Carbohydrate Metabolism During Exercise

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

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

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

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

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

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])

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

Insert fig 2.1

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

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

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

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

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

PHOS Oh no, not again!!!

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

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

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

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

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

Some other proposed modulators Inhibitors Citrate Phosphoglycerate Phophoenolpyruvate Mg2+

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

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

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

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

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?

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

GLUT proteins

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?

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

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??

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

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.

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

Lactate Production

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

The Cori cycle: lactate as a fuel source

Muscle fuel sources in highly trained endurance athletes

Contributions of four energy sources over prolonged time in endurance athletes