Metabolic responses to high-intensity exercise

1. Metabolic responses to high-intensity exercise

2. Substrates for high-intensity exercise • Phosphocreatine • Relatively small amounts in cell • 70-80 mmol/kg vs ~25 mmol/kg for ATP • During high intensity exercise • ATP requirement may be 8-10 mmol/kg/sec • Thus, ATP stores would last ~2-3s • PCr ~ 8-10s • Onset of high-intensity exercise • Momentary rise in ADP • Stimulates Creatine kinase Rx Seconds

3. Phosphocreatine • Notice how PCr degradation • Highest in the first couple of seconds • Falls off rapidly after ~5-10s • Thus, • PCr degradation contributes most significantly to ATP replenishment in the first couple of seconds of high-intensity exercise • This contribution falls off rapidly after ~10s

4. Glycogenolysis and glycolysis • After the first 10s of high-intensity exerise • Something else must contribute to ATP resynthesis • Anaerobic metabolism • Notice how anaerobic metabolism increases as PCr metabolism decreases • Integrative nature of metabolism • As Ca2+ increases and metabolites start to accumulate (ADP, AMP, IMP, NH3 and Pi) • Activates glycogenolysis Seconds

5. Glycogenolysis • Increased rate noted with the following circulatory occlusion • Thus, when oxygen is not allowed to get to the muscle, PCr metabolism increases and Pi rises • This increase in Pi has been shown to be a powerful activator of glycogenolysis • Other factors that can regulate rate of glycogenolysis • Increases in AMP and IMP • Thus when Ca2+, AMP and Pi increase during high intensity activity • Glycogenolysis is activated

6. Anaerobic glycolysis Energy provision from anaerobic glycolysis peaks ~45s Typically still provides about 50% of the ATP requirements at 2 minutes Why does glycolytic rate fall off after ~45s? Glycogen depletion Not likely (these stores are still high at the end of maximal exercise pH fall reducing glycolytic rate Also, not likely Overcome by build up of AMP May inhibit muscular contraction Fall in AMP Due to AMP deaminase converting AMP to IMP Seconds

7. Integration • High rate of ATP provision from PCr and anaerobic glycolysis can only occur for ~30-45s • The following is likely what happens • PCr can “buffer” falls in ATP from the onset of exercise until about 5-10s of work • The products of the ATPase (ATP → ADP + Pi), Creatine Kinase Rx (PCr + ADP ↔ ATP + Cr) and Adenylate kinase Rx (ADP + ADP ↔ ATP + AMP) all stimulate glycogenolysis/glycolysis • Inhibition of muscle contraction by fall in pH and fall in AMP (due to AK Rx) reduce ATP demand and supply Seconds

8. High intensity exercise >30s • Shortly after 30s of exercise • “non-aerobic” contribution to ATP supply falls off • Thus, oxidative metabolism contributes more and more as exercise duration increases

9. High intensity exercise >30s • Note also which substrate is contributing the most during only 30s of work • We are seeing a shift • ATP can cover the first 1-2s • PCr can cover most of the ATP demand up to ~5-10s • Glycolysis then picks up after that Hatched bar, ATP; diagonal lines, PCr; black, glycogen

10. High intensity exercise >30s • So, the contribution to ATP homeostasis appears to be a continuum • ATP can contribute for 1-2s (highest power output) • PCr can contribute for a further 5s or so (drop off in power output) • Anaerobic glycolysis can continue to contribute for exercise of greater length • However, power output falls considerably Seconds

11. Repeated bouts of exercise • Note the different response for first vs second bout • Incomplete PCr resynthesis between bouts • Note that while the fall in PCr degradation is about 33%, the fall in work was only ~8% • Faster activation of oxidative metabolism? • Oxygen uptake kinetics suggest this is true

12. Muscle fiber type effects • Type I vs. type II fibers • Note that type I fibers (hatched bars) exhibit a completely different response • Type I fibers have • Greater capillary density • Greater mitochondrial volume • Thus, they can activate oxidative metabolism much more quickly than fast twitch • B-GPA

13. Fatigue • Inability to maintain a given power output • Complex, multifactorial process • Mechanism differs for different durations of exercise

14. Disruption of energy supply • Fatigue during short-duration, maximal exercise • Decline in ATP production • Reduced contribution of PCr and immediate energy system • Note that even with circulation occluded, glycogen does not even approach zero • So, muscle must switch from PCr-ATP to anaerobic glycolysis • Power output falls • Leads to greater lactic acid levels • Thus, the rate at which ATP is regenerated falls and thus, so does power output

15. Fatigue due to product inhibition • Lactic acid • Directly inhibits muscle force production • Most sprint animals have exceptional muscle buffering capacities

16. Fatigue • Muscle force production is reduced by • A reduction in PCr • Reduction in pH • What else? • Accumulation of Pi • Notice how the fall in PCr is mirrored by the rise in Pi

17. Fatigue due to other factors • Calcium • Calcium release from the Sarcoplasmic reticulum necessary for force production • Force increases/decreases with calcium • Over time calcium release is reduced • Reduced re-uptake into SR • Increased calcium binding • Parvalbumin