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Bile Salt Synthesis

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					                     Lecture objectives
At the end of the lecture student should be able to understand


  The organic composition of bile.
  The flow of bile.
  The bile acids structure
  The synthesis of the bile acids from cholesterol
  How the bile acid synthesis is regulated by its own feed back inhibition
  The bile salts synthesis
  The functions of bile salts
               Bile and its components
 Bile is a watery mixture of organic and
   inorganic compounds


 Phosphatidylcholine (lecithin)and
   conjugated bile acids (bile salts) are the most
   important organic compounds.




              Flow of bile
 It is synthesized in the liver

 Flows in the duodenum through the bile duct

 Stored in the gall bladder when not needed for
  digestion.
                        Bile acids structure
      The bile acids are amphipathic in nature that is hydroxyl groups are
        at α orientation and methyl groups are at β orientation
      Therefore these molecules have polar and nonpolar face
      They acts as emulsifying agents in the intestine



                 Bile acids from cholesterol
   Formed from cholesterol in the liver
   Stored in the gall bladder in bile as bile salts (sodium and
    potassium)
   Utilized during digestion of fats and other lipid substances (act as
    detergents)
   Rate limiting step is the conversion of cholesterol to 7-alpha
    cholesterol by 7--hydroxylase




                      Synthesis of bile acids
      Bile acids synthesized in liver by a multi-step, multi-organelle pathway
           Hydroxyl groups are inserted at specific positions on the steroid
              structure
           The double bond of the cholesterol B ring is reduced

            The hydrocarbon chain is shortened by three carbons,
             introducing a carboxyl group at the end of the chain

            Resulting into the most common compounds cholic and
             chenodeoxycholic acid(primary bile acids)
                                       NADPH + H+ NADP


HO                                     7a-hydroxylase         HO                      OH


     cholesterol                                                    7a-hydroxycholesterol
                                           12a-hydroxylase
                                            O2; NADPH + H+                           O2
                                            2 CoA-SH                                 NADPH + H+
                                                                                     2 CoA-SH
                            OH

                                           C    S       CoA

                                           O

                                                                                            C     S   CoA

                                                                                            O
 HO                              OH
                    H

                   cholyl-CoA
                                                        HO                      OH
                                                                   H
                                                                   chenodeoxycholyl- CoA

     Bile acids synthesis                                                                   regulation
                                       Types of bile acids
                                      Synthesis of bile salts


                         Approximate composition of bile salts
    Glycocholate – 24%
    Glycochenodeoxycholate – 24%
    Taurocholate – 12%
    Taurochenodeoxycholate – 12%
    Glycodeoxycholate- 16%
    Taurodeoxycholate – 8%
    Various lithocholate – 4%


                                                    Bile salts
 Detergent character of bile salts is due to the hydrophobic-hydrophilic
 nature of the molecules

 The presence of hydroxyl (or sulfate) and the terminal carboxyl group on
  the tail gives the molecule its hydrophilic face

 The steroid ring with its puckered plane provides the hydrophobic face

                    Function of bile salts
 Emulsification of fats due to detergent activity
 Aids in the absorption of fat-soluble vitamins (especially vitamin
  K)
 Accelerate the action of pancreatic lipase
 Choleretic action –stimulate the liver to secrete bile
 Stimulate intestinal motility
 Keep cholesterol in solution (as micelles)

				
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