1Enzymes for lipid digestionEnzymes for lipid digestionLipid digestion: mouth Salivary lipaseSubstrate: triglyceridesSubstrate: triglycerides End products: diglyceride + 1 fatty acid Minor importance in young animalsDiglycerideFFAGlycerol3 FATriglyceride(DG cannot be absorbed: too big!) Lipid digestion: stomach Gastric lipase is secreted- minor importance (TG to DG + FA) Little digestion occurs (less than 30%)DiglycerideFFAGlycerol3 FATriglyceride(DG cannot be absorbed: too big!)2Lipid digestion: pancreas Pancreatic lipase Substrate: triglycerides, (DG) End products: monoglyceride + 2 FA Co-lipaseMonoglyceride (sn-2)FFAglycerol3 FAtriglyceride(MG can be absorbed) Lipid digestion: pancreas Lecithinase Substrate: lecithin Phosphotidyl-choline (i.e., phospholipid) Found in egg yolk, beef, milk, soybeans End products: lysolecithin, free FA2FALecithin(phophatidylcholine)lysolecithinFFALipid digestion: SI Intestinal lipase Substrate: triglycerides, (DG, MG)gy ,( , ) End products: glycerol + 3 FA Lecithinase Substrate: lecithin End products: lysolecithin, free FAGlycerolFFAglycerol3 FAtriglyceride3Lipolytic enzymes Salivary lipase (mouth) Gastric lipase (stomach) Pancreatic lipase (pancreas) Intestinal lipase (small intestine) Lecithinase (pancreas, small intestine)Salivary lipasePancreatic lipase, lecithinaseIntestinal lipase, lecithinaseGastric lipaseDigestion of lipids4Digestion of lipids Major site of lipid digestion is upper small it tiintestine. Lipids are discharged slowly from the stomach (low pH) and mixed with bile, pancreatic, and intestinal secretions. Bile causes emulsification.Digestion of lipidsEmulsification: The process of dispersing one liquid in a second immiscible (unmixable) liquidEmulsion: A mixture of two or more immiscible liquidsEmulsifier (Emulsifying agents):Soaps, detergents, … bile, lecithin, etc.Digestion of lipids Emulsification is to make fat soluble iit(l fin an aqueous environment(lumen of GIT). To enable digestion To facilitate absorption5Digestion of lipids Emulsification of dietary fat occurring ithl f llittiin the lumen of upper small intestine rearranges fats by their relative ‘hydrophobicity’ Strong hydrophobic: TG, DG, cholesterol ester Weak hydrophobic: MG, FA, cholesterol, bile acid, phospholipidLipid emulsification: Emulsion formationSurface coat:rich in cholesterolCore: rich in TG, DG, and CE(strong hydrophobic)rich in cholesterol, phospholipid, MGfatty acid, bile acid(relatively hydrophilic or weak hydrophobic)TG: triglycerideCE: cholesterol esterLipid digestion by lipolytic enzymesSalivary lipasePLPLDietary fatMouthEsophagus & stomachSmall intestineEmulsionPLPL6Lipid digestion by lipolytic enzymesPLEmulsionPLCholesterolCholesterolFatty acidFatty acidKey processTriglycerides: Emulsion stabilized by bile salts and other surface active compoundsother surface active compoundsPancreatic lipase (w/ intestinal lipase)Unhydrolyzed triglycerides back to core of emulsionDiglycerides Monoglycerides form mixed micelles (or bimolecularFatty acids discs) stabilized by bile saltsGlycerolKey process1. Hydrolysis of TG in the core of emulsion by pancreatic lipase2. TG (core) → MG + 2 fatty acids (go to surface)3. Reduction of core and increase of ‘surface coat’4. Protrusion of surface coats composed of fatty acids, phospholipids, MG, glycerol, cholesterol, bile5. Protruded surface coats will be detached from emulsion becoming ‘mixed micelles’7Key process1. Change in physical states of lipids caused by TG hydrolysis2. Importance of conversion of TG-rich emulsion into mixed micelles1. Mixed micelles are sufficiently small enough to allow the entry into the inter-microvilli space of intestinal mucosal cells 2. Plasma membrane of microvilli of intestinal mucosal cells allows the efficient molecular penetration of FFA and MG but not of TG and DGPancreatic lipasePancreatic lipaseTG emulsionMixed micelleMicrovilli on an enterocytePancreatic lipase Substrates must be in the form of liemulsions Pancreatic lipase must be adsorbed by the interface: colipase is required for this step8Pancreatic lipase Pancreatic lipase hydrolyzes specifically th t f i l h lthe esters of primary alcohol Hydrolysis rate: TG > DG Pancreatic lipase cannot hydrolyze monoglyceride at sn-2 positionPancreatic lipaseLid domain2 small loopsCatalytic triad (Ser-His-Asp )Pancreatic lipase Lid domainp(5 AA)Pancreatic lipaseWaterlipid interfaceTG-EmulsionColipaseLid is openedWater-lipid interfaceCatalytic triad is not accessible9Bile acidsCholic acid (hydrophobic)AmphipathicGlycine or taurine(hydrophilic)Role of bile acids1. Emulsification of dietary fat2. Structure mixed micellesMixed micelle formation upon TG hydrolysis of emulsion particles3. Uptake of FA and MG from proximal jejunumAbsorption of lipid10Absorption of lipids1. Uptake of monoglycerides, fatty acids, and glycerol by enterocytes and moved to sER2. Re-synthesis of triglycerides (TG) in sER of enterocytes3. Form a lipid particle, chylomicrons (CMs), in sER (**chylomicron is a lipoprotein)4. Intracellular transport of chylomicrons5. Release of chylomicrons from enterocytes6. Chylomicrons into lymphatic vesselsAbsorption of lipidsTG-rich emulsionDietary fat (TG)Lumen of SIFA in mixed micelleFAby molecular penetrationTG re-synthesis in ERTG-rich chylomicronsTo blood circulationEnterocytesERAbsorption of lipids11LiverEmulsionAdipocyteTransport of lipid: LipoproteinsLipoproteinsTransport of lipids Re-synthesized TG (in sER) and cholesterols are transported as a part oflipoproteinsin blood vesselsof lipoproteinsin blood vessels From small intestine: Chylomicron cf. from liver Low density lipoprotein (LDL) Very low density lipoprotein (VLDL) cf. from non-hepatic tissues (…muscle) High density lipoprotein (HDL)12Transport of lipids:Lipoprotein composition80%90%100%0%10%20%30%40%50%60%70%80%CMs VLDL LDL HDLTriglycerideCholesterolPhospholipidProteinSize:CMs>VLDL>LDL>HDL Chylomicron (CM): Very low density lipoprotein (VLDL):13 Low density lipoprotein (LDL): High density lipoprotein (HDL): Cholesterol from non-hepatic tussues to liver for xtinexcretionTransport of lipids:Function of lipoproteins Small intestine to LiverChylomicron (TG)Chylomicron (TG) Liver to Non-hepatic tissues VLDL (TG) LDL (Cholesterol) Non-hepatic tissues to Liver HDL
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