Lecture_1-2_Lipids.pptxrhshsehtsrhrtshrhrh
- 3. Dietary fatcomposition >More than 95% : TG Cholesterol, Cholesteryl esters, Phospholipids, and Unesterified fatty acids.
- 5. Classification of lipids Simple triacylgly- cerols (fats) Complex phospholipids Glycolipids Steroids glycero- cerebrosides ganglyosides phospholipids sphingolipids Sulfatides
- 6. О СН2 – О – С – С17Н35 О СН – О– С – С15Н31 О СН2 – О – С – С17Н31 Triacylglycerol
- 7. Structure of phospholipid Hydrophylic site hydrophobic site (residues of two fatty acids) (CН3) О N+ СН2-О-С СН3 СН2 О СН2 СН -О-С СН3 О -О-Р-О СН2 О
- 9. Sphingomyelin СН2- ОН Р Choline СН – NН2 fatty acid СН – ОН СН СН СН3
- 10. ОН ОН О СН2 – О – С СН3 НО ОН О ОН О СН – О –С СН3 – О–Р О СН2 О Phosphatidylinositol
- 13. Functions • Storage form of energy – Concentrated storage – 9.24kcal/g • Bio membrane – Structural components – Phospholipids – Glycolipids
- 14. • Metabolic regulator – Steroid hormones – Prostaglandins • Surfactant – Diphosphatidylcholine (Lecithin) • Detergent, emulsifier
- 15. • Electric insulator of neuron • Insulator from external temperature • Shape and contour to the body
- 16. • Cushioning to internal organs • Fat soluble vitamins • Taste and palatability
- 17. Digestion in Mouth TG 1,2 DAG +FFA Lingual lipase: Secreted by dorsal surface of tongue Active at low pH (pH 2.0 – 7-5) optimum pH 4.0-4.5 Ideal substrate-Short chain TGS Enzymatic action continues in stomach Short chain fatty acids: absorbed directly from the stomach wall Enter the portal vein. Lingual lipase
- 19. Digestion inStomach Gastric Lipase • Optimum p H 5.4 (4-7) • Acid stable • Gastrin→ Chief cells • Requires the presence of Ca++ • Short and medium chain fatty acid (30%)
- 20. Significance of Lingual & Gastric Lipases • Neonates These enzymes are essential for the digestion of milk fat in the newborn because, contrary to other digestive lipases (pancreatic or milk digestive lipase), lingual and gastric lipases can penetrate into the milk fat globule and initiate the digestive process.
- 21. Emulsification anddigestion Lipids • hydrophobic • poorly soluble in the aqueous environment • Lipase, : water soluble • can only work at the surface of fat globules. Digestion is greatly aided by Emulsification : breaking up of fat globules into much smaller emulsion droplets.
- 22. Bile salts Emulsification of fats by bile salt
- 23. Bile Salts • Synthesized in the liver • Stored in the gallbladder • Derivatives of cholesterol • sterol ring + side chain + glycine / Taurine • Na & K salts of Glycocholic & Taurocholic acid • Entero-hepatic circulation
- 24. Digestion in small intestine • Major site of fat digestion • Effective → Pancreatic lipase and bile salts. • Bile salts → effective emulsifying agents • Secretion of pancreatic juice is stimulated by • Gastric acid /Protein-rich content in duodenum • Production of Secretin/Cholecystokinin/Pancreozymin
- 25. GI hormones Secretin- ↑ secretion of electrolytes and HCO3 - rich fluid components of pancreatic juice Pancreozymin stimulates the secretion of the pancreatic enzymes Cholecystokinin Contraction of the gall bladder Dilatation of sphincter of Oddi Hepatocrinin- Released by the intestinal mucosa stimulates more bile formation (poor in bile acid)
- 26. Contents of Pancreatic Juice Pancreatic Lipase - triglycerides Phospholipases - Phospholipids Cholesterol esterase - Cholesteryl esters
- 27. Hydrolysis of triacylglycerol in intestine. 1-st stage О СН2 – О – С – С17Н35 О СН – О – С – С15Н31 О СН2 – О – С – С17Н29 Lipase Lipase СН2 – ОН О СН – О – С – С15Н31 СН2 – ОН +2 Н2О С17Н35СООН С17Н29СООН +
- 28. СН2 – ОН О СН – О – С – С15Н31 СН2 – ОН СН2 – ОН СН – ОН О СН2 – О – С – С15Н31 Isomerisation of 2- monoacyl glycerol, 2-nd stage
- 29. СН2 – ОН СН – ОН О СН2 – О – С – С15Н31 Lipase СН2– ОН СН – ОН СН2 – ОН С15Н31СООН + Н2О Hydrolysis of 3-monoacylglycerol. 3-rd stage.
- 30. Hydrolysis of phospholipids in intestine (CН3) О N+ СН2-О С СН3 СН2 О СН2 СН-О С СН3 О -О-Р О СН2 О Phospholipase А1 Phospholipase А2 Phospholipase С Phospholipase D
- 32. Cholesteryl esterdegradation • Dietary cholesterol • mainly free (Non-esterified) form • 10-15% is in esterified form • Hydrolase : activity ↑ by bile salts
- 33. Absorption ofLipids Glycerol, short chain FA & medium chain FA are directly absorbed from the intestinal lumen → portal vein → liver Long-chain fatty acids, free cholesterol and β-acyl glycerol With bile salts form mixed micelles
- 34. Micelles • Spherical • Clusters of amphipathic lipids • hydrophobic groups on the inside • hydrophilic groups on the outside of clusters • Mixed micelles : soluble in the aqueous environment of the intestinal lumen • Approach the brush border membrane of the enterocytes
- 35. Synthesis of chylomicrons in intestine Within the intestinal epithelial cells, the fatty acids and 2-monoacylglycerols are condensed by enzymatic reactions in the smooth endoplasmic reticulum (ER) to form triacylglycerols. The fatty acids are activated to fatty acyl-coenzyme A (fatty acyl-CoA) by the same process used for the activation of fatty acids before. A fatty acyl-CoA then reacts with 2- monoacylglycerol to form diacylglycerol, which reacts with another fatty acyl-CoA to form triacylglycerol. Intestinal cells package triacylglycerols together with proteins and phospholipids in chylomicrons, which are lipoprotein particles that do not readily coalesce in aqueous solutions
- 36. Complex Bile acids Fatty acids, glycerol, choline Intestinum Chylomicrons Lymphatic vessel Blood Synthesis of chylomicrons in intestine
- 37. Chylomicron is complex of lipids and special proteins - apoproteins apoproteins Hydrophobic nucleus: Ethers of cholesterol triacylglycerols Cholesterol Phospholipids Hydrophylic surface The major apolipoprotein associated with chylomicrons as they leave the intestinal cells is B-48.
- 38. Transport of Dietary Lipids in the Blood By the process of exocytosis, nascent chylomicrons are secreted by the intestinal epithelial cells into the chyle of the lymphatic system and enter the blood through the thoracic duct. Nascent chylomicrons begin to enter the blood within 1 to 2 hours after the start of a meal; as the meal is digested and absorbed, they continue to enter the blood for many hours. Initially, the particles are called nascent (newborn) chylomicrons. As they accept proteins from HDL within the lymph and the blood, they become “mature” chylomicrons. HDL is the lipoprotein particle with the highest concentration of proteins, and lowest concentration of triacylglycerol.
- 39. Alimentary hyperlipemia is observed 1 to 2 hours after a meal containing lipids. The serum obtained after centrifugation of the blood becomes turbid “strawberry-cream blood". The peak of alimentary hyperlipemia occurs 4-6 hours after ingestion of fatty foods. Usually, after 10 - 12 hours the content of chylomicrons in the blood returns to normal values. The presence of chylomicrons in the blood interferes with biochemical studies of the blood serum of patients. Therefore, blood sampling for analysis is performed on an empty stomach, that is, in the morning before eating.
- 40. Transport of lipids in blood
- 41. Interaction of chylomicron with a cell receptor receptor Chylomicron filled with triglycerides Cell membrane apoprotein
- 42. Interaction of chylomicron with a cell receptor Cytosol receptor
- 43. Penetration of the chylomicron into the cell Hydrolysis of receptor
- 44. Destruction of the chylomicron inside the cell
- 45. Lipid Malabsorption (Steatorrhea) • Lipids loss (including fat soluble vitamins A,D E and K) in the feces. • Cause • pancreatic insufficiency • cystic fibrosis • chronic diseases of the pancreas • surgical removal of pancreas • shortened bowel, Celiac diseases, sprue or Crohn’s disease • bile duct obstruction
- 46. Summary of lipid digestion and absorption Chylomicrons deliver absorbed TAG to the body's cells. TAG in chylomicrons and other lipoproteins are hydrolyzed by lipoprotein lipase, an enzyme that is found in capillary endothelial cells. Monoglycerides and fatty acids released from digestion of TAG then diffuse into cells.