent steroid compound Precursor of bile acids and salts
  • 4. Primary Bile Acids Primary bile acids (24 C): Amphipathic -COOH at side chain Cholic acid: 3 OH Chenodeoxycholic: 2 OH
  • 5. Hepatic Synthesis of Bile Acids The rate-limiting step is catalyzed by: Cholesterol 7-α-hydroxylase Regulation: Down-regulated by end products (bile acids) “Enzyme repression” Up-regulated by cholesterol “Enzyme induction”
  • 6. Primary Bile Acids and Salts Chenodeoxycholic acid Bile salts (Conjugated bile acids): amide-linked with glycine or taurine The ratio of glycine to taurine forms in the bile is 3:1 Glycocholic Taurocholic Glycochenodeoxycholic Taurochenodeoxycholic Cholic acid BILE ACIDS BILE SALTS
  • 7. Bile Salts  Addition of glycine or taurine results in the presence of fully ionized groups at pH 7.0: -COOH of glycine & -SO3 of taurine (hence, its name as bile salts e.g., Sodium or potassium glycocholate)  More effective detergent than bile acids  Only bile salts, but not acids, found in bile
  • 8. Bile Salts 3 Na or K Glycocholate Na or K Taurochenodeoxycholate
  • 9. Hormonal Control of Bile Secretion Hormone from gut cells: Cholecystokinin (CCK) Responses: 1. Secretion of pancreatic enzymes 2. Bile secretion 3. Slow release of gastric contents Stimulus: Undigested lipids and partially digested proteins in duodenum
  • 10. Functions of Bile Salts  Important for cholesterol excretion: 1. As metabolic products of cholesterol 2. Solubilizer of cholesterol in bile  Emulsifying factors for dietary lipids, a prerequisite step for efficient lipid digestion  Cofactor for pancreatic lipase and PLA2  Facilitate intestinal lipid absorption by formation of mixed micelle
  • 11. Emulsification of Dietary Lipids in Duodenum: Role of Bile Salts • Emulsification increases the surface area of lipid droplets, therefore the digestive enzymes can effectively act. • Mechanisms: 1. Mechanical mixing by peristalsis 2. Detergent effect of bile salts: Bile salts interact with lipid particles and aqueous duodenal contents, stabilizing the particles as they become smaller, and preventing them from coalescing.
  • 12. Absorption of Lipids by Intestinal Mucosal Cells: Role of Bile salts Mixed micelles: Disc-shaped clusters of amphipathic lipids. Arranged with their hydrophobic groups on the inside and their hydrophilic groups on the outside. Micelle includes end products of lipid digestion, bile salts and fat-soluble vitamins Note: Short- and medium-chain fatty acids do not require mixed micelle for absorption by intestinal cells
  • 13. The Role of Bile Salts in Absorption of Lipids by Intestinal Cells Mixed Micelle Formation: Bile salts End products of lipid digestion Fat-soluble vitamins
  • 14. Secondary Bile Acids Bile salts Glyco- or Tauro-cholate -Chenodeoxycholate Bile acids Cholic acid Chenodeoxycholic 2° Bile acids Deoxycholic acid Lithocholic Intestinal bacteria Intestinal bacteria Glycine Taurine OH
  • 16. Enterohepatic Circulation Cholestyramine: Bile acid sequestrants It binds to bile acids in the gut, preventing their reabsorption & Promoting their excretion It is used for treatment of hypercholesterolemia Dietary fiber: It binds to bile acids, increasing their excretion CONT’D
  • 17. Maldigestion/Malabsorption of Lipids Decreased bile secretion by: Liver diseases: e.g., Hepatitis or cirrhosis Gall bladder diseases: e.g., Gall stones Malabsorption of lipids
  • 18. Cholelithiasis Cholesterol Gallstone Disease Causes: Bile salts in bile: Biliary tract obstruction (intereferes with enterohepatic circulation) Hepatic dysfunction ( synthesis) Biliary cholesterol excretion Treatment:  Bile acid replacement therapy  Surgical