Oxidative Phosphorylation The Mighty Mitochondria The Mighty

Oxidative Phosphorylation
The Mighty Mitochondria
• What’s the job of each portion of the mitochondria?
The Mighty Mitochondria
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The Mighty Mitochondria
The Mighty Mitochondria
Acetic acid
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& acetyl co‐A
Fig 6.8
By‐product tally?
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Key Regulators of Krebs?
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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?
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Holloszy et al., 1970
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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
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So, what controls the ETC?
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A classic: John O. Holloszy (1967—JBC)
• Major findings??
– Types of Δs
111%
86%
140%
62%
81%
68%
60%
Metabolic Adapatations in Humans
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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
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Beta‐oxidation & Fats
Function of lipids???
Key terms
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Mobilization
Circulation
Uptake
Activation
Translocation
Beta‐oxidation
Mitochondrial oxidation
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Adipose Tissue Lipolysis
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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
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Regulation of Regional Lipolysis by Catecholamines
Effect of Endurance Ex trg on IMTG lipolysis
What’s the next step?
• Mobilization
• Circulation
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Uptake
Activation
Translocation
Beta‐oxidation
Mitochondrial oxidation
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FA Transport
Fatty acid uptake
Fig. 7‐6
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Translocation
Malonyl Co‐A
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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
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Beta‐oxidation tidbits
So, how does the math work out??
Randle Cycle: Glu‐Fatty Acid Cycle
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Cross‐Over Concept
What metabolically is CAUSING the crossover???
Skeletal Muscle
Glyocogenolysis
What happens w/ endurance trg & the crossover?
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How does the crossover & GLU‐FA cycle fit together?
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Fig 3
Alborg fig 2
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How do we regulate bld [GLU]?
To ↑ “reserves” of GLU for ↑d demand w/ exercise
Postprandial vs. Fasted
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Adipose cell
↑NE, EPI, glucagon
triglyceride
↑cAMP
Glucose entry into cell
Insulin
3FFA +
Glycerol phosphate
3 FFA +glycerol
Liver
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Trained
Untrained
During submaximal ex
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Insulin & Trg
Glucagon & Trg
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