Carbohydrate Metabolism During Exercise

1. Carbohydrate Metabolism During Exercise

2. Importance of Carbohydrate Metabolism • Involved in resynthesis of ATP during high-intensity exercsise • Also provide substrate for Krebs/TCA cycle

3. Carbohydrate Depletion and Fatigue • Glycogen depletion or hypglycemia often associated with exercise fatigue • Glycolysis provides pyruvate which feeds into Krebs/TCA • If glucose is insufficient to fuel glycolysis, Krebs may be slowed as a result

4. Carbohydrate Supplementation Attenuates Fatigue • Ingestion of carbohydrates during prolonged exercise maintains intracellular concentration of Krebs intermediates • Also attenuates increased levels of IMP accumulation

5. Exercise Intensity Limited in the Absence of CHO • If lipid is the sole energy source, exercise above 50-60 % VO2max cannot be sustained

6. McCardles Disease as a Model • McCardles patients do not have PHOS • Cannot utilize glycogen as a fuel source • Exercise capacity only 50 % of predicted • Also greater ATP degradation • Elevated IMP levels compared to normals

7. Glycogenolysis • Glycogen breakdown is both exercise intensity and duration dependent • Glycogenolysis is most rapid during short duration exercise • Rate is exponentially related to intensity • (ie. Doubling intensity 60 % - 120 %VO2max results in squaring the rate [100 fold increase in this case])

8. As exercise proceeds, glycogneolytic rate decreases • Could be reduction in glycogen stores • remember previous exercise • Could be change in the levels of allosteric regulators of PHOS as a result of lower intensity • If duration is longer, intensity must be lower

9. Insert fig 2.1

10. Why is Glycogenolysis Higher with High Intensity Exercise? • For low intensity exercise, primarily type I fibers involved • As intensity increases, type II s are recruited • At maximal intensity all fibers are recruited • Type II fibres have greater glycogenolytic capacity

11. Is Glycogenolysis Confined to Exercising Muscle • In animals, prolonged exercise results in glycogen loss in non-exercising muscles • In humans the data is equivocal

12. Glycogenolysis in Non-exercising Muscle • For • Forearm lactate release in prolonged leg exercise • Lactate could not be accounted for by glucose uptake • Lactate release from legs during recovery from arm exercise • Muscle glycogen declined 20 % in non-exercising leg during 4 hours one-legged cycling @ 20 % VO2max

13. Against • No change in non-exercising muscle glycogen content after glycogen depleting exercise • No change in 2 hours of one-legged cycling • No change in deltoid content with 2 hours leg exercise @ 55% VO2max • 65% decline in VL glycogen content

14. Why would you want glycogenolysis in non-exercising muscles? • If glycogenolysis occurs, glucose can be broken down via glycolysis • Pyruvate may be converted to lactate which can then be released from non-exercising muscle • Lactate can be converted to glucose via gluconeogenesis • Maintains blood glucose

15. PHOS • Oh no, not again!!!

16. How does CHO intake affect PHOS activity? • In animals, elevated blood glucose decreases glycogen breakdown

17. Low Intensity Exercise • During low intensity exercise (50% VO2max) w/ 30 s sprints, elevated blood glucose attenuates glycogen breakdown • Hypoth-between sprints, high glucose promoted glycogen resynthesis • This led to reduced NET breakdown

18. High Intensity Exercise • At high intensity 70-75%, elevated blood glucose has no effect on glycogen levels • Still ergogenic, maintains blood glucose

21. Phosphofructokinase (PFK) regulation • Most important regulator of PFK activity is ATP • ATP can bind to PFK at two sites and alter its activity • Binds to catalytic site with high affinity • Can also bind to allosteric site

22. PFK cont’d • Binding to the allosteric site inhibits activity • So,… when [ATP] in the cell is high, PFK will be inhibited • no need for glycolysis, plenty of ATP • H+ can enhance ATP affinity for allosteric site • Provides feedback inhibition

23. Some other proposed modulators • Inhibitors • Citrate • Phosphoglycerate • Phophoenolpyruvate • Mg2+

24. Promoters • AMP and ADP • Pi • NH4+ • Fructose –2,6 diphosphate

25. Citrate • Probably not a major factor during short, intense exercise • Aerobic metabolism does not contribute greatly until later (>30 s) • Citrate probably does not accumulate within the 30-60 s time frame • May be a factor as Krebs and fat metabolism become more predominant

26. Promoters • ADP and AMP will accumulate rapidly at the onset of anaerobic exercise • Breakdown of PCr • H+ may be reduced at the onset of exercise • Removing the ATP induced inhibition

27. Hormonal Regulation of Glucose Metabolism • Under non-exercising conditions, insulin needed to stimulate glucose entry into cell • Is insulin needed during exercise? • Permissive amount?

28. Insulin Not Necessary During Exercise • During exercise insulin levels decline • Glucose transport is stimulated by exercise in the absence of insulin • Effects of exercise and insulin are additive • Different mechanisms?

29. GLUT 4 • Both exercise and insulin translocate GLUT 4 to the cell membrane • Different pools of GLUT 4? • Effects are synergistic

30. GLUT proteins

31. So, insulin is not necessary for glucose transport during exercise • But, exercise increases cellular sensitivity to insulin • Hyperinsulinemia at the onset of exercise results in rapid drop in blood glucose • Implications for competition meals?

32. Epinephrine • Effects on glucose uptake are equivocal at best, confusing at worst • Can’t say one way or the other • Epi will activate PHOS though • This will stimulate glycogenolysis and possibly elevate G-6-P, in effect reducing glucose uptake

33. Glycogen Availability • Inverse relationship between glycogen levels and glucose uptake • Leg glucose uptake directly related to percentage glycogen-empty muscle fibers • Also, inversely related to muscle G-6-P levels • Inhibition through G-6-P levels??

34. Blood Glucose Availability • Glucose uptake is elevated during exercise when blood glucose levels are high • During the latter stages of exercise, as blood glucose drops, glucose uptake also decreases • High rates of glucose uptake can be achieved late in exercise if blood glucose levels are maintained • Carbs not ergogenic if glycogen stores elevated

35. Glucose-Fatty Acid Cycle • Randall proposed that increased FFA oxidation resulted in citrate ,mediated inhibition of PFK • Resulting elevations in G-6-P inhibited hexokinase, glucose phosphorylation and uptake • Experimental results equivocal to this point • This may work in a test tube, but it’s hard to show physio.

36. Lactate Metabolism • Lactate originally believed to be a “waste” product of anaerobic glycolytic metabolism • More recently believed to participate in carbohydrate metabolism, serve as an energy source as well as metabolic regulator

37. Lactate Production

38. Factors Affecting Lactate Production • O2 availability • Classic pathological factor affecting lactate production (ischemia) • Rate of glycogenolysis and glycolysis • Diet • High CHO diet results in more lactate formation • Catecholamines

39. The Cori cycle: lactate as a fuel source

42. Muscle fuel sources in highly trained endurance athletes

43. Contributions of four energy sources over prolonged time in endurance athletes