1. LIPIDS Biochemistry Department

2. Lipid Digestion & absoption

3. © I L O Intended Learning Outcomes By the end of this lecture, the student should be capable of: 1.Recognizing the definition, types, & functions of dietary lipids. 2.Identifying enzymes and requirements needed for digestion and absorption of lipids. 3.Finding the role of different GIT organs in processing 4.summarizing the 5phases of digestion and absorption. 5.explaining modes of degradation of lipids 6.Describe the hormonal control of lipid digestion. 7.Describing some abnormalities in lipid metabolism ( digestion and absorption)

4. Preparatory L1Questions What is Lipid? What are the types of dietary lipids known for you? What is the general name of enzymes digesting lipid? How and where does digestion and absorption of lipids occur? Can digestion of lipid be regulated? If yes, then How? Do you know any abnormalities concerning lipid digestion or /and absorption?

5. What Are Lipids ?

6. Lipids are heterogeneous group of water-insoluble (hydrophobic) organic molecules. They are highly soluble in non-polar (organic) solvents as benzene, chloroform and ether

7. Complex Lipids as: phospholipids Glycolipids Lipoproteins Fatty acids & Triacylglycerol Cholesterol & Steroids Phosphate CHO Protein

8. Fatty acids & Triacylglycerol

9. Cholesterol & Steroids

10. Complex Lipids as:

11. Major energy source. Structural function in biomembranes (C+PL). Provide essential FA, fat-soluble vitamins, prostanoids, leukotrienes and steroid hormones. Insulators: thermal (Adipose T) & electrical (myelinated nerves). Forms 2 nd messengers(PI). Alveolar-surfactant(dipalmitoyl lecithin) Defects in lipid metabolism lead to major clinical problems. What are their functions?

12. Body Lipids are generally compartmentalized (in membrane-associated lipids or droplets of TAG in adipocytes), or transported in plasma with protein (lipoproteins, or on albumin). CE** TG PL* FFA- Cholesterol Albumin PL* TG Lipoprotein Adipose tissue Membranes Body Lipids (TAG) = 16 %. (CE) = 36 %. (C) = 14 %. (PL) = 30 %. (FFA’s) = 4 %

13. The rest are :cholesterol, cholesteryl esters, phospholipids, and unesterified (“free”) fatty acids. Dietary Lipids The average daily intake (81g) by U.S. adults, of which 90% is (TAG) 1gm The energy yield from 1gm lipid is 9Kcal while that of 1gm carbohydrate is 4 kcal

14. Do Not Forget enzymes of digestion in stomach and intestine are: Lipases That Require *Ca ions (for enzyme action) *Bile( for emulsification) *Colipase (for exposure of active sites of the enzymes)

15. Emulsification increases the surface area of the hydrophobic lipid droplets so that the digestive enzymes, can act effectively.

16. A protein, Colipase, secreted as a zymogen (procolipase) by the pancreas and is activated in the intestine by trypsin; it binds the lipases to exposes their active sites. Colipase deficiency (with normal lipase) is accompanied by significant lipid malabsorption.

17. H 2-Monoacylglycerol fatty acid

18. Cholesterol +Fatty acid

19. H H Glycerophosphocholine+FFA Lysophospholipid+FFA Phospholipase A2 Lysophospholipase OH

20. Degradation of lipids by pancreatic enzymes Cholesterol+FFA C FA CE G P Choline P PLA2 LysopL+FFA Lyso-PLA P Choline Glycerophosphocholine+FFA PL FA

21. 5 Phases of Digestion & absorption are as follows:

22. I-Digestion (hydrolysis) (in stomach & intestine) -Acid stable lipases -Emulsification -Pancreatic enzymes II- Solubilization in Micelles III- Uptake by enterocytes (Absorption) IV- Incorporation in Chylomicron. V-Exocytosis of Chylomicron

23. I-Digestion (hydrolysis) (in stomach & intestine) -Acid stable lipases -Emulsification -Pancreatic enzymes

24. A. Processing of dietary lipid in the stomach The digestion of lipids begins in the stomach, by an acid-stable lipases (lingual and gastric) Acid –stable Lipases ?

25. Acid–stable Lipases degrading TAG with short to medium –FA (milk). Optimum pH 4 - 6. Important in neonates Pancreatic insufficiency e.g cystic fibrosis (Due to long retention in stomach(2-4h) 30% of TAG could be hydrolyzed)

26. B. Emulsification of dietary lipid in the small intestine (duodenum) peristalsis Bile peristalsis Emulsification Bile salts, made in the liver and stored in the gallbladder.

27. The dietary TAG, CE, and PL are degraded by pancreatic enzymes, whose secretion is hormonally controlled. Pancreatic Enzymes C. Degradation of dietary lipids by pancreatic enzymes Lipases

28. The esterase, pancreatic lipase, removes FA at C1 & C3 giving 2- MAG + FFAs. TAG degradation: bile salts+ Ca++

29. Because an isomerase enzyme will be needed (the process needs time) Q Why TAG Is not completely Hydrolyzed?

30. Most cholesterol is free, 10–15% is CE. Pancreatic cholesteryl ester hydrolase (esterase) it gives free fatty acids +Cholesterol. Cholesteryl ester degradation: bile salts+ Ca ++

31. PLA2 removes (C2FA) giving lysophospholipid. (C1FA) is then removed by lysophospholipase, giving a glycerylphosphoryl-choline. The rest may be excreted, degraded, or absorbed. Phospholipid degradation: bile salts+ Ca++

32. What are the end products of hydrolysis (absorbed particles)? Bile---Absorbed (enterohepatic circulation) 2-MAG FFA Cholesterol PL Lyso PL NB Fat soluble vitamins

33. - Cholecystokinin(CCK) (duodenum) -Secretin (intestinal cells) is released also due to the low pH of the chyme entering the intestine. It causes the release of rich bicarbonate solution to neutralize the pH and to prepare for the action of pancreatic digestive enzymes. Hormonal Control of lipid digestion BY 2 small peptide hormones:

34. Micelles are disk shaped clusters of amphipathic lipids= [inside hydrophobic & hydrophilic outside] Therefore Are soluble in aqueous environment of the intestine. II. Solubilization in micelles Short-& medium-chain fatty acids do not require micelles formation. FA C Bile salts 2-MAG

35. III-uptake by enterocytes & Resynthesis (Absorption) Endoplasmic reticulum In Endoplasmic reticulum

36. IV- Incorporation in chylomicron (Secretion) TAGs and CE are very hydrophobic. Therefore, chylomicrons are formed Apo-48 stabilizes & increases the solubility, preventing coalescing. Hydrophobic Hydrophillic 6% 2% 90%

37. How are dietary lipids reach blood? Chylomicrons (ER)  migrates to golgi apparatus to be exo-cytosed into intercellular space.  enter lymph (large)  thoracic duct  blood CM are released by exocytosis from enterocytes into lacteals of lymphatic system to the thoracic duct, and then finally to the blood causing turbidity (chyle). This is known: Postalimentary hyperlipemia V- Exocytosis of chylomicron

38. NB.Short to medium FA are not reesterified to 2-MAG. They are released into the portal circulation directly, where they are carried by serum albumin to the liver

39. other tissues : heart, lung, kidney, and liver etc. Use of dietary lipids by the tissues The degradation of TAG of chylomicron is done by the LPL of capillary endothelium of extra-hepatic tissues TG lipoprotein lipase is synthesized primarily by adipocytes and muscle cells. free fatty acids and glycerol

40. Fate of glycerol: Glycerokinase Glycerol Glycerol-3P ATPADP Mg By the LIVER glycolysis gluconeogenesis PL

41. FFAs may enter directly adjacent muscle cells or adipocytes. Or alternatively, may be transported in the blood by albumin until taken up by cells. Fate of free fatty acids: FA Oxidized in most tissues to give energy Reestrified in adipocytes to be stored as TAG

42. Fate of remaining chylomicron components: CE,PL, Apoprot.,Fat sol. Vit, some TAG Chylomicron remnants bind to receptors on the liver and endocytosed.

43. Pathological Conditions affecting Fat Digestion and Absorption This occur due to: 1-Deficiency of Pancreatic lipases or co-lipase e.g. pancreatitis…etc. 2-Deficiency of Bile salts (whitish clay stool) e.g. Obstruction of bile duct, cholycystitis and hepatitis 3-Any disease affecting intestinal absorption. Fatty diarrhea, fatty stool, milky stool or Steatorrhea.

45. Familial lipoprotein lipase deficiency: is a rare disorder resulting from deficiency of the enzyme or its coenzyme apo C-II. The result is chylomicronemia (Type I hyperlipoproteinemia)

46. -This condition occurs If removal of chylomicron remnants by the liver is defective, as they accumulate in the plasma. Type III hyperlipoproteinemia (also called familial dysbetalipoproteinemia)

47. Choose the ONE correct answer. Which one of the following statements about the absorption of lipids from the intestine is correct? A.Dietary triacylglycerol is partially hydrolyzed and absorbed as free fatty acids and monoacylglycerol. B. Dietary triacylglycerol must be completely hydrolyzed to free fatty acids and glycerol before absorption. C. Release of fatty acids from triacylglycerol in the intestine is inhibited by bile salts. D. Fatty acids that contain ten carbons or less are absorbed and enter the circulation primarily via the lymphatic system. E. Formation of chylomicrons is independent of protein synthesis in the intestinal mucosa.

49. Lipases require *Calcium ions (for enzyme action),---------( for emulsification) and------- (for exposure of active sites of the enzyme). Hydrolysis by: *Pancreatic lipase to Diacylglycerol  -------+----- *Pancreatic lipase to Cholesterol ester  ------+------- *Phospholipase A2 to phospholipid  --------+-------- *The 2 regulatoy hormones of digestion are--- +---- *Lipid solubilization in intestinal lumen for proper absorption needs ------formation,while in circulation formation of --------is needed.

50. Lipases require *Calcium ions (for enzyme action),Bile( for emulsification) and Co-lipase(for exposure of active sites of the enzyme). Hydrolysis by: *Pancreatic lipase to Diacylglycerol  2-MAG+ FFA *Pancreatic lipase to Cholesterol ester  C+FFA *Phospholipase A2 to phospholipid  lysophospholipids +FFA *The 2 regulatoy hormones of digestion are Cholecystokinin+ Secretin *Lipid solubilization in intestinal lumen for proper absorption needs Micelles formation,while in circulation formation of Lipoprotein is needed.