2. BILE ACIDS
Synthesized from Cholesterol
There are mainly 4 main bile acids
Structure- They contain 24 carbon atom.
Differ only in the number and position of additional
hydroxyl groups.
4. (1) Classification of bile acids
The primary bile acids are synthesized in the liver
from cholesterol.
• Cholic acid
• Chenodeoxycholic acid
5. The secondary bile acids are products that the
primary bile acids in the intestine are subjected
to some further changes (deconjugation and 7-
α-dehydroxylation) by the activity of the
intestinal bacteria.
• De-Oxycholic acid
• Lithocholic acid
6. Classification of bile acids
Classification
Free bile
acids
Conjugated bile acids
Primary bile
acids
Cholic acid
Glycocholic
acid
Taurocholic acid
Chenodeoxy-
cholic acid
Glycocheno-
deoxycholic
acid
Taurocheno-
deoxycholic acid
Secondary
bile acids
Deoxycholic
acid
Glycodeoxy-
cholic acid
Taurodeoxy-
cholic acid
Lithocholic
acid
Glycolitho-
cholic acid
Taurolitho-cholic
acid
7. (2) Structure of bile acids
HO OH
OH
H
COOH
HO OH
OH
H
CONHCH2COOH
HO OH
H
COOH
HO OH
OH
H
CONHCH2CH2SO3H
cholic acid chenodeoxycholic acid
glycocholic acid taurocholic acid
3 7
12
9. BIOSYNTHESIS OF BILE ACIDS
• Conversion of Cholesterol to 7-α-hydroxycholesterol
– 7-α-hydroxylase, a microsomal enzyme
– Rate limiting reaction
10. • Pathway of bile acid biosynthesis bifurcates
from 7-α-hydroxycholesterol to two directions
– Cholic acid Formation
– Chenodeoxy cholic acid formation
• Conversion of 7-α-hydroxycholesterol to
formation of cholic acid/ chenodeoxycholic acid
– Catalyzed by 12-α-hydroxylase
– Propionyl-CoA is split off the side chain leaving
‘Cholyl CoA’/ “Chenodeoxycholyl-CoA”
• Activated bile acids undergo conjugation with
glycine and taurine to form tauro, glycocholate
and tauro, glycochinodeoxycholate.
11.
12. FATE OF BILE SALT IN THE INTESTINE
• In the intestine, a part of bile acids undergoes
deconjugation and dehydroxylation by
intestinal bacteria
• The product are deoxycholic acid and
lithocholic acid
• Known as Secondary bile acids
13. The reaction/ steps for synthesis of bile
acids are summerzed below:-
1) Cholesterol hydroxylated at 3/7/12 position.
2) Removal of 3 carbon unit, to make it 24C.
3) Conjugation with glycine and taurine.
4) Secretion into intestinal canal.
5) In the intestine, deconjuagtion and removal of
hydroxyl group.
14. (3) Enterohepatic Cycle of bile acids
Conversion to bile salts, that are secreted into the
intestine, is the only mechanism by which
cholesterol is excreted.
Most bile acids are reabsorbed in the ileum ,
returned to the liver by the portal vein, and re-
secreted into the intestine. This is the enterohepatic
cycle.
15.
16. REGULATION OF BILE ACID SYNTHESIS
Constant pool of bile acids is maintained
Principle “rate-limiting” step in the
biosynthesis of bile acid is the 7-α-hydroxylase
step
Cholesterol of endogenous and dietary origin
17.
18. (4) Function of bile acids
Bile acids are amphipathic, with detergent properties.
• Lowering of surface tension
• Bile salt accelerate the action of pancreatic lipase
• Micelles formation
• Absorption of vitamins
• Intestinal motility
• Choleretic action
• Increased solubility of cholesterol
19. CLINICALASPECTS
• Estimation of bile acids and bile salts
in blood
– Bile salts in blood are increased greatly in
clinical obstructive jaundice
• Cholelithiasis (Gall stones)
– Solubility of cholesterol depends on ratio
of cholesterol with conjugated bile salts +
PL
20. • Conditions which favours stone formation
– Infection
• Deconjugation
• phospholipase
– Decreased availability of bile salts
• Defect in enterohepatic circulation
• Disease of terminal ileum
• In patient with cirrhosis liver
• Types of gall stone
– Cholesterol stone- mulberry shaped
– Pigment stones- dark green or black, small multiple stone
– Mixed stones- faceted and dark brown
