CHAPTER 24: Lipid and Amino Acid Metabolism

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1 CHAPTER 24: Lipid and Amino Acid Metabolism Describe the digestion of fats and proteins utline the steps in the β-oxidation of fatty acids and describe the circumstances of ketone body production Describe the pathway of fatty acid synthesis Explain the nature of transamination and oxidative deamination and the importance of the urea cycle Understand how the carbon skeletons of amino acids are metabolized FAT DIGESTIN, ABSRPTIN, & DISTRIBUTIN PRTEINS AMIN S CARBHYDRATES SIMPLE SUGARS FD FATTY S & GLYCERL DIETARY & ILS Lipase Function C GALL BLADDER HC C C LIPPRTEINS VILLUS LACTEAL THRACIC DUCT SMALL INTESTINE Bile Salts MNGLYCERIDES FATTY S PANCREAS Lipase HC LIPASE 2H 2 H HC C H TRIGLYCERIDE MNGLYCERIDE TRIGLYCERIDES FREE FATTY S HC Membrane lipids, proteins LIPID TRANSPRT Lipoprotein compositions (%): LIPPRTEINS PRTEIN LIPID CARG CHLESTERL Chylomicrons VLDL LDL Phospholipid Protein Triglyceride Cholesterol esters PHSPHLIPID MNLAYER Cargo consists of triglycerides and/or cholesterol esters. verall composition varies with lipoprotein type. TAG s FRM FD THRU INTESTINES T TISSUES TAG s FRM LIVER T ADIPSE CHLESTERL FRM LIVER T TISSUES HDL CHLESTERL T LIVER FRM TISSUES Page 24-1

2 Exercise and HDLs FAT MBILIZATIN Cholesterol C HC C C ADIPSE CELL LIPASE 3H 2 H HC VLDL Triglycerides for catabolism in muscle HDL HC HC H HC H Complete hydrolysis of of stored triglycerides with transport of of the resulting fatty acids and glycerol in in the bloodstream 24.4 FATTY DEGRADATIN Sequential removal of 2-carbon fragments from carboxyl end of chain Production of one acetyl CoA for every 2- carbon fragment LCATIN: mitochondrial matrix β-xidatin 16 FATTY SPIRAL Fatty Acid CoA UTER MEMBRANE CoA Carnitine INNER MEMBRANE 16 * * ENERGY UTPUT FAT (MW 891) Glycerol 20 ATP 3 Stearate 3(146 ATP) 458 ATP 1 ATP/2g GLUCSE (MW 180) 38 ATP 1 ATP/5g 24.6 KETNE BDIES RATE(glycolysis) >> RATE(β-oxidation): pyruvate feeds citric acid cycle as acetyl CoA and oxaloacetate RATE(glycolysis) << RATE(β-oxidation): citric acid cycle slows, since only acetyl CoA produced Excess acetyl CoA from β-oxidation used in synthesis of alternative fuels: KETNE BDIES KETGENESIS Synthesis of of ketone bodies from acetyl CoA Page 24-2

3 2 C 2 CH 3 C CH 3 Acetone CoASH CH 3 C C Acetoacetate CH 3 C C SCoA Acetoacetyl CoA NADH, H Weak acids NAD H H 2 CoASH CH 3 C C H β-hydroxybutyrate KETSIS Pathological metabolisms with reduced glycolysis: High-protein liquid diets Starvation Diabetes Accumulation of ketone bodies lowers blood ph, leading to KETSIS 24.7 FATTY SYNTHESIS LCATIN: cytoplasm Intermediates bound covalently to acyl carrier protein (ACP) NADPH (phosphorylated NADH) cofactor reducing agent Sequential addition of 2- carbon fragments to ACPbound intermediates Reaction Chambers (3 sets of active sites in each) Fatty Acid Synthase CH 3 C S ACP ACETYL ACP C C S ACP MALNYL ACP CH 3 C C S ACP CH 3 C S ACP NADPH BUTYRYL ACP NADP NADPH H 2 C 2 ACP NADP Triglycerides STRAGE MBILIZATIN (Synthesis) (Hydrolysis) 24.8 AMIN METABLISM FD Fatty Acids & Glycerol PRTEINS CARBHYDRATES SYNTHESIS β-xidatin GLYCLYSIS AMIN S SIMPLE SUGARS FATTY S & GLYCERL Page 24-3

4 DIGESTIN DIETARY PRTEIN 24.9 CATABLISM of AMIN S STAGE 1: Transfer of α-amino group VILLUS CAPILLARY AMIN PL SMALL INTESTINE STMACH Pepsin HCl PLYPEPTIDES PANCREAS Trypsin STAGE 2: Removal and oxidation of α-amino group STAGE 3: Detoxification of ammonium ion Location: LIVER (cytoplasm and mitochondria) NH 2 TRANSFER and REMVAL: C C C α-ket- GLUTARATE NH 4 C H C R NH 3 AMIN XIDATIVE DEAMINATIN TRANSAMINATIN C H C C GLUTAMATE NH 3 C C R α-ket CARBN SKELETN CATABLISM NITRGEN EXCRETIN WHY: NH 4 ( NH 3 ) accumulation (HYPERAMMNEMIA) shuts down oxidative deamination GLUTAMATE accumulates and lowers concentration of α-ketglutarate Reactions of citric acid cycle slow ATP synthesis slows 2ATP 2ADP 2P i NH 4 HC 3 H 2 N C CARBAMYL PHSPHATE P C CARBHYDRATES ACETYL CoA CoA H 2 N RNITHINE C NH 3 C NH 2 H 2 NH HN C NH 2 C ARGININE C ASPARTATE ATP AMP PP i PRTEINS TRANSAM N XID DEAM N CYCLE CITRIC CYCLE 2 C 2 XIDATIVE PHSP N H 2 ADP, P i ATP Page 24-4

5 24.10 CATABLISM of AMIN CARBN SKELETNS Skeletons of all 20 amino acids are degraded into or acetoacetyl CoA (KETGENIC S) or Pyruvate or citric acid cycle intermediates (GLUCGENIC S) All degraded forms of of carbon skeletons are part of of or or enter the citric acid cycle AMIN BISYNTHESIS LCATIN: liver Results in production of nonessential amino acids. Key starting materials: Glycolysis intermediates Citric acid cycle intermediates Phenylalanine Asp Asn Pyruvate Ala Glu C C CITRIC CYCLE C XAL ACETATE C 2 C 2 NH 4 C C H C NH 3 C C C GLUTAMATE α-ket- GLUTARATE Glu GLYCLYSIS C CH H P 3-PHSPHGLYCERATE PHENYLALANINE Phe Ser Tyr Cys Gly Arg Pro Gln PKU PKU if if necessary enzyme (Phe (Phehydroxylase) missing Page 24-5