L3 Biochemical Aspects of Lipid Digestion PDF

L3: Biochemical aspects of digestion of lipids GNT Block Color Index: • • • • • • Main text Female slides Male slides Important Doctor’s notes Extra notes Editing file: Objectives: Understand the process of digestion of dietary lipids including, the organs involved, the enzymes required, and t...

L3: Biochemical aspects of digestion of lipids GNT Block Color Index: • • • • • • Main text Female slides Male slides Important Doctor’s notes Extra notes Editing file: Objectives: Understand the process of digestion of dietary lipids including, the organs involved, the enzymes required, and the end products. Study the synthesis, secretion and fate of chylomicron Understand the clinical manifestations of diseases that involve defective lipid digestion and/or absorption (indigestion and malabsorption syndrome) Lecture presented by : Dr. Sumbul Fatma Science Bites Dr. Usman Ghani Ninja Nerd Dietary lipids Dietary lipid: organs and enzyme Lipid degradation by the pancreatic enzymes Lipid digestion in the stomach and intestine Overview Lipid absorption, re-synthesis and secretion. 439: Lipid molecules are hard to absorb so the body breaks them down to smaller molecules, absorbs them then rebuilds the molecules. Control of lipid digestion Pancreatic insufficiency Lipid malabsorption Use of dietary lipid by the tissues Dietary lipids Dietary lipids intake is ~78-81 g/day. Triacylglycerol is >90%, The remainder includes: Cholesterol, Cholesterol Ester 439: There is fatty acid bonded to the cholesterol molecule , Phospholipids, Glycolipids and Free fatty acids. For lipids, digestion begins when they reach the stomach. However, the amount of lipids digested in the stomach is minimal. The majority of the digestion occurs in the small intestine and is completed there. Stomach 1.Lingual lipase. This enzyme is secreted in the mouth, but it starts working in the stomach because it needs an acidic medium to work. 2.Gastric lipase. Organs &Enzymes: Small intestine 1.Pancreatic Lipase / C0-lipase. 2.Cholesterol esterase. 3.Phospholipase A2. 4.Lysophospholipase. They are produced in the pancreas, but their main function is in the small intestines. Extra note: ● lipase plays a crucial role in lipid digestion by breaking down triglycerides into fatty acids and glycerol. ● Co-lipase aids lipase in this process by enhancing its activity. ● Cholesterol esterase is responsible for hydrolyzing cholesterol esters into free cholesterol and fatty acids. ● Phospholipase A2 acts on phospholipids, breaking them down into lysophospholipids and free fatty acids. ● Lysophospholipase further contributes by converting lysophospholipids into glycerophospholipids and fatty acids Lipid digestion In Stomach In Small intestine ● Catalyzed by an acid-stable lipase Emulsification: breaking down big lipid droplets into (lingual lipase & gastric lipase) 439: Acid smaller ones in an aqueous medium which increases the surface area. stable means that the enzyme doesn’t get denatured in an acidic environment like the stomach. ● Triacylglycerols (TAGs) are hydrolyzed (They will hydrolyze the TAGs which have short to medium chain fatty acids (12 carbon atoms or less).) by the lipases secreted under the tongue and gastric mucosa ● Acid lipases are important for lipid (milk fat is full of short and medium chain fatty acids) digestion in: -neonates Their primary food is milk. -patients with pancreatic insufficiency pancreatic secretions are either not produced or fail to reach the small intestine. ● Occurs in the duodenum ● Increases surface area of lipid droplets ● To maximize the effect of digestive enzymes Let's imagine the enzyme and fat like the water (enzyme) and oil (fat). We need a spoon to mix them (mechanical mixing) and also we need a detergent (bile salts) because Bile salt and phospholipids are amphipathic which means they have two ends, hydrophilic and hydrophobic that will make lipids (hydrophobic) available for the enzyme (hydrophilic) -Two mechanisms: 1-Detergent properties of bile salts in the bile (bile salts emulsify dietary lipid particles) 2-Mechanical mixing by peristalsis Extra By Pancreatic enzymes TAG degradation: ● Performed by pancreatic lipase, colipase. if somebody asks you which enzyme cleaves the fatty acid groups from the triacylglycerol, it is pancreatic lipase. But pancreatic lipase requires co-lipase for the activity of pancreatic lipase. ● Removes fatty acids at C1 and C3 ● Leaving 2-monoacylglycerol and free acids (FFAs) Pancreatic lipase: ● Found in high conc. In pancreatic secretion (2-3% of total proteins) ● It is inhibited by Orlistat, an antiobesity drug (so lipids are not digested; instead they are excreted with stool, causing fatty stools). Cholesteryl ester degradation: ● Hydrolyzed by cholesterol esterase ● Produces cholesterol + FFAs Digestion of Phospholipids(PL) Doctor's note: - Phospholipase A2 removes one fatty acid from the phospholipid and we get lysophospholipid - Lysophospholipase acts on lysophospholipids to give us glycerophosphoryl base which can be excreted Example of phospholipid digestion: - Phosphatidylcholine → Lysophosphatidylcholine →choline - Excreted in feces - Degraded - Or Absorbed IMPORTANT Doctor's note: In the digestive process, dietary lipids undergo minimal changes in the stomach; only short and medium-chain fatty acids are removed. In the small intestine, bile salts emulsify lipids, and pancreatic enzymes break them down into free fatty acids, 2-monoacylglycerol, and cholesterol. The remaining pieces of phospholipid, which consist of a glycerophosphoryl base, are excreted. These primary products are taken up by enterocytes, where they undergo reesterification, get repackaged as chylomicrons, and are transported via the lymphatic system. For Triacylglycerols you need pancreatic lipase & co-lipase. For cholesterol esters you need cholesterol esterase. For phospholipids, you need two enzymes, phospholipase A2 and lysophospholipase. Pancreatic insufficiency in cystic fibrosis (CF) CF is due to genetic mutations in CFTR (transmembrane conductance regulator protein) Functions as chloride channel on epithelium. The normal function of CFTR gene is increases the secretion of Chloride from epithelial cells, once the secretion of cl- increased from epithelial cells the Sodium reabsorption will decrease Defective CFTR causes: Decreased secretion of chloride & Increased reabsorption of sodium and water. Then water goes inside the epithelial cells which means pancreatic secretions now have less water available for them which means… Decreased hydration in pancreas thickens the pancreatic secretions When they become thick they go and block the pancreatic duct. (Pancreas secretion becomes paste like Pancreatic enzymes are unable to reach the intestine. Because Pancreatic duct is blocked. Which causes malnutrition and fatty stool. And this is called Pancreatic insufficiency. Treatment: enzyme and fat-soluble vitamin supplementation. 1- Because enzymes can’t reach the intestine. 2- Because fat soluble vitamins also get affected. Control of lipid digestion Controlled by hormones: Important 1. Cholecystokinin (CCK): - Acts on gallbladder to release bile. - Acts on pancreas to release enzymes. - Decreases gastric motility (slow release of gastric contents). (If you have undigested food already in the small intestine, you do not want stomach to be pushing more and more food into the small intestine because then the digestion process is going to be less efficient) 2. Secretin: - Low pH stimulates its secretion. When acidic chyme from the stomach enters the duodenum, it stimulates the release of secretin. - Acts on pancreas to release bicarbonate and liver to release bile. - Neutralizes the PH of the contents before entering the small intestine. Lipid absorption by enterocytes Products of lipid digestion (FFAs, free cholesterol, 2-monoacylglycerol) combine with bile salts and fat-soluble vitamins They form mixed micelles (disk-shaped particles). It's composed of Products of lipid digestion+ bile salts +fat-soluble vitamins Mixed micelles are hydrophobic inside and hydrophilic outside.(Amphipathic) Absorbed by brush border membrane of enterocytes. Because the cell membrane is amphipathic with the hydrophilic side out. Short and medium chain length fatty acids are absorbed directly. (They are water soluble, they do not require the assistance of mixed micelles for absorption by the intestinal mucosa). Resynthesis of TAG/Cholesterol esters Digested lipids absorbed by enterocytes migrate to endoplasmic reticulum for complex lipid biosynthesis 1. 2. Fatty acids Fatty acyl CoA 2-Monoacylglycerols TAGs You should know the names of the enzymes 2 1 3 3. Chylomicrons Assembly of chylomicrons by enterocytes Newly synthesized TAG and cholesterol ester are packaged as lipid droplets surrounded by a thin layer of: 1- Apolipoprotein B-48 (apo B-48) 2- Phospholipids 3- Free cholesterol Secretion of chylomicrons by enterocytes - By exocytosis into lymphatic vessels around villi of small intestine (lacteals) which enter into systemic circulation. - Serum becomes milky after a fatty meal. Lipid malabsorption Increased excretion of lipids, fat-soluble vitamins and essential FAs in the feces. Due to defects in lipid digestion or absorption Can be caused by CF or shortened bowel Key concepts for digestion and absorption of dietary lipids #439-Extra The big picture: Dietary lipids intake (e.g. TAGs and Cholesteryl esters) ↓ Digested and broken down in intestines by pancreatic enzymes ↓ Absorbed as mixed micelles in intestinal cells (enterocytes) ↓ Resynthesis of TAGs and Cholesteryl esters in ER of enterocytes ↓ Exocytosis into lymphatic vessels as Chylomicrons (lipoprotein) ↓ Chylomicrons circulating in blood (milky appearance) CVS recap: Function of chylomicrons? Transport dietary TAGs to peripheral tissues / and cholesterol to the liver (hepatocytes) | Take home massages Lipid digestion begins in stomach Emulsification of lipids occurs in duodenum, helped by peristalsis and bile salts Intestinal digestion of lipids by pancreatic enzymes Lipid absorption by mixed micelles Re-synthesis of TAGs, cholesterol ester and PLs inside the intestinal mucosal cells Assembly and secretion of chylomicrons into lymphatic lacteals and then into systemic circulation Quiz MCQs Q1: Which enzyme is responsible for the hydrolysis of triglycerides? A- Amylase B- Protease C- Pancreatic Lipase D- Gastric Lipase Q4: Where is the primary site for the absorption of the end products of lipid digestion? A- Stomach B- Small intestine C- Colon D- Esophagus Q2: Where does emulsification of dietary fats primarily occur? Q5: In lipid digestion,what is the primary function of phospholipase A2? A- Jejunum B- Stomach C- Duodenum D- Ileum A- Hydrolyzing cholesterol esters B- Activating pancreatic lipase C- Breaking down phospholipids D- Emulsifying lipids Q3: Chylomicrons are synthesized in which organ? Q6:Which organ secretes cholesterol esterase? A- Liver B- Pancreas C- Stomach D- Small intestine A- Liver B- Gallbladder C- Small intestine D- Pancreas Answers: 1-C, 2-C, 3-D, 4-B, 5-C, 6-D SAQ Q: How are the products of lipid digestion absorbed by enterocytes? A: They combine with bile salts and fat-soluble vitamins to form mixed micelles. These micelles are absorbed by the brush border membrane of enterocytes in the small intestine. Q: What is the role of cholecystokinin (CCK) in the control of lipid digestion? A: Cholecystokinin (CCK) acts on the gallbladder to release bile and on the pancreas to release enzymes. It also decreases gastric motility, resulting in the slow release of gastric contents. Members board Team Leaders Raghad Alhamid Remas Aljeaidi Mohammed Alqutub Team Members Leen Alduaij Zeyad Alotaibi Sultan Almishrafi Wafa Alakeel Mohammed Alarfaj Juwan Al Musma Madawi Alhussain Nazmi A Alqutub Wasan Alanazi Leen K Althunayan Faisal Alshowier Aishah boureggah Dana A Alkheliwi Osama Almashjari Mansour Alotaibi Aldanah Abdullah Nazmi M Alqutub Salma Alsaadoun Layan Al-Ruwaili Fahad Mobeirek Sarah Alajaji Waad alqahtani Abdulrahman Areej Alquraini Alosleb Special Thanks to Aleen Alkulyah for the Design! [email protected]