Lec. 4: Digestion of Lipids PDF

Lec.4: Digestion of Lipids Lec. 4 : Digestion of Lipids ‫الصفحة‬1  Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic molecules that can be extracted from tissues by nonpolar solvents , Because of their insolubility in aqueous solutions, body lipids are generally...

Lec.4: Digestion of Lipids Lec. 4 : Digestion of Lipids ‫الصفحة‬1  Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic molecules that can be extracted from tissues by nonpolar solvents , Because of their insolubility in aqueous solutions, body lipids are generally found compartmentalized, as in the case of membrane-associated lipids or droplets of triacylglycerol in white adipocytes, or transported in plasma in association with protein, as in lipoprotein particles or albumin. The major dietary lipids are triacylglycerol, cholesterol and phospholipids. The average daily intake of lipids by U.S. adults is about 81 g, of which more than 90% is normally triacylglycerol (TAG, formerly called triglyceride). The remainder of the dietary lipids consists primarily of cholesterol, cholesteryl esters, phospholipids, and unesterified (―free‖) fatty acids. 1/ digestion of lipids begins in the stomach, catalyzed by relatively acid stable enzymes , with pH optimums of pH 4 to pH 6,―acid lipases‖ acidstable lipase (lingual lipase) that originates from glands at the back of the tongue. The primary target of this enzyme are TAG molecules, particularly those containing fatty acids of short- or medium-chain length (fewer than 12 carbons, such as are found in milk fat), So that the action of lingual lipase is observed to be more significant in the newborn infants. These same TAGs are also degraded by a separate gastric lipase, secreted by the gastric mucosa the secretion is stimulated by Gastrin. Lec. 4 : Digestion of Lipids ‫الصفحة‬2 2/ Dietary lipid in the small intestine The critical process of emulsification of dietary lipids occurs in the duodenum. Emulsification is a pre-requisite for digestion of lipids. The lipids are dispersed into smaller droplets so that the digestive enzymes can act effectively; surface tension is reduced; and surface area of droplets is increased. This process is favored by: 1. Bile salts (detergent action lower surface tension) 2. Peristalsis (mechanical mixing) 3. Lipolytic Enzymes( Pancreatic lipase with co-lipase , Cholesterol esterase and Phospholipase A2) 3/Degradation of dietary lipids by pancreatic enzymes The bile (pH 7.7) entering the duodenum serves to neutralize the acid chyme from the stomach and provides a pH favorable for the action of pancreatic enzymes. The dietary TAG, cholesteryl esters, and phospholipids are enzymically degraded (―digested‖) by pancreatic enzymes 1. TAG molecules are too large to be taken up efficiently by the mucosal cells of the intestinal villi. They are, therefore, acted upon by an esterase, pancreatic lipase, which preferentially removes the fatty acids at carbons 1 and 3. The primary products of hydrolysis are thus a mixture of 2- monoacylglycerol and free fatty acids. and it is highly efficient catalytically, thus insuring that only severe pancreatic deficiency, such as that seen in cystic fibrosis, results in significant malabsorption of fat. A second protein, colipase, also secreted by the pancreas, as the zymogen, (procolipase), which is activated in the intestine by trypsin. NOTE: Orlistat, an antiobesity drug, inhibits gastric and pancreatic lipases, thereby decreasing fat absorption, resulting in loss of weight Lec. 4 : Digestion of Lipids ‫الصفحة‬3 2. Cholesteryl ester degradation: Most dietary cholesterol is present in the free (nonesterified) form, with 10–15% present in the esterified form. Cholesteryl esters are hydrolyzed by pancreatic cholesteryl ester hydrolase (cholesterol esterase), which produces cholesterol plus free fatty acids 3. Phospholipase A2 produces lysophospholipid and a fattyacid TABLE 12.1: Physiologically important lipases lipases Site of action Preferred substrate Product(s) Lingual/acidstable lipase Mouth, stomach TAGs with short and FFA+DAG medium chain FAs Pancreatic lipase + small intestine TAGs with longchain FFA+2MAG colipase FAs Intestinal lipase with bile small intestine TAGs with medium 3 FFA+ glycerol acids chain FAs Phospholipase A2 + bile small intestine PLs with unsat. FA on Unsat FFA acids position 2 Lipoprotein lipase capillary walls TAGs in chylomicron FFA+ glycerol or VLDL Hormone sensitive lipase adipocytes TAG stored in adipose FFA+ DAG tissue Lec. 4 : Digestion of Lipids ‫الصفحة‬4 Short- and mediumchain length fatty acids do not require the assistance of mixed micelles for absorption by the intestinal mucosa. Long chain fatty acids (chain length more than 14 carbons) are absorbed to the lymph and not directly to the blood. Mixed Micelle Formation i. The products of digestion in the jejunum are 2 monoacylglycerols, long chain fatty acids, free cholesterol, phospholipids and lysophospholipids These, plus bile salts and fat-soluble vitamins (A, D, E, and K), form mixed micelles—The micelles are spherical particles with a hydrophilic exterior and hydrophobic interior core. Due to their amphipathic nature, the bile salts help to form micellar aggregates. These particles approach the primary site of lipid absorption, the brush border membrane of the enterocytes (mucosal cell). Bile salts are absorbed in the ileum. Lec. 4 : Digestion of Lipids ‫الصفحة‬5 Re-esterification Inside the Mucosal Cell i. The mixture of lipids absorbed by the intestinal mucosal cell, migrates to the endoplasmic reticulum where biosynthesis of complex lipids takes place, the long chain fatty acids are re-esterified to form triacylglycerols ii. Free glycerol absorbed from intestinal lumen directly enters into the bloodstream. So free glycerol is not available for re-esterification. But the cells can derive glycerol phosphate from glucose by glycolysis, and add 3 molecules of acyl groups to synthesize TAG. SCFA Absorption Short chain fatty acids (SCFA) (seen in milk, butter, ghee) and medium chain fatty acids (MCFA) (in coconut oil and mother's milk) do not need re- esterification. They can directly enter into blood vessels, then to portal vein, finally to liver where they are immediately utilized for energy. Their absorption is rapid. They are better absorbed than long chain fatty acids Chylomicrons Formation The newly resynthesized TAGs and cholesteryl esters are very hydrophobic, and aggregate in an aqueous environment. It is, therefore, necessary that they be packaged as particles of lipid droplets surrounded by a thin layer composed of phospholipids, un-esterified cholesterol, and a molecule of the characteristic protein, apolipoprotein B-48.This layer stabilizes the particle and increases its solubility The particles are released by exocytosis from enterocytes into the lacteals (lymphatic vessels originating in the villi of the small intestine). The presence of these particles in the lymph after a lipid- rich meal gives it a milky appearance. This lymph is called chyle and the particles are named chylomicrons. Chylomicrons follow the lymphatic Lec. 4 : Digestion of Lipids ‫الصفحة‬6 system to the thoracic duct, and are then conveyed to the left subclavian vein, where they enter the blood Fate of Chylomicrons i. Use of dietary lipids by the tissues : The absorbed (exogenous) triglycerols are transported in blood as chylomicrons. They are taken up by adipose tissue, skeletal muscle and liver. Triacylglycerol in chylomicrons is broken down primarily in the capillaries of skeletal muscle and adipose tissues, but also those of the heart, lung, kidney, and liver. Triacylglycerol in chylomicrons is degraded to free fatty acids and glycerol by lipoprotein lipase. ii. The free fatty acids may either directly enter adjacent muscle cells or adipocytes, or they may be transported in the blood in association with serum albumin until they are taken up by cells. iii. Adipocytes can also re-esterify free fatty acids to produce TAG molecules, which are stored until the fatty acids are needed by the body iv. Glycerol that is released from TAG is used almost exclusively by the liver to produce glycerol 3-phosphate, which can enter either glycolysis or gluconeogenesis v. Liver synthesizes endogenous triglycerols. These are transported as VLDL (very low density lipoproteins) and are transported to adipose tissue. Lec. 4 : Digestion of Lipids ‫الصفحة‬7 vi. After most of the TAG has been removed, the chylomicron remnants (which contain cholesteryl esters, phospholipids, apolipoproteins, fat-soluble vitamins, and some TAG) bind to receptors on the liver and are then endocytosed. Main Six steps of lipid absorption 1. Minor digestion of triacylglycerols in mouth and stomach by lingual (acid-stable) lipase 2. Major digestion of all lipids in the lumen of the duodenum/ jejunum by pancreatic lipolytic enzymes 3. Bile acid facilitates formation of mixed micelles 4. Passive absorption of the products of lipolysis from the mixed micelle into the intestinal epithelial cell 5. Re- esterification of 2-monoacylglycerol with free fatty acids inside the intestinal enterocyte 6. Assembly of chylomicrons containing Apo B48, triacylglycerols, cholesterol esters and phospholipids and export from intestinal cells to the lymphatics. SUMMARY The digestion of dietary lipids begins in the stomach and continues in the small intestine, The hydrophobic nature of lipids that contain long-chain length fatty acids (LCFA) be emulsified for efficient degradation. Triacylglycerols (TAG) obtained from milk contain short to medium chain length fatty acids that can be degraded in the stomach by the acid lipases (lingual lipase and gastric lipase). Cholesteryl esters (CE), phospholipids (PL), and TAG containing LCFAs are degraded in the small intestine by enzymes secreted by the pancreas. These enzymes are pancreatic lipase, phospholipase A2, and cholesteryl esterase. The dietary lipids are emulsified in the small intestine using peristaltic action, and bile salts, which serve as a detergent. The primary products from enzymatic degradation of dietary lipid are 2-monoacylglycerol, unesterified cholesterol, and free fatty acids. These compounds, plus the fat-soluble vitamins, form mixed micelles that facilitate the absorption of dietary lipids by intestinal mucosal cells (enterocytes).These cells resynthesize TAG, CE, and PL, and also synthesize protein (apolipoprotein B-48), all of which with the fat soluble vitamins form chylomicrons released into the lymph, carried to the blood. Short and medium chain fatty acids enter blood directly. [Problems with fat absorption cause steatorrhea. Lec. 4 : Digestion of Lipids ‫الصفحة‬8  They are a group of molecular complexes found in the blood plasma of mammals.  Plasma lipoproteins transport lipid molecules (Triacylglycerols, phospholipids, and cholesterol) through the blood stream from one organ to another.  The protein components of lipoproteins are called apolipoproteins or apoproteins Lipoprotein particle contents. 1. Inner core-hydrophobic. a. Cholesterol esters. b. Triglycerides. 2. Outer surface-amphipathic. a.Amphipathic phospholipids. b.Free- cholesterol. c. Apoproteins. Distribution of lipoproteins In certain oragans e.g. a. In the lung tissue: It is regarded as thromboplastic protein. b. In the eye (layer of rods in the retina) rhodopsin is a lipoprotein. c. In the blood: Most of the blood lipids are carried as lipoprotein complexes. The lipid fraction in such complexes may be: Triglycerides, phospholipids, cholesterol (free or esterified), Fat - soluble vitamins and steroid hormones. - The protein fraction in such complexes may be: α1-globulin or 1-globulin Lec. 4 : Digestion of Lipids ‫الصفحة‬9 Classification of lipoproteins; depends on their density; Lipoproteins can be classified into 6 types: 1. Chylomicrons – large lipoproteins, low density, formed in the mucosal cells of intestine, used in transport of dietary triglycerides and cholesterol ester from intestine to tissues. Lec. 4 : Digestion of Lipids ‫الصفحة‬10 2. VLDL -Very low density lipoproteins (VLDL or pre β-lipoproteins). synthesized in the liver, responsible for transport of lipids to the tissues, triglyceride rich. 3. IDL – triglycerides and cholesterol. 4. LDL – Low density lipoproteins (LDL or β -lipoproteins).they are products of VLDL, they carry cholesterol to the tissues to be used for the synthesis of cell membranes, steroid hormones, and bile salts. Note: When the level of LDL exceeds the amount of cholesterol needed by the tissues, the LDLs deposit cholesterol to the arteries, which can restrict blood flow and increase the risk of developing heart disease and for myocardial infarctions (heart attacks). This is why LDL cholesterol is called "bad" cholesterol. Lec. 4 : Digestion of Lipids ‫الصفحة‬11 5. HDL – High density lipoproteins (HDL or α -lipoproteins).produced in the liver, remove excess cholesterol from the tissues and carry it to the liver where it is converted to bile salts and eliminated. Note: When HDL levels are high, cholesterol that is not needed by the tissues is carried to the liver for elimination rather than deposited in the arteries, which gives the HDLs the name of "good" cholesterol. Because high cholesterol levels associated with the onset of atherosclerosis and heart disease, the serum levels of LDL and HDL are generally determined in a medical examination. A lower level of serum cholesterol decreases the risk of heart disease. Higher HDL levels are found in people who exercise regularly and eat less saturated fat. Lec. 4 : Digestion of Lipids ‫الصفحة‬12