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Transcript
Lipid Metabolism During Exercise Introduction 1.) Energy Density 2.) Polar explorers/sled dogs American Indians (pemican) 3.) Migrating fish and birds 4.) 3 sources plasma FFA from adipocytes (large > 50,000 kcals) intramuscular TG (2,000 -3,000 kcals) plasma TG (very small role during exercise in humans) 5.) Destabilizing effect on membranes High IMTG (obesity, type-II diabetes) linked with insulin resistance in muscle. Storage and Mobilization of Triglycerides Adipose Tissue Lipolysis • Glycerol release, no Glycerol Kinase in adipocyte or muscle – , , Insulin, Lactate re-esterification FFA Passive vs. Carrier-mediated Fatty acid binding protein (FABP) EPI Insulin B increases cAMP Alpha decreases cAMP Insulin activated PDE thus decreases cAMP Hormone Sensitive Lipase • Phosphorylated by Protein Kinase A – becomes active – catabolic in nature Mechanism: Epinephrine binds to receptor on adipocyte this causes activation of AC – increase in cAMP cAMP activates Protein Kinase A Insulin counteracts this deactivates Protein Kinase A via activation of PP-1, activates PDE which decreases cAMP Regulation of HormoneSensitive Lipase PKA C C C OH OH OH O HO C C C C Dehydration Synthesis C O C C O C C C C H.S. Lipase Triglyceride C C C OH OH OH Glycerol O + HO C C FFA C Hormone Sensitive Lipase Adrenoceptor Blockade Schematic FFA/Blood Glycerol at Rest and Exercise Exercise 50% Exercise 50% Notice the magnitude of the change in FFA vs. glycerol FFA Transport to Muscle Cells • Fatty Acids from adipose – transported in blood via Albumin – 3 per – brought to muscle cell at fatty acid binding receptor proteins – taken into muscle cell Triglycerides in blood (chylomicrons and VLDL) broken down by lipoprotein lipase in capillary of the muscle before being taken into cell FA transporters 1. FABPpm 2. FATP 3. FAT/CD36 Higher in ST vs. FT Training has been shown to increase the amount of FA transporters in the PM. Fatty Acid Transport Into Mitochondria • FA can’t cross mitochondrial membrane Must use carnitine acyl transferase (CAT) system CAT I located in outer wall Binds carnitine to FA, enabling it to pass inner mem. RATE LIMITING STEP IN FAT UTILIZATION! CAT II located in mitochondrial matrix removes carnitine from FA Step 1: Fatty Acid Transport Into Mitochondria (cont.) (Acyl CoA synthase – in outer wall) FFA Fatty Acyl CoA Step 2: Fatty Acyl CoA CAT I Fatty Acyl Carnitine Step 3: Fatty Acyl Carnitine CAT II Fatty Acyl CoA (inside mitochondrial matrix) *With training, number of mitochondria, CAT I , fat use with exercise. -Oxidation Cycle *No rate limiting steps in -Oxidation cycle! Rate limiting step occurs with CAT I.* Step 1: O C C C C OH FFA Acyl CoA Synthase ATP CoAS H AMP H2 O H H O C C H H C ~S CoA Fatty Acyl CoA Step 2: H H O C C C ~S CoA H H **Recall: Fatty Acyl CoA is transported into mitochondria via CAT I & II complex** Fatty Acyl CoA FAD Acyl CoA Dehydrogenase (trans dehydrogenase rx) FADH2 H O C H C C ~S CoA Enoyl CoA Step 3: H O C C C ~S CoA H Enoyl CoA H2O (add to make 2° -OH) Enoyl CoA Hydrase OH H O C C H H C ~S CoA L-Hydroxyacyl CoA Step 4: OH H O C C C ~S CoA H H L-Hydroxyacyl CoA NAD L-Hydroxyacyl Dehydrogenase (oxidize 2°-OH to keto) NADH + H ( Carbon) O H O C C C ~S CoA () H Keto Acyl Step 5: O H O C C C ~S CoA () H Ketothiolase O C ~S CoA Acyl CoA Keto Acyl -oxidation? CoASH () carbon oxidized from saturated to keto NAD & FAD are reduced! H O H C H C ~S CoA Acetyl CoA (on to Krebs cycle) Energy yield of Palmitic Acid (16 C - FS - FA) C C C C C CC C C C C C C C C C 7 FADH2 x 2 = 14 7 NADH2 x 3 = 21 8 Acetyl CoA x 12 = In CAC: 3 NADH 1 FADH 1 ATP Activation with Co ASH 96_ 131 __-2 129 ATP ATP AMP Glycerol C C OH OH C OH Glycerol ATP ADP Glycerol kinase only in liver C H C C OH OH O~P Glycerol 3-P (Glycerol P NAD dehydrogenase) NADH2 C C C DHAP OH O O~P gluconeogenesis glycolysis Muscle Glycogen vs. FFA Expenditure Substrates Providing Energy Plasma Triacylglycerol VLDL - 50% LDL FABP 1. 2. 10% of fat use Slow twitch Fast twitch 3. LPL activity ~ ~ 1 hr of exercise 2 - 8 hr 2x LPL Chylomicron - 85% FFA - Albumin Blood 80% H2O FFA Tri C | C | C In VLDL and chilomicrons Lipoprotein Lipase Triglyceride Breakdown for Energy Step 1: C C O C O C C C C Triglyceride HSL C C OH OH C OH Glycerol O + HO C C FFA C C Both muscular contraction and Insulin translocate FAT/CD36 from intracellular sites to plasma membrane. Recent studies have found the effects of insulin and muscular contraction to be additive, suggesting separate ICF pools of FA transporters. Beta oxidation of FA in the mitochondria increases acetyl-CoA and citrate concentrations. AMPK prevents formation of malonyl Co-A, which is a allosteric inhibitor of CAT I, thus AMPK increases FFA uptake into mitochondrial matrix Triglyceride Formation C OH C C OH OH Glycerol + O HO C C C C FFA H2O (Dehydration Synthesis) C C O C O C C C Triglyceride C