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 Thus,
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 What else?
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