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Hydrogenation adding H s to an unsaturated fat to make it solid at room temperature HUN3224 Fatty acid structure Metabolism of Lipids o CH3 CH2 CH2 CH2 COOH o Methyl end carboxyl end o 4 24 carbons long o Most are even numbered carbon chains o Saturated o Monounsaturated 1 double bond i e olive oil canola oil o Polyunsaturated Essential fatty acids o Double bonds are always 3 carbons apart o Methyl end omega or n end o Carboxyl end alpha or delta end How to name a fatty acid o Count the number of carbons o Count the number of double bonds o Name according to omega or alpha Ex 18 Ex 2 i e 18 2n6 Essential fatty acids o Linoleic acid 18 2n6 omega 6 o linolenic 18 3n3 omega 3 Eicosanoids o responsible for modulation of platelet aggregation immune system smooth muscle contraction nervous system o Families prostacyclins 18 number of carbons in chain 2 number of double bonds 6 site of first double bond counting from the omega methyl end HUN3224 function vasodilator platelet anti aggregation site of synthesis vascular endothelium function vasoconstrictor platelet aggregation site of synthesis platelets Function vascular contraction inflammation site of synthesis leukocytes thrombaxanes leukotrienes prostaglandins functions smooth muscle contraction and relaxation site of synthesis endothelium of a variety of cells o Eicosanoids synthesized from Arachidonate acid 20 4n6 Eicosatrienoic acid 20 3n6 Eicosapentanoic acid 20 5n3 Lipids o Triglycerides 3 fatty acids Glycerol backbone o Phospholipids Glycerol backbone 1 or more fatty acids 1 phosphate o Glycolipids Lipid and CHO o Sterols Lipid digestion Steroid nucleus Cholesterol Bile acid Steroidal sex hormones Adrenocorticoid hormones Vitamin D synthesis o Lingual salivary lipase o Biliary Emulsification Secreted at base of tongue Stable at low pH Efficient in digestion of milk fat infants Dispersion of fat in an aqueous solution Allows for lipase action Bile salt emulsification agent HUN3224 o Lipolysis 3 main enzymes Pancreatic lipase o Breaks down glycerol backbones and 3 fatty acids Cholesterol esterase Lecithinase o Breakdown to cholesterol and fatty acid o Breakdown to lysolecithin and fatty acid o Lipid Absorption Micelle formation Fatty elements and fat soluble vitamins surrounded by bile salts Passive diffusion of fatty elements and vitamins at distal duodenum and jejunum Bile salts absorbed in ileum and retuned to liver via EHC enterohepatic circulation o Inside the enterocyte Long chain fatty acids 12 carbons and other fatty acid components with coenzyme A Reformation of triglycerides cholesterol esters and phospholipids Triglycerides and fatty components and proteins chylomicron Short chain fatty acids attach to albumin and travel through portal blood to tissues Lipoproteins protein complexes which carry lipid products i e cholesterol in the blood lymph to various tissues o Chylomicron formed in enterocytes from exogenous lipids released into lymph composition 80 triglycerides 15 cholesterol and phospholipids Apoproteins A B C E Size 90 100 nm formed in liver and released into the blood composition 50 triglycerides 20 phospholipids 20 cholesterol Apoproteins B C Size 30 90 nm o VLDL o LDL formed from IDL after triglyceride hydrolysis function delivers cholesterol to non hepatic tissues HUN3224 uptake via receptor mediated endocytosis composition 50 cholesterol 9 triglycerides 23 phospholipids Apoprotein B100 20 cholesterol 3 triglycerides 30 phospholipids Apoproteins A C D E o HDL formed in liver and intestine function removal of cholesterol from non hepatic tissues can also pick up cholesterol from cell membranes composition o Lecithin cholesterol acyl transferase LCAT allows HDL to pick up cholesterol from cell membranes or from other lipoproteins ApoA1 binds to LCAT receptors cholesterol cholesterol ester phospholipid lysolecithin lysolecithin binds to albumin HDL transports cholesterol ester back to liver o By picking up cholesterol from inside the cell receptor mediated endocytosis can increase lowering amount of LDL in the bloodstream o Almost all tissues with nucleated cells can synthesize cholesterol in cytosol and ER Receptor mediated endocytosis o 1 Receptor located in clatharin coated pits o 2 Receptor is specific for proteins ApoB100 receptor for LDL o 3 LDL and receptor bind o 4 LDL and receptor complex are internalized forms vesicle o 5 Vesicle fuses with lysosome o 6 pH changes o 7 ApoB degraded into amino acids o 8 Cholesterol released into cells o 9 Receptor returns to surface Regulations of cholesterol synthesis o HMG CoA reductase activity rate limiting enzyme reduced by cholesterol HUN3224 glucagon glucocorticoid hormones fasting all need acetyl CoA to make energy therefore it cannot be used to make cholesterol o dietary cholesterol also affects rate of cholesterol synthesis if we eat enough we won t make it recommended cholesterol intake 300 mg d average intake 600 mg d o When we turn off receptors LDL remains in the bloodstream Transportation of cholesterol o HDL transports cholesterol from tissues to liver o LDL transports cholesterol from liver to tissues o Functions of cholesterol Maintains fluidity of cell membranes Steroid hormones Vitamin D synthesis Bile production Bile composition o 82 water o 12 bile salts o 4 phospholipids o Bile pigments biliverdin and bilirubin Bile synthesis o Hepatocytes CCK Secretin Gastrin Stimulates bile release from gallbladder o Stored in gallbladder o Travels through Sphincter of Oddi into duodenum via bile duct Function of bile lipid emulsification essential for fat digestion Fatty acid synthesis o Glucose primary substrate o Membrane permeability place o Fatty acid synthase complex Components Acetyl CoA and oxaloacetate cannot cross the mitochondrial membrane But pyruvate and citrate can Needs to cross over from mitochondria to cytosol where synthesis takes HUN3224 Thioesterase Acyl carrier protein Ketoacyl reductase Enoyl reductase Hydratase Transcyclase 2 Ketoacyl synthase Active complex Dimer of 2 identical polypeptide monomers Monomers connected by 2 disulfide bonds 14 subunits Desaturation addition of double bonds Essential fatty acids o Lack enzymes 12 and 15 desaturase which add bonds past the 9 position 18 2 9 12 linoleic acid 18 3 9 12 15 linolenic acid De novo fatty acids are 16 carbons long Elongate then desaturate First double bond will heat 9 These fats are essential because we do not have the enzymes to forms the double bonds at these locations in the


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FSU HUN 3224 - Metabolism of Lipids

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