Lipid Chemistry Lecture PDF

Lippincott’s illustrated reviews Chapter 15 – Page 173 Lecture 25 Lipid Chemistry 1  Specific Objectives By the end of this lecture students can be able to: Explain the digestive pathway of lipids. Discuss the hormonal regulation of lipid digestion....

Lippincott’s illustrated reviews Chapter 15 – Page 173 Lecture 25 Lipid Chemistry 1  Specific Objectives By the end of this lecture students can be able to: Explain the digestive pathway of lipids. Discuss the hormonal regulation of lipid digestion. Understand the reason for cystic fibrosis. 2  OVERVIEW different from each other Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic molecules that can be extracted from tissues by nonpolar solvents. 3  They found as membrane-associated lipids or droplets of triacylglycerol in white adipocytes, or transported in plasma in association with protein, as in lipoprotein particles, or on albumin. Sites 4 Function: not the First But Lipids are a major source of energy for the body. Sepaute them Provides the hydrophobic barrier that permits partitioning of the aqueous contents of cells and subcellular structures. intracelluer and extracelluer Some fat-soluble vitamins have regulatory or coenzyme functions. vitamin A E D K Estroge Testosvon Prostaglandins and steroid hormones play major roles in the control of the body’s homeostasis. cant Imbalances of lipid metabolism can diseases lead to atherosclerosis and obesity. 5  Digestion of Lipids Dietary lipid consists of more than 90% triacylglycerol (TAG, formerly called triglyceride). Glycerol with 3 Fatty at The remainder of the dietary lipids consists primarily of cholesterol, Free acid cholesteryl esters, Fatty phospholipids, and cell membrane unesterified (“free”) fatty acids. 6 A. Processing of dietary lipids in the stomach The digestion of lipids begins in the stomach, catalyzed by: when swolling it get secreted lingual lipase that originates from glands at the back of the tongue. does not work in month needs 11 Gastric lipase, secreted by the gastric mucosa. Important in newbor Both enzymes are relatively acid- stable, with pH optimums of pH 4 to pH 6. Break down of EEE of They hydrolyze TAG molecules containing fatty acids of short- or medium-chain length (fewer than 12 carbons, such as are found in milk fat). medium 7 12  n 9 EEnd 8 I  These “acid lipases” play a particularly important role in lipid digestion in neonates, for whom milk fat is the primary source of calories. They also become important digestive enzymes in individuals with pancreatic insufficiency, such as those with cystic fibrosis. 9 Cystic fibrosis (CF): Autosomal recessive disorder that caused by mutations to the gene for the CF transmembrane conductance regulator (CFTR) protein that functions as a chloride channel on epithelium. Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water. 10  make cholride channel From inside to outside which is negativ which will increase the negative causing Na to pass Passivly making Nacl salt needing water Passing all outside see when there's defect cholinde and NA water will cell stay inside causing thickness 11  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. 12  Treatment includes replacement of these enzymes, supplementation with fat-soluble vitamins as vitamin D and water-soluble vitamins, which include vitamin C and the B-complex vitamins, folic acid, biotin, and pantothenic acid. Note: CF also causes chronic lung infections with progressive pulmonary disease. treat m it isn't In cystic fibrosis and other chronic lung disease vitamin D improves airway remodeling in response to injury, decreases airway inflammation, and decreased airway bacterial colonization. 13 B. Emulsification of dietary lipid in the duodenum Large fat globule Emulsification increases the surface area of the hydrophobic lipid droplets. by gathering around it breaking it to small Bile salts act as emulsifying agents, made in the liver and stored 14 in the gallbladder, are derivatives of cholesterol. Triglycerides cholesterol ester Phosphlipid Most important enzyme pancreatic lipase 15 C. Degradation of dietary lipids by pancreatic enzymes 1. TAG degradation: Pancreatic lipase, 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. 16  Colipase, also secreted by the pancreas, binds the lipase at a ratio of 1:1, and anchors it at the lipid- aqueous interface. making the pancreatic lipase stick to droplet Colipase restores activity to lipase in the presence of inhibitory substances like bile acids that bind the micelles. Orlistat, an antiobesity drug, inhibits gastric and pancreatic lipases, thereby decreasing fat absorption, resulting in loss of weight. 17 2. Cholesteryl ester degradation: Most dietary cholesterol is present in the free (nonesterified) form, with 10–15% present in the esterified form. Easter bond Fatty acid Cholesteryl esters are hydrolyzed by pancreatic cholesteryl ester hydrolase (cholesterol esterase), which produces cholesterol plus free fatty acids. will activate Cholesteryl ester hydrolase activity is greatly increased in the presence of bile salts. 18 19 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. Activated by trypsin 3 s 82141 20 21  4. Control of lipid digestion: Cells in the mucosa of the lower duodenum and jejunum produce a small peptide hormone, cholecystokinin (CCK), in response to the presence of lipids. Function cholecystokinin acts on the gallbladder (causing it to contract and release bile), and on the exocrine cells of the pancreas (causing them to release digestive enzymes). 22  secutetin Acidity cholecytokinin lipid 23  Other intestinal cells produce another small peptide hormone, secretin. Activated by acid ph Secretin causes the pancreas and the liver to release a solution rich in bicarbonate that helps neutralize the pH of theTakeitalkaline or close to it intestinal contents. 24 D. 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 (A, D, E, and K), form mixed micelles 25  Mixed micelles are—disk shaped clusters of amphipathic lipids with their hydrophobic groups on the inside and their hydrophilic groups on the outside. C means that has hydrophobic and hydrophilic together These soluble in the aqueous environment of the intestinal lumen. These particles absorbed by the brush border membrane of the enterocytes (mucosal cell). 26 27  F. Lipid malabsorption Lipid malabsorption, resulting in increased lipid including the fat soluble vitamins and essential fatty acids, in the feces which called steatorrhea. Steatorrhea can be caused by disturbances in lipid digestion and/or absorption. Such disturbances can result from several conditions, including CF (causing poor digestion) and shortened bowel (causing decreased absorption). 28 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 29