Acid base homeostasis

1. Bile Acids : Synthesis and Role in
Digestion of Lipids

2. Bile Salts
 Bile acids & salts are effective detergents
 Synthesized in the liver.
 Stored & concentrated in the gallbladder
 Discharged into gut and aides in absorption of intraluminal lipids, cholesterol, & fat
soluble vitamins
 Bile acid refers to the protonated form while bile salts refers to the ionized form
 The pH of the intestine is 7 and the pKa of bile salts is 6, which means that 50% are protonated

3. Synthesis of Bile Salts
 Rate-limiting step performed by the 7α-hydroxylase and is regulated by
bile salt concentration
 End product: Cholic acid & Chenocholic acid
Fig. 9 Fig. 10

5.  The primary bile acids enter the bile as glycine or taurine
conjugates.
 Conjugation takes place in peroxisomes.
 In humans, the ratio of the glycine to the taurine conjugates is
normally 3:1.
 In the alkaline bile, the bile acids and their conjugates are assumed
to be in a salt form—hence the term “bile salts.”
 A portion of the primary bile acids in the intestine is subjected to
further changes by the activity of the intestinal bacteria.

7.  Products of fat digestion, including cholesterol absorbed in the first 100 cm of
small intestine, the primary and secondary bile acids are absorbed almost
exclusively in the ileum, and 98–99% is returned to the liver via the portal
circulation.
 However, lithocholic acid, because of its insolubility, is not reabsorbed to any
significant extent.
 Only a small fraction of the bile salts escapes absorption and is therefore eliminated
in the feces.
Most Bile Acids Return to the Liver
in the Entero-hepatic Circulation

9. Fate of Bile Salts
Fig. 12

10.  The activity of the enzyme is feedback-regulated via the nuclear bile acid-binding
receptor Farnesoid X receptor (FXR)
 When the size of the bile acid pool in the enterohepatic circulation increases, FXR
is activated and transcription of the cholesterol 7-hydroxylase gene is suppressed.
 Chenodeoxycholic acid is particularly important .
 Also enhanced by cholesterol of endogenous and dietary origin and regulated by
insulin, glucagon, glucocorticoids, and thyroid hormone.
Bile Acid Synthesis Is Regulated at the 7-α Hydroxylase
Step

11.  The movement of cholesterol from the liver into
the bile must be accompanied by the
simultaneous secretion of phospholipid and bile
salts.
 If this dual process is disrupted and more
cholesterol enters the bile than can be solubilized
by the bile salts and lecithin present, the
cholesterol may precipitate in the gallbladder,
initiating the occurrence of cholesterol gallstone
disease—cholelithiasis
Bile salt deficiency: Cholelithiasis