Lipid Metabolism

1. Lipid Metabolism Digestion & absorption

2. Introduction • Fat is a good source of energy as 1 gm supplies 9.1 calories, which is over double that supplied by carbohydrates or protein. • Dietary lipidsare ingested in form of triglycerides,phosholipids,cholesterol and free fatty acids. • A minimal amount of fat is essential in our food to provide an adequate supply of the essential fatty acids.

3. Lipids are esters of fatty acids with various alcohols: R-COOH + R-OH RCOOR + H2O Fatty acid + Alcohol Ester + Water • Fatsareesters of fatty acids with glycerol called triglycerides because they are tri-esters of glycerol

4. Fatty acids These are carboxylic acids their general formula R- COOH. fatty acids are classified into • saturated • unsaturated fatty acids according to absence or presence of double bonds.

5. 1- Saturated fatty acids • Saturated chain fatty acids are based on acetic acid CH3-COOH. • no double bonds CH3 - COOH is acetic acid, CH3 – CH2 – COOHis propionic acid CH3 – CH2 – CH2 – COOH butyric acid and so on.

6. 2- Unsaturated fatty acids They have one or more double bonds.

7. Biological Importance Of Lipids: 1- Energy production, dietary lipids supply the body with about 25% of calories needed every day. 2- They provide the body with • Essential fatty acid • Fat soluble vitamins • Phosphours in the form of phospholipids

8. Fats under the skin are used as insulater protecting the body against external temp. • Combinations of fat and protein (lipoproteins) are important cellular constituents and serve for the transport of lipids in the blood. • Cholestrol is used for synthesis of adrenal cortical hormones, vitamin D3 and bile acids.

9. Digestion of lipids 1- Digestion of triglycerides: • Ingested triglycerides first are emulsified and then undergo enzymatic hydrolysis by lipase enzymes. 1- Emulsification: • Breakdown of large fat globule into small ones • done in the mouth by chewing. • in the stomach by peristaltic contractions. • in intestine by peristaltic movement, bile salts.

11. 2- Digestive fat enzymes: • Are lingual lipase, gastric lipase, pancreatic lipaseandintestinal lipase. • The most active is pancreatic lipase. 1-Lingual lipase: Is secreted by the dorsal surface of the tongue (Ebner's glands), but this enzyme is not of much significance in humans as compared with rat or mouse.

12. 2-Gastric lipase (pH 3-6): In the stomach some digestion occurs by gastric lipase hydrolyzing triglycerides containing short, medium and unsaturated long chain fatty acids to form FFA and 1,2 diglycerides

14. 3-Pancreatic lipase: • Bile salts assist emulsification by lowering surface tension exposing large area of triglycerides pancreatic lipase will dissolve fatty acids.

15. Pancreatic lipase acts on finely emulsified lipid droplets in presence of 1- bile salts. 2- colipase (a protein present in pancreatic secretion). 3- phospholipase A2 (Ca++ is necessary for phospholipase A2 activity).

16. Pancreatic lipase hydrolyses the primary ester bond with the production of 2FFA + β-monoglyceride. • Hydrolysis of monoglyceride requires transfer of the FA from beta to alpha carbons of glycerol by specific isomerase enzyme. this process is very slow. So the major digestion products of TGareβ-monoglyceride and FA.

18. 4-Intestinal lipase: Act within intestinal mucosal cells where it may hydrolyse primary monoglyceride glycerol and FFA.

19. 2-Digestion of phospholipids: • Glycerophospholipids are hydrolyzed by pancreatic enzyme phospholipase A2 which remove FA in position 2 to form lysophospholipids.

20. Intestinal phospholipase may complete the hydrolysis of lysophospholipids glycerol + FA + phosphoric acid

21. 3-Digestion of cholesterol esters: Cholesterol ester are hydrolyzed by cholesterol ester hydrolase (cholesterol esterase) into FA and free cholesterol

22. Absorptionof lipids • The end products of lipid digestion are: FA – glycerol - monoglyceride - cholesterol and lysophospholipid. 1- Short(less than 10 carbon atoms) and medium chain fatty acids (10-12C) together with free glycerol are water soluble • absorbed to the intestinal cell by diffusion and passes directly to the liver through the portal circulating.

23. 2- monoacylglycerol +long chain fatty acids + cholesterol and lysophosphoatide are absorbed through the plasma membrane of the intestinal cells (jejunum and ileum) together withbile salts forming soluble complexes with them(Micelles).

25. Inside the intestinal cells: • bile salts are separated and carried out to the liver via the portal circulation and then secreted with the bile in the intestine. This known as enterohepatic circulation of bile salts.

26. Inside the intestinal cells: • long chain fatty acids are activated by thiokinase enzyme(acyl COA synthetase) forming acyl COA.

27. AcylCoA esterifies 2-monoacylglycerol at 1 and 3 positions T.G.

28. T.G are formed also from free glycerol in intestinal cells from dihydroxyacetone phosphate (from glycolysis). Activated by glycerokinase enzyme

29. Resynthesis of phospholipids & cholesterol esters by combination of cholesterol and lysophospholipids absorbed with acyl-CoA. • The triglycerides, phospholipids & cholesterol ester and cholesterol bind with a protein (apolipoprotein B48) to formchylomicrons which enter lacteals and pass with lymphatic drainage to the thoracic duct to reach systemic circulation.

31. Fate of absorbed lipid • Immediately after absorption of lipids there is turbidity of plasma due to the circulating chylomicrons (appear in plasma 2 hours after meals). • This turbidity is soon cleared by lipoprotein lipase enzyme (clearing factor). • This enzyme hydrolyses triglycerides of chylomicrons to glycerol and FFA. • Glycerol is transported to liver to be metabolized as carbohydrate.

32. Free fatty acids are carried by plasma albumin to adipose tissues liver and other tissues for metabolism. • MOST dietary fat transported to adipose for storage