DIGESTION & ABSORPTION OF LIPIDS

FULL CHAPTER OF DIGESTION & ABSORPTION OF LIPIDS

1. Digestion & Absorption of lipids Gandham . Rajeev

2. The major dietary lipids are triacylglycerol, cholesterol & phospholipids The average normal Indian diet contains about 20-30 g of lipids/day Digestion in Stomach: The lingual lipase from the mouth enters stomach along with the food It has an optimum pH of 2.5-5 The enzyme active in the stomach

3. It acts on short chain triglycerides (SCT ) SCTs are present in milk, butter and ghee The action of lingual lipase is more significant in the newborns Gastric lipase: Gastric lipase is acid stable, with an optimum pH around 5.4 It is secreted by chief cells, the secretion is stimulated by gastrin . Upto 30 % digestion of triglycerides occurs in stomach

4. Emulsification of lipids in the small intestine : Emulsification is a prerequisite for digestion of lipids The lipids are dispersed into smaller droplets ; surface tension is reduced; and surface area of droplets is increased This process is favoured by: 1. Bile salts ( detergent action) 2. Peristalsis (mechanical mixing) 3. Phospholipids

5. Bile salts: The bile salts are sodium glycocholate & sodium taurocholate Bile salts are the biological detergents synthesized from cholesterol in the liver They are secreted with bile into the duodenum Bile salts possess steroid nucleus, the side chain is attached to either glycine ( glycocholic acid) or taurine ( taurocholic acid ) Bile salts are the most effective biological emulsifying agents

6. They interact with lipid particles and the aqueous duodenal contents and convert them into smaller particles (emulsified droplets ) The bile salts lower surface tension The emulsification increases the surface area of the particles for enhanced activity of enzymes

7. Surfactant action of degraded lipids: The initial digestive products of lipids ( catalysed by lipase), free fatty acids, monoacylglycerols promote emulsification These compounds along with phospholipids are known as surfactants Surfactants get absorbed to the water-lipid interfaces & increase the interfacial area of lipid droplets Mechanical mixing due to peristalsis also helps in the emulsification

8. Bile salts as emulsifying agents interact with the dietary lipid particles and the aqueous duodenal contents, thereby stabilizing the lipid particles as they become smaller Emulsification by bile salts

9. Digestion of lipids by pancreatic enzymes: The pancreatic enzymes responsible for the degradation of dietary TAGs, cholesteryl esters & phospholipids Digestion of Triglycerides: Pancreatic lipase hydrolyse the fatty acids esterified to the 1 st & 3 rd carbon atom of glycerol forming 2-monoacylglycerol & two molecules of fatty acid Isomerase shifts the ester bond from position 2 to 1 The bond in the 1 st position is then hydrolysed by the lipase to form free glycerol & fatty acid

10. The major end products of the digestion of TAG are 2-MAG (78%), 1-MAG (6%), glycerol and fatty acids (14 %) Co-lipase: It is a small protein molecule The activity of pancreatic lipase is inhibited by bile acids in the small intestine & this problem is overcome by colipase Also secreted by pancreas as pro- colipase & converted to active form by trypsin Colipase binds at the lipid-aqueous interface & helps to anchor & stabilize lipase

11. Complete hydrolysis of triglyceride In the intestines, generally fats are only partially hydrolysed

12. Emulsification & digestion of TAGs

13. Lipid esterase: It is a less specific enzyme present in pancreatic juice lt acts on monoacylglycerols , cholesteryl esters, vitamin esters etc. to liberate free fatty acids The bile acid is essential for the activity of lipid esterase Degradation of cholesteryl esters: Pancreatic cholesterol esterase ( cholesteryl ester hydrolase ) cleaves cholesteryl esters to cholesterol & free fatty acids

14. Physiologically important lipases Lipase Site of action Preferred substrate Product(s) Lingual / acid stable lipase Mouth , stomach TAGS with medium chain FAS FFA+DAG Pancreatic lipase + co-lipase Small intestine TAGS with long chain FAS FFA+2MAG Intestinal lipase with bile acids Small intestine TAGS with medium chain FAS 2FFA+glycerol Phospholipase A2 + bile acids Small intestine PLs with unsat . FA at position 2 Unsat FFA lysolecithin Lipoprotein lipase insulin (+) Capillary walls TAGs in chylomicron or VLDL FFA+ glycerol Hormone sensitive lipase Adipose cell TAG stored in adipose cells FFA+ glycerol

15. Degradation of phospholipids: Phospholipases are enzymes responsible for the hydrolysis of phospholipids Pancreatic juice is rich in phospholipase A 2 which cleaves the fatty acid at the 2 nd position of phospholipids The products are a free fatty acid and a lysophospholipid Phospholipase A2 is secreted as a zymogen which is activated in the intestine by the action of trypsin

16. Phospholipid Degradation

17. Absorption of lipids: Lipolytic theory put forth by Verzar : According to this, fats are completely hydrolysed to glycerol & FFA These are absorbed either as soaps or in association with bile salts Partition theory proposed by Frazer: According to this, digestion of TAGs is partial & not complete The partially digested TAGs in association with bile salts, form emulsion L ipids are taken up by the intestinal mucosal cells

18. Bergstrom theory: Long chain fatty acids (>14 carbons) are absorbed to the lymph & not directly to the blood Mixed Micelle Formation: The products of digestion are 2-monoglycerides , long chain fatty acids, cholesterol , phospholipids and lysophospholipids are incorporated into molecular aggregates to form mixed micelle Micelles are spherical particles with a hydrophilic exterior & hydrophobic interior core

19. Miscellar formation

20. Due to detergent action , the bile salts help to form micellar aggregates Micellar formation is essential for the absorption of fat-soluble vitamins such as vitamin A , D, E and K The micelles are aligned at the microvillous surface of the jejunal mucosa Fatty acids , 2-MAG and other digested products passively diffuse into the mucosal cell

21. Synthesis of lipids in intestinal mucosal cells: The fatty acids of short & medium chain length (<10 carbons ), after their absorption into the intestinal cells, do not undergo any modification They enter the portal circulation & are transported to the liver in a bound form to albumin

22. Re-esterification Inside the Mucosal Cell: Inside the intestinal mucosal cell, the long chain fatty acids are re-esterified to form triglycerides The fatty acids are first activated to fatty acyl CoA by the enzyme, acyl CoA synthetase or thiokinase & requires energy Two, such activated FAS react with monoacyl glycerol (MAG) to form the triglyceride Majority of molecules follow this MAG pathway

23. Free glycerol absorbed from intestinal lumen directly enters into the blood stream Free glycerol is not available for re-esterification But the cells can convert glucose to glycerol phosphate & add 3 molecules of acyl groups to synthesize TAG

24. Absorption of fat as chylomicrons

25. Absorption of fatty acids Long chain fatty acids are absorbed into the intestinal cell wall, they are re-esterified, made into chylomicrons & enter into lymphatics Short chain fatty acids are directly absorbed into blood capillaries Bile acids are reabsorbed into portal vein

26. Chylomicrons: The lipids that are resynthesized in the intestinal cells are hydrophobic in nature They are put together as lipid droplets and surrounded by a thin layer consisting of mostly apolipoproteins (A1 and B-48) & phospholipids This package of lipids enveloped in the layer stabilizes the droplets and increases their solubility These particles are known as chylomicrons

27. Chylomicrons migrate to the plasma membrane of intestinal mucosal cells They are released into the lymphatic vessels by exocytosis The presence of chylomicrons (Greek ; chylos -juice) gives the lymph a milky appearance , observed after a lipid-rich meal Chylomicrons enter the large body veins via the thoracic duct Blood from here flows to the heart & then to the peripheral tissues (muscle , adipose tissue) & finally , to the liver

28. Formation & transport of chylomicrons

29. Size: 0.1–1 µm Average composition TG (84 %) Cholesterol(2%) Ester Cholesterol (4 %) Phospholipid (8 %) Apo lipoproteins (2%) Formation & transport of chylomicrons

30. Transport & utilization of chylomicrons

31. Clinical significance of Chylomicron synthesis & utilization Defective synthesis- Due to deficiency of apo -B 48 protein. The triglyceride may accumulate in intestinal cells. Chyluria - Due to an abnormal connection between urinary tract & lymphatic drainage system of the intestines , forming Chylous fistula. Characterized by passage of Milky urine.

32. Chylothorax - There is an abnormal connection between pleural space and the lymphatic drainage of small intestine resulting in accumulation of lymph in pleural cavity giving Milky pleural effusion Absorption of short chain fatty acids: Short chain fatty acids ( SCFA) & medium chain fatty acids ( MCFA) do not need re-esterification They can directly enter into blood vessels, then to portal vein , finally to liver where they are immediately utilised for energy Their absorption is rapid

33. Abnormalities in lipid digestion & Absorption: Defective digestion: In steatorrhea , daily excretion of fat in feces is >6 g/day It is due to chronic diseases of pancreas In such cases , unsplit fat is seen in feces Defective absorption: I f the absorption alone is defective , most of the fat in feces may be split fat, i.e. fatty acids and monoglycerides Celiac disease

34. Surgical removal of intestine Obstruction of bile duct: Due to gall stones , tumors of head of pancreas , enlarged lymph glands, etc. The result is deficiency of bile salts. TAGs with short chain and medium chain fatty acids are digested & absorbed properly , they do not require micellerisation for absorption

35. Chyluria : There is an abnormal connection between the urinary tract & lymphatic drainage system of the intestine . Urine appears milky due to lipid droplets Chylothorax can result from an abnormal connection between the pleural cavity and thoracic duct Fate of Chylomicrons: The absorbed (exogenous) TAGs are transported in blood as chylomicrons & taken up by adipose tissue & liver

36. Liver synthesizes endogenous triglycerides These are transported as VLDL & are deposited in adipose tissue During starvation states, TAGs in adipose tissue are hydrolyzed to produce free fatty acids In the blood, they are transported , complexed with albumin These free fatty acids are taken up by the cells & are then oxidised to get energy

37. Reference books Textbook of Biochemistry - Dr.U.Satyanarayana Textbook of Biochemistry - DM.Vasudevan Textbook of Medical Biochemistry - MN Chatterjea

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