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Section VI. Lipid Metabolism

Section VI. Lipid Metabolism. Section VI. Lipid metabolism overview: Major categories of lipids (not very water-soluble) : Fatty acids and triagylclycerol (TG) Glycerophospholipids and sphingolipids Eicosanoids (prostaglandins, thromboxanes) Cholesterol, bile salts, steroid hormones

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Section VI. Lipid Metabolism

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  1. Section VI. Lipid Metabolism • Section VI. Lipid metabolism overview: • Major categories of lipids (not very water-soluble): • Fatty acids and triagylclycerol (TG) • Glycerophospholipids and sphingolipids • Eicosanoids (prostaglandins, thromboxanes) • Cholesterol, bile salts, steroid hormones • Fat-soluble vitamins (A, D, E, K) Triacylglycerol

  2. Overview Fatty acid metabolism • Fatty acid metabolism: (Chapts. 32, 33) • Fatty acids can be dietary or synthesized in liver • Can be oxidized for energy → CO2 and H2O • Can be stored as triacylglycerol in adipose tissue • Can be used to make phospholipids and sphingolipids for membrane components

  3. Overview of cholesterol metabolism • Cholesterol metabolism (chapt. 34): • Is incorporated into membranes for stability • Is a precursor for bile salts (gall bladder secretes) • Is a precursor for steroid hormones

  4. Overview lipoprotein particles in blood • Lipoprotein particles transport lipids in blood: • Triacylglycerol is major dietary lipid: • Digested in intestinal lumen: free FA and 2-mono-acylglycerol are reconverted to TG in intestinal cells • TG are packaged as chylomicrons (apoB) and secreted into blood ; matured with additional proteins • VLDL (very-low-density-lipoproteins) produced in liver from dietary carbohydrates (insulin stimulated) • Lipoprotein lipase (LPL) on cells degrades the lipoproteins; FA into cells • HDL (high-density-lipoproteins) transport excess cholesterol to liver; exchange proteins

  5. Lipid metabolism overview • Triacylglycerol metabolism: • Fed state: • TG digested to 2-MG and FA, into intestinal cells • TG reform (chylomicrons) with protein, into blood • Liver forms VLDL by lipogenesis from sugars • VLDL donates protein to chylomicron, which binds LPL on cells and is cleaved to release FA into muscle, adipose • Fasting state: • Fatty acids, glycerol released from adipose • Glycerol used for gluconeogenesis liver • FA used for ketone bodies, or oxidation (muscles, other)

  6. Chapt. 32 • Ch. 32 Digestion and Transport • of Dietary Lipids • Student Learning Outcomes: • Explain digestion of triacylglycerols (TG) to free fatty acids (FA) and 2-monoacylglycerol(2-MG) • Describe the role of bile salts in this process • Describe how micelles enter epithelial cells, and are reconverted to TG • Explain how TG plus apoproteins and other lipids form nascent chylomicrons that exit cells • Describe role of HDL lipoproteins to mature the nascent chylomicrons, and breakdown of particles

  7. I. Digestion of dietary triacylglycerols • I. Digestion of dietary triacylglycerols • Major fat in diet (storage of lipids plants, animals) • Lipases digest to 2-monoacylglycerol (2-MG) • Bile salts emulsify fat in small intestine • Bile salts derived from cholesterol Fig. 1 fatty acids in triacylglycerol Fig. 2, a bile salt

  8. Digestion, absorption • Digestion of dietary triacylglycerols: • Lipases digest • Bile salts emulsify, colipases aid lipases • TG reform in epithelium Fig. 3:TG, triacylglycerol; BS, bile salt, FA, fatty acid 2-MG, 2-monoacylglycerol

  9. Enzymes degrade lipids • Enzymes degrade lipids: • Lipases cleave C1, C3 of TG • Cholesterol esterase removes FA • Phospholipase degrades phospholipid Figs. 5,6

  10. Absorption • Absorption into intestinal epithelial cells: • FA, 2-MG, cholesterol, other lipids, BS in micelles • Lipids absorbed through microvilli, not bile salts • Bile salts are recycled • Short, med-chain FA absorb directly epithelium, enter bloodstream bound to serum albumin Figs. 3,6

  11. III. Chylomicrons • III. Chylomicrons • TG are resynthesized in intestinal epithelia • ATP activates FA → FA-CoA (in Smooth ER) • Apoproteins and other lipids bind • [synthesis of TG in liver, adipose starts with phosphatidic acid] Fig. 7

  12. Blood lipoproteins • Blood lipoprotein particles transport lipids: • Chylomicrons – produced in intestinal cells from dietary fat; carry TG in blood • VLDL – produced from liver mainly from dietary carbohydrate; carries TG in blood • IDL - produced in blood (remnant of VLDL) • LDL – produced in blood (remnant of IDL after TG digestion; high concentration of cholesterol; • endocytosed by liver, other tissues (LDL receptor) • HDL – produced in liver, intestine; exchanges proteins and lipids with other lipoproteins; returns cholesterol to liver

  13. Transport of lipids in blood • Transport of lipids uses lipoprotein complexes: • Lipids are not soluble in water; would coalesce • Phospholipids, protein on outside; hydrophobic inside • Cholesterol esters have fatty acid moiety • Ex. VLDL from liver (very-low density lipoprotein) Fig. 8 Fig. 33.10

  14. Nascent Chylomicrons • Nascent chylomicrons from dietary TG: • SER enzymes reform the TG • Least dense lipoproteins (lot of TG) • Proteins made on RER • Apoprotein B-48 Figs. 9,10

  15. Apoprotein B gene • B-apoprotein gene encodes two polypeptides: • ApoB-100 in liver VLDL particles • ApoB-48 in intestinal cells is only 48% length • RNA editing changed codon in mRNA Fig. 11

  16. IV. Lipoprotein particles transport dietary lipids in blood • Additional proteins form mature chylomicrons: • ‘Nascent chylomicrons’ exocytosed into blood • Acquire additional proteins from HDL particles • ApoCII binds enzyme LPL on cell surfaces • Lipoprotein lipases • ApoE binds receptor on liver • cell for recycling Fig. 12

  17. Fate of chylomicrons • Chylomicrons from dietary lipids: • matured in blood by HDL particle interaction • Are digested at capillary wall by LPL (CII activates) • Insulin stimulates more LPL on surface • FA binds albumin in blood • FA into muscle (energy) • FA into adipose (store) • Remnants bind liver • through ApoE-receptor • Recycled in lysosome Fig. 13

  18. Olestra • Olestra is artificial fat substitute • Tastes like fat, not metabolized • sucrose with fatty acyl groups esterified on OH • resistant to hydrolysis by lipases, passes through • carries lipid-soluble vitamins

  19. Key concepts: • Key concepts: • Triacylglycerols are major fat source in diet • Lipases perform digestion, bile salts emulsify • Free fatty acids and 2-monoacylglycerol form • Micelles transport components into intestinal cells • Nascent chylomicrons are reformed from TG, cholesterol and apoB-48 protein; pass into blood • HDL particles contribute additional proteins to form mature chlymicrons • LPL (lipoprotein lipase) on cell surface cleaves TG and cells gain FA; remnants recycled in liver

  20. Review question • Type III hyperlipidemia is caused by a deficiency of apoprotein E. Analysis of the serum of patients with this disorder would exhibit which of the following? • An absence of chylomicrons after eating • Above-normal levels of VLDL after eating • Normal triglyceride levels • Elevated triglyceride levels • Below-normal triglyceride levels

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