Oxidative Phosphorylation The Mighty Mitochondria • What’s the job of each portion of the mitochondria? The Mighty Mitochondria 1 The Mighty Mitochondria The Mighty Mitochondria Acetic acid 2 & acetyl co‐A Fig 6.8 By‐product tally? 3 Key Regulators of Krebs? • • • • • • • PDH NADH2 Low oxaloacetate Acetyl Co‐A ATP Pyruvate & Ca++ IDH Maybe you’d like the stimulators & inhibitors in a chart form? Product Stimulator Inhibitor Citrate synthase Isocitrate dehydrogenase ketagluterate dehydrogenase Succinate dehydrogenase What about Exercise Training? 4 Holloszy et al., 1970 5 What’s the main function of the ETC? The Electron Transport Chain Complex/Enzyme Job Complex I—NADH dehydrogenase Complex II—Succinate Dehydrogenase Complex III—Cyctochrome bc1 Complex IV—Cyctochrome c oxidase 6 So, what controls the ETC? 7 A classic: John O. Holloszy (1967—JBC) • Major findings?? – Types of Δs 111% 86% 140% 62% 81% 68% 60% Metabolic Adapatations in Humans 8 Time course of adaptations • Hickson 1981, JAP: • Coyle 1984 JAP: SEVERE detraining study: Peripheral adaptations that ↑ O2 utilization by muscles Training Induced Δs in Mito – How does this happen?? Essig ESSR 1996 9 Beta‐oxidation & Fats Function of lipids??? Key terms • • • • • • • Mobilization Circulation Uptake Activation Translocation Beta‐oxidation Mitochondrial oxidation 10 Adipose Tissue Lipolysis 11 Sources of FA during exercise (Gluteal/Femoral) Regulation of Lipolysis during exercise Source of FA for Ox by skeletal muscle during exercise‐ effect of intensity 12 Regulation of Regional Lipolysis by Catecholamines Effect of Endurance Ex trg on IMTG lipolysis What’s the next step? • Mobilization • Circulation • • • • • Uptake Activation Translocation Beta‐oxidation Mitochondrial oxidation 13 FA Transport Fatty acid uptake Fig. 7‐6 14 Translocation Malonyl Co‐A 15 • • • • • Mobilization Circulation Uptake Activation Translocation • Beta‐oxidation • Mitochondrial oxidation Fatty Acyl CoA Fatty acyl CoA Fatty acyl CoA dehydrogenase dehydrogenase FAD FADH2 Enoyl CoA Enoyl CoA Enoyl CoA hydrase hydrase H2O ‐ Hydroxyacyl CoA Hydroxyacyl CoA Hydroxyacyl CoA dehydrogenase dehydrogenase NAD NADH2 ‐Ketoacyl CoA Rate limiting step Rate limiting step CoA‐SH Inhibited by high Inhibited by high ‐ ‐ketothiolase ketothiolase Acetyl CoA Acetyl CoA Acetyl CoA + Fatty Acyl Co A Krebs 16 Beta‐oxidation tidbits So, how does the math work out?? Randle Cycle: Glu‐Fatty Acid Cycle 17 Cross‐Over Concept What metabolically is CAUSING the crossover??? Skeletal Muscle Glyocogenolysis What happens w/ endurance trg & the crossover? 18 How does the crossover & GLU‐FA cycle fit together? 19 Fig 3 Alborg fig 2 20 How do we regulate bld [GLU]? To ↑ “reserves” of GLU for ↑d demand w/ exercise Postprandial vs. Fasted 21 Adipose cell ↑NE, EPI, glucagon triglyceride ↑cAMP Glucose entry into cell Insulin 3FFA + Glycerol phosphate 3 FFA +glycerol Liver 22 Trained Untrained During submaximal ex 23 Insulin & Trg Glucagon & Trg 24 25
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