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Classification of lipids  Dietary fat composition ❑ >More than 95% : TG ❑ Cholesterol, ❑ Cholesteryl esters, ❑ Phospholipids, and ❑ Unesterified fatty acids. Dietary sources of lipids Triacylglycerol Phospholipid Phospholipid Sphingomyelin Phosphatidylinositol Cholesterol ...

Classification of lipids  Dietary fat composition ❑ >More than 95% : TG ❑ Cholesterol, ❑ Cholesteryl esters, ❑ Phospholipids, and ❑ Unesterified fatty acids. Dietary sources of lipids Triacylglycerol Phospholipid Phospholipid Sphingomyelin Phosphatidylinositol Cholesterol  Ether of cholesterol Cholesteryl esters function as a transport form of cholesterol in blood plasma and cells in lipid droplets. They serve as storage containers to buffer excess cholesterol. They also serve as pool for cholesterol, for example for hormone synthesis in the adrenal glands, but also for free fatty acids. Functions of lipids Storage form of energy – Concentrated storage – 9.24kcal/g Bio membrane – Structural components – Phospholipids – Glycolipids  Metabolic regulator – Steroid hormones – Prostaglandins Surfactant – Diphosphatidylcholin e (Lecithin) Detergent, emulsifier  Electric insulator of neuron Insulator from external temperature Shape and contour to the body  Cushioning to internal organs Fat soluble vitamins Taste and palatability Digestion of lipids  Digestion in Mouth Lingual lipase 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. Triglyceride degradation  Digestion in Stomach Gastric Lipase Optimum p H 5.4 (4-7) Acid stable Gastrin→ Chief cells Requires the presence of Ca2+ Short and medium chain fatty acid (30%)  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 the milk fat globule and initiate the digestive process.  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: the breaking up of fat globules into much smaller emulsion droplets. Emulsification of fats by bile salts  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  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  GI hormones Secretin- ↑ secretion of electrolytes and HCO3- rich fluid components of pancreatic juice Cholecystokinin Simulates the secretion of the pancreatic enzymes Contraction of the gall bladder Dilatation of sphincter of Oddi Hepatocrinin Released by the intestinal mucosa stimulates more bile formation (poor in bile acid)  Contents of Pancreatic Juice ❑ Pancreatic Lipase - Triglycerides ❑ Phospholipases - Phospholipids ❑ Cholesterol esterase - Cholesteryl esters Hydrolysis of triacylglycerol in intestine. 1-st stage Lipase О СН2 – О – С – С17Н35 СН2 – ОН О +2 Н2О О СН – О – С – С15Н31 СН – О – С – С15Н31 О СН2 – О – С – С17Н29 СН2 – ОН Lipase С17Н35СООН + С17Н29СООН  Isomerisation of 2- monoacyl glycerol, 2-nd stage СН2 – ОН СН2 – ОН О СН – О – С – С15Н31 СН – ОН О СН2 – ОН СН2 – О – С – С15Н31  Hydrolysis of 3-monoacylglycerol. 3-rd stage. СН2 – ОН СН2– ОН + Н2О СН – ОН СН – ОН О СН2 – О – С – С15Н31 СН2 – ОН С15Н31СООН Lipase Approximately 3/4 of TAG after hydrolysis remains in the form of 2-MAG and only 1/4 of TAG is completely hydrolyzed. Hydrolysis of phospholipids in intestine Emulsification and Digestion of TG  Cholesteryl ester degradation Dietary cholesterol mainly free (non-esterified) form 10-15% is in esterified form Hydrolase : activity ↑ by bile salts  Absorption of Lipids 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 form mixed micelles with bile salts  Micelles Spherical Clusters of amphipathic lipids hydrophobic groups on theinside 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 The micelles are absorbed by the enterocytes of the small intestine through endocytosis. In enterocytes takes place resynthesis of TAG from monoglycerides and FA of micelles. Resynthesized TAG are incorporated into chylomicrons.  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 Synthesis of chylomicrons in intestine Intestinum Chylomicrons Complex Fatty acids, Bile acids Lymphatic vessel glycerol, choline Blood  Chylomicron is complex of lipids and special proteins - apoproteins apoproteins Hydrophylic surface Phospholipids Hydrophobic nucleus: Ethers of cholesterol triacylglycerols Cholesterol The major apolipoprotein associated with chylomicrons as they leave the intestinal cells is B-48.  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 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. Metabolism of chylomicrons  Alimentary hyperlipemia 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.  Interaction of chylomicron with a cell receptor apoprotein Ш ШШ Cell Ш membrane Ш Ш Ш Ш ШШ Ш Ш receptor Ш Chylomicron filled with triglycerides Interaction of chylomicron with a cell receptor Ш ШШ Cytosol Ш Ш Ш Ш Ш ШШ Ш Ш receptor Ш Penetration of the chylomicron into the cell Ш ШШ Ш Ш Ш Ш Ш ШШ Ш Ш Ш Hydrolysis of receptor Destruction of the chylomicron inside the cell Ш Ш ШШ Ш Ш Ш Ш ШШ Ш Ш Ш  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 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.