bile acid.ppt.pptx

bile acid

1. DEPARTMENT OF BIOCHEMISTRY LUMBINI MEDICAL COLLEGE PRAVAS, TANSEN, NEPAL BILE ACIDS

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.

3. Structure of bile acids

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

8. BIOSYNTHESIS OF BILE ACIDS Conversion of Cholesterol to 7- α - hydroxycholesterol 7- α - hydroxylase , a microsomal enzyme Rate limiting reaction

9. 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 .

10. 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

11. The reaction/ steps for synthesis of bile acids are summerzed below:- Cholesterol hydroxylated at 3/7/12 position. Removal of 3 carbon unit, to make it 24C. Conjugation with glycine and taurine . Secretion into intestinal canal. In the intestine, deconjuagtion and removal of hydroxyl group.

12. (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 .

13. 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

14. (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

15. CLINICAL ASPECTS 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

16. 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

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