Metabolic responses to high-intensity exercise

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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