Lipid Digestion and Absorption PDF

Digestion and absorption of lipid  DIETARY FAT COMPOSITION  More than 95% are triglycerides, the other are.  Cholesterol  Cholesterol esters  Phospholipids  Unesterified fatty acids. DIETARY SOURCES OF LIPIDS  Animal sources Dairy products , Meat, butter, fish, pork & e...

Digestion and absorption of lipid  DIETARY FAT COMPOSITION  More than 95% are triglycerides, the other are.  Cholesterol  Cholesterol esters  Phospholipids  Unesterified fatty acids. DIETARY SOURCES OF LIPIDS  Animal sources Dairy products , Meat, butter, fish, pork & eggs.  Vegetables sources Cooking oils ,sun flower oil, Mustard oil , Ground nut oil Fats from other vegetables sources.  Digestion in mouth  Hydrolysis of TAG is initiated by lingual lipase , which attack ester bond forming 1,2-diacylglycerols and free fatty acids. 1- Lingual lipase:  Acid-stable lipase.  Secreted by dorsal surface of tongue.  Active at low pH(2– 7.5) ,optimum pH 4 - 4.5  Ideal substrate-short chain TGS.  Milk fat contains short chain fatty acids which are esterified at -3 position, thus it is the best substrate for lingual lipase.  Enzymatic action continues in stomach.  Digestion in stomach 2-Gastric lipase :  Secreted by the gastric mucosa.  Digest TAG molecules, containing fatty acids of short- or medium-chain length (less than 12 carbons). Both enzymes play an important role in:  lipid digestion in neonates, for whom milk fat is the primary source of calories.  Individuals with pancreatic insufficiency, such as cystic fibrosis.  These enzymes aid patients with cystic fibrosis in degrading TAG molecules despite a near or complete absence of pancreatic lipase.  In the pancreas, the decreased hydration results in thickened secretions such that pancreatic enzymes are not able to reach the intestine, leading to pancreatic insufficiency. Treatment includes enzyme replacement therapy  Emulsification of dietary lipid in the small intestine  The emulsification of dietary lipids occurs in the duodenum  Lipids are hydrophobic, and thus are poorly soluble in the aqueous environment of the digestive tract.  Lipase enzyme is water soluble and can work only at the surface of lipid droplets.  TAG digestion occurs at lipid –water interfaces and the rate of digestion depends on surface area of this interface &emulsifying action of bile salts (which leads to increase the surface area of the hydrophobic lipid and the digestive enzymes can acts effectively). Emulsification is accomplished by 2 complementary mechanisms : 1. Use of the detergent properties of the bile salts [emulsifying agents interact with the dietary lipid particles and the aqueous duodenal contents, thereby stabilizing the particles as they become smaller, and preventing them from aggregation]. 2. Mechanical mixing due to peristalsis.  Degradation of dietary lipids by pancreatic enzymes Contents of pancreatic juice Pancreatic lipase, Phospholipase A2 & Cholesterol esterase(hydrolase) 1- TAG degradation:  Pancreatic lipase (esterase ) : preferentially removes the fatty acids at carbons 1 and 3.  The primary products of hydrolysis are mixture of 2-monoacylglycerol and free fatty acids.  Esterase found in high concentrations in pancreatic secretions, and it is highly efficient catalytically, thus only severe pancreatic deficiency , cystic fibrosis, results in significant malabsorption of fat.  Pancreatic Colipase: it causes a conformational change in the lipase that exposes its active site.[Note: Colipase is secreted as the zymogen, procolipase, which is activated in the 2- Cholesteryl ester degradation:  hydrolyzed by pancreatic cholesterol esterase ( or hydrolase) requires bile salts for optimum activity, which produces cholesterol plus free fatty acids. 3- Phospholipid degradation:  Pancreatic juice is rich in the proenzyme of phospholipase A2 that is activated by trypsin and requires bile salts for optimum activity.  Phospholipase A2 removes one fatty acid from carbon 2 of a phospholipid, leaving a lysophospholipid.  The remaining fatty acid at carbon 1 can be removed by lysophospholipase, leaving a glycerylphosphoryl base that may be excreted in the feces, further degraded, or absorbed  Control of lipid digestion A. Cholecystokinin (CCK) : small peptide hormone ,produced by cells in the mucosa of the jejunum and lower duodenum , in response to the presence of lipids and partially digested proteins entering these regions.  CCK acts on: - The gallbladder (causing it to contract and release bile). - The exocrine cells of the pancreas (causing them to release digestive enzymes). - The gastric motility, decreases gastric motility, resulting in a slower release of gastric contents into the small intestine. B. Secretin : small peptide hormone, produced in response to the low pH of the chyme entering the intestine.  Secretin causes the pancreas and the liver to release a watery solution rich in bicarbonate that helps neutralize the pH of the intestinal contents, bringing them to the appropriate pH for digestive activity by pancreatic enzymes.  Absorption of lipids by intestinal mucosal cells (enterocytes) - Free fatty acids, free cholesterol, and 2-monoacylglycerol are the primary products of lipid digestion in the jejunum. - These, plus bile salts and fat-soluble vitamins, form mixed micelles (they are soluble in the aqueous environment of the intestinal lumen). - These particles approach the primary site of lipid absorption, the brush border membrane of the enterocytes (mucosal cell). - The hydrophilic surface of the micelles facilitates the transport of the hydrophobic lipids through the unstirred water layer to the brush border membrane where they are absorbed. - Short- and medium-chain length fatty acids do not require the assistance of mixed micelles for absorption by the intestinal mucosa. Re- synthesis of TAG and cholesteryl esters.  The mixture of lipids absorbed by the enterocytes migrates to the endoplasmic reticulum where biosynthesis of complex lipids takes place.  Virtually all long-chain fatty acids entering the enterocytes are used to form TAGs, phospholipids, and cholesteryl esters.  Short- and medium-chain length fatty acids are not converted to their CoA derivatives, and are not re-esterified to 2 - monoacylglycerol.  Instead, they are released into the portal circulation, where they are carried by serum albumin to the liver.