Metabolic responses to prolonged exercise

Substrates for prolonged exercise Prolonged exercise – min. –Typically between lactate threshold and critical power (50-80% Vo 2 max) Intensities below this are limited by boredom Intensities above this quickly lead to fatigue –ATP requirement ~2.5 mmol/kg/s –About ¼ of that required during high intensity exercise –CHO the predominant fuel source

Substrates for prolonged exercise Onset of prolonged exercise –Lag phase in oxidative phosphorylation PCr and anaerobic glycolysis make up the difference in terms of ATP production Maximum rate of ATP provision from CHO oxidation; 2-3 mmol/kg/s (So, CHO oxidation can cover this type of exercise) Muscle/liver stores of glycogen sustain ~ min of exercise Maximum ATP rate from hepatic glycogen; ~1 mmol/kg/s Maximum rate from fat; ~1 mmol/kg/s However, max ATP rate from CHO and Fat together; ~2 mmol/kg/s –This is increasingly likely as exercise duration increases

Integration of CHO and fat oxidation Clearly, this happens at all marathon distances and above –Rate limiting step of CHO oxidation Pyruvate Dehydrogenase –Inner mitochondrial membrane –3 enzymes –2 regulatory enzymes »PDH kinase (deactivates); activated by high ATP/ADP, Acetyl-CoA/CoA and NADH/NAD + »PDH phosphatase (activates); activated by low ATP/ADP, Acetyl- CoA/CoA and NADH/NAD + and Ca 2+ –Thus, work activates PDH, rest inactivates PDH

Acetyl group buffering If acetyl-CoA were to increase –Inhibit PDH and thus, glycolysis –CoA pool may decrease Needed in PDH and alpha- ketoglutarate DH Rx –Carnitine + Acetyl-CoA →Acetylcarnitine + CoA –Acetylcarnitine levels increase in parallel with exercise intensity

Muscle glycogen stores ~350 mmol/kg Hard to change Thus, CHO availability will limit performance of > min Many studies have shown the following about CHO: High CHO vs Low CHO High CHO clear increase in performance CHO loading Increases performance CHO replacement during exercise Increases performance So, for the best performance in prolonged athletics, CHO should make up the bulk of your diet Muscle carbohydrate availability

CHO-loading Modified regimen –50% CHO and moderate exercise for 3 days –3 days of declining exercise and 70% CHO Classical method –Prolonged strenuous exercise and a high fat/protein diet for three days while continuing to train to deplete glycogen stores –90% CHO diet for three days with light or no activity As both are equally effective, the modified approach is more often used

Liver CHO availability, diet and exercise Liver glycogen stores –Sensitive to diet 1 day of starvation to deplete glycogen stores 1 day of high CHO intake can double liver glycogen stores (~500 mmol/kg) –Reduced by exercise ~90 min at 60% VO 2 max –When liver glycogen falls Blood sugar levels fall Fatigue

CHO ingestion immediately prior to exercise Ingestion of a 75g CHO meal ~30 min prior to exercise resulted in –Transient rise in blood glucose –Large insulin response Hypoglycemia fatigue To avoid rebound hypoglycemia –Small amount of CHO just before exercise

CHO ingestion during exercise Studies have shown –Maintenance of blood glucose levels Reduces muscle glycogen utilization Increases performance How? –Type I fibers Reduced muscle glycogen usage –Hexokinase activity increased »As muscle glycogen is depleted Presumably this indicates greater usage of blood glucose Fat cannot supply ATP at a fast enough rate –Reduced liver glycogen utilization

Increased fat availability prior to exercise Low intensity exercise –Low CHO diet (3%) –40 km/day walking for 4 days –No subjects became hypoglycemic –All subjects completed the exercise task Fat contributed to ATP demand of exercise, liver glycogenolysis/gluconeogenesis contributed to maintenance of blood glucose –However, fat loading not necessary Plenty available CHO becomes main fuel source when exercise intensity rises above a walk

caffeine Caffeine ingestion prior to endurance exercise has been posited as an ergogenic aid –3-9 mg/kg (several cups of strong coffee) –Increased FFA mobilization –Suggested that caffeine’s effect was due to increased fat availability This does not make a lot of sense (Why?) –More likely Direct effect on CNS More efficient excitation/contraction coupling –Perhaps through improved calcium re-uptake

Fatigue Inability to maintain a given power output –Exact mechanisms by which CHO depletion cause fatigue Unclear –Hypotheses CHO depletion causes a reduction in the ATP resupply –TCA intermediates decrease with CHO depletion –ATP falls and ADP and IMP rise when CHO depletion occurs

Effect of heat on ATP homeostasis Body temperature –98-100°F ( °C) –During exercise Core temp can rise to ~40°C (~104°F) in humans and as high as 44-46°C ( ) in dogs, horses and camels When heat loss and gain are equal –Thermal balance

Fatigue due to Heat Heat gain factors –Metabolic heat production –Convective heat gain –Conductive heat gain –Radiant heat gain Heat loss –Convective heat loss –Conductive heat loss –Radiant heat loss –Evaporative heat loss

Fatigue in the heat 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

Fatigue due to Heat Note what mild dehydration does to the HR response So, exercise in the heat –Increased HR for any given exercise intensity –Cardiac output may fall (why?) –Muscle blood flow falls –Thus, any given workload is perceived as greater