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MSU BMB 462 - Lect+08+and+09+-+Lipid+Catabolism

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Slide 1Lipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismLipid CatabolismPage 1Lipid CatabolismLehninger Readings Chapter 17 pages 667-688Lipids serve as a major source of cellular energy. At the end of this section you should be able to describe the processes your body uses to extract energy from the lipids you consume and from lipids stored in your body.Student Learning ObjectivesYou should be able to:1) Tell the "Big Picture" story of how lipids are catabolized.2) Explain both in terms of cellular packaging, kJ/g dry weight, and total energy why fatty acids are an important energy reserve in the human body.3) Describe the digestion and absorption of lipids including emulsification, hydrolysis, and transfer to the bloodstream. 4) Describe the structure of chylomicrons and their role in transport of lipids.5) Describe the functions of dietary lipases, hormone-sensitive lipase and lipoprotein lipase in metabolism of fatty acids.6) Compare and contrast the degradation and transport of dietary triacylglycerols and triacylglycerols in adipose tissue. 7) Describe how glycerol from triacylglycerol is catabolized.8) Explain how fatty acids are activated and transported into the mitochondria.9) Connect -oxidation to other catabolic processes used to generate energy.10) Describe the steps, enzymes, cofactors, and metabolic intermediates involved in the -oxidation of fatty acids, their localization, and the regulation of the process.11) Compare and contrast -oxidation with the oxidation of succinate to oxaloacetate in the TCA cycle. 12) Calculate the number of ATPs produced from the degradation of saturated and unsaturated even-number fatty acid.13) Know the special requirements for the oxidation of unsaturated and odd-number fatty acids.14) Describe -oxidation of fatty acids in peroxisomes.15) Compare and contrasts -oxidation of fatty acids in peroxisomes and mitochondria.16) Describe ketone bodies and the intermediates and reactions involved in their metabolism17) Explain the purpose of ketone bodies in metabolism including sites of production and utilization.18) Explain the relationship between acetyl-CoA and ketone bodies.19) Describe ketosis and relate this to the fact that humans lack the glyoxylate cycle.20) Explain why starvation increases the production of ketone bodies and their use as an energy source.Page 2Lipid Catabolism•Energy storage in lipids–Oxidation State of Carbon–Storage Form–Chemical ReactivityBuilding block Storage in humans EnergyThe structural/physical/chemical properties of each drive its functions-amino acidsNo specific storage form17 kJ/gnucleotidesNonefatty acidLipid Droplets which are anhydrous38 kJ/g monosaccharidesGlycogen which is hydrated16 kJ/g1) Tell the "Big Picture" story of how lipids are catabolized.2) Explain both in terms of cellular packaging, kJ/g dry weight, and total energy why fatty acids are an important energy reserve in the human body.Page 3Lipid Catabolism•Lipid digestion, absorption and transport in mammals–Bile salts–Intestinal lipases–Absorption–TAG Synthesis–Chylomicrons•Structure•Function–Lipoprotein lipases•Role of apoC-IIFigure 17-1Figure 17-23) Describe the digestion and absorption of lipids including emulsification, hydrolysis, and transfer to the bloodstream. 4) Describe the structure of chylomicrons and their role in transport of lipids.5) Describe the functions of dietary lipases, hormone-sensitive lipase and lipoprotein lipase in metabolism of fatty acids.Page 4•Mobilization of TAGs from adipose tissue–Lipid droplets structure–Regulation–Perilipin–Activation and Role of Lipases–Serum albuminLipid CatabolismGlycerolL-Glycerol 3-phosphateDihydroxyacetone phosphateATP NAD+NADHADPGlycerol KinaseGlycerol Phosphate Dehydrogenase•Glycerol Metabolism–Recycling to make glycerolipids.–Conversion to a glycolytic intermediate for energy.Figure 17-3Figure 17-46) Compare and contrast the degradation and transport of dietary triacylglycerols and triacylglycerols in adipose tissue. 7) Describe how glycerol from triacylglycerol is catabolized.Page 5Lipid Catabolism•Fatty Acid Catabolism–Activation by fatty acyl-CoA synthetase•Mechanism•Energetics–2 high energy phosphate bonds (2 ATP Equivalents) used per fatty acid activated!Figure 17-5Page 6Lipid Catabolism•Fatty Acid Catabolism–Carnitine Shuttle•Overall purpose•Carnitine Acyltransferase I•Acyl-carnitine/Carnitine Transporter•Carnitine Acyltransferase II•RegulationFigure 17-68) Explain how fatty acids are activated and transport into the mitochondria.Page 7Lipid Catabolism•Fatty Acid Catabolism–Overview of Fatty Acid -oxidation•Oxidation of the -carbon•Removal of Acetyl-CoA (2 carbons)•Oxidation of Acetyl-CoA by the TCA cycle•E.T.C. and Ox. Phos. with reduced cofactorsFigure 17-79) Connect -oxidation to other catabolic processes used to generate energy.Page 8Lipid Catabolism•Fatty Acid Catabolism–The 4 steps in -oxidation •Dehydrogenation (oxidation)•Hydration•Dehydrogenation (oxidation)•Thiolysis– Compare with TCA cycleFigure 17-8Figure 16-7 See also Figure 17-910)Describe the steps, enzymes, cofactors, and metabolic intermediates involved in the -oxidation of fatty acids, their localization, and the regulation of the process.11) Compare and contrast -oxidation with the oxidation of succinate to oxaloacetate in the TCA cycle.Page 9Lipid Catabolism•Fatty Acid Catabolism– Repeating the four steps–ATP yield Start with palmitateHow many rounds of -oxidation?How many FADH2 and NADH + H+ are produced during each round?How many FADH2 and NADH + H+ produced by complete -oxidation?How many acetyl-CoA are produced?How many FADH2 and NADH + H+ and GTP are produced by oxidation of 1 acetyl-CoA by the TCA cycle?How many FADH2 and NADH + H+ and GTP are produced by oxidation of all the acetyl-CoA from -oxidation of palmitate?How many FADH2 and NADH + H+ and GTP are produced by complete oxidation of palmitate by -oxidation and the TCA cycle?P/O for FADH2 is 1.5 and NADH + H+ is 2.5. How many ATP are produced by complete oxidation of palmitate? (don't forget to subtract 2 ATP for activation of palmitate by Acyl-CoA synthetase)Figure 17-812) Calculate the number of ATPs produced from


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