Module 3 - Carbohydrate Metabolism Flashcards
Carbohydrates:
- What are they used for?
- When are they used?
- Used for energy or ATP generation needed by contracting muscles
- Key substrate during high intensity sprint type exercise, and during more prolonged exercise at a moderate- to high-intensity
Carbohydrate stores
note: endogenous is internal
- Body’s endogenous stores are not large
- Stored in liver and skeletal muscle as glycogen
- A glycogen particle in skeletal muscle can contain ~30,000 individual glucose molecules linked together via the core enzyme glycogenin
What happens to glycogen during exercise?
- Glycogen content of active contracting muscle cells is reduced
- Glycogen is broken down through glycogenolysis which releases the individual glucose molecules from the core glycogenin protein so it can be used by the muscle through glycolysis and aerobic processes to produce ATP needed for muscle contraction
Carbohydrate stored in skeletal muscle as glycogen
- % of body’s carbohydrate
- concentration in mmol/kg.DM
- 80% (~400g) of all body’s carbohydrate is found in skeletal muscle as glycogen
- Glycogen concentrations in skeletal muscle is 50-500mmol/kg.DM - depending on training status, prior exercise, dietary carbohydrate intake
Carbohydrate stored in the liver
- Higher concentration of glycogen than muscle
- Liver is smaller in mass (~1.5kg) compared to skeletal muscle (40-50% of body weight in healthy young men)
- Amount of liver glycogen is 100g or 10-15% of total carbohydrate stores
Apart from skeletal muscle and liver, the remainder of carbohydrate circulates in the…
…blood or plasma as glucose (5g)
- When required, the glycogen stored in the liver can be broken down and released into circulation to maintain blood glucose levels
What are the primary factors that affect the source of carbohydrate for use in the major energy systems which are responsible for the production or resynthesis of ATP?
1) exercise intensity
2) exercise duration
During high intensity sprint type exercise (95-100% VO2max above)
- The muscle prefers “muscle glycogen” as its main fuel source
During low intensity exercise (25% VO2max)
- Very little glycogen breakdown occurs
- Overall contribution of both glycogen and glucose only accounts for 10-15% of total fuel source
As exercise intensity increases…
- Both glucose and glycogen become increasingly important as energy substrates
- Contribution to total energy production rises to 70%+ (85% VO2max)
Figure: During exercise at intensity greater than 60% VO2max
- Blood glucose and muscle glycogen are primary fuels oxidised to produce ATP
- Fast-twitch motor units are recruited as exercise intensity increases, thus increasing the reliance on carbohydrate as the predominant fuel source
During prolonged exercise at moderate- to high-intensity
- Carbohydrates contribute to almost 50% of total energy expenditure
- At the onset of exercise, the main form of carbohydrate utilised is muscle glycogen
During prolonged exercise, as duration/time increases…
- Muscle glycogen stores rapidly deplete by 40-60% within the first 90-120 mins
- Because of this, there is a compensatory increase in the reliance on blood glucose as the primary carbohydrate fuel source
Classic study that manipulated the diet of individuals over 3 days prior to undertaking a single bout of cycling exercise @ 70% VO2max to fatigue (Bergstrom et al. 1967)
Low CHO diet
- Lower than average pre-exercise muscle glycogen levels
- Able to cycle at workload for 60 mins before they fatigued
Classic study that manipulated the diet of individuals over 3 days prior to undertaking a single bout of cycling exercise @ 70% VO2max to fatigue (Bergstrom et al. 1967)
Same individuals were fed a normal CHO diet
- Normal pre-exercise muscle glycogen levels
- 2 fold higher level of muscle glycogen compared to low CHO diet
- Able to cycle for ~120 mins (60 mins long than low CHO diet) before fatigue occurred
Classic study that manipulated the diet of individuals over 3 days prior to undertaking a single bout of cycling exercise @ 70% VO2max to fatigue (Bergstrom et al. 1967)
On the final occasion, individuals were fed a high CHO diet
- Pre-exercise muscle glycogen content was 3-4 timed higher than low CHO diet measures
- Able to cycle for ~180 mins before fatigue
- Clearly shows the ergogenic effect of high pre-exercise muscle glycogen content on endurance exercise performance
Earlier studies
- Provided theoretical basis for dietary carbohydrate loading prior to exercise or “glycogen super compensation” as a strategy for athletes to enhance endurance exercise performance
- Highlight that starting exercise with low or inadequate muscle glycogen levels can have a detrimental effect on exercise performance
Endurance based sports (2+ hrs) and CHO demands
- Demands for adequate CHO as fuel often exceed the endogenous muscle glycogen storage capacity or the athlete’s ability to replenish muscle glycogen stores between events or bouts of intense exercise
Despite the success of “the legend of gatorade” commercial, it was not until the 1980s that researchers…
- Demonstrated that CHO feeding during prolonged exercise could improve exercise capacity during exercise lasting at least 2 hours or more, when muscle glycogen levels were significantly reduced
- This research explained how the ergogenic effect of ingesting CHO during exercise was achieved
Muscle glycogen breakdown during exercise primarily depends on…
Exercise intensity
CHO utilisation during low-intensity exercise
- Rate of CHO breakdown is slow
- Only a small reduction in muscle glycogen after ~120 mins
CHO utilisation during more intense or heavy exercise
- Rate of CHO breakdown is much greater
- Muscle glycogen content almost depleted after 60 mins
During heavy (60 mins) and moderate (120 mins) intensity exercise, fatigue occurs when muscle glycogen is depleted
- Because of the depleted glycogen, the muscle is not able to produce enough ATP rapidly enough the maintain exercise intensity
Under most exercise conditions, the rate of muscle glycogen breakdown is most rapid during the…
…early stages of exercise, when concentration or amount of glycogen in the muscle is at its highest
Muscle glycogen is broken down through a metabolic pathway called…
…glycogenolysis
The primary rate limiting enzyme that regulates this process is called…
…glycogen phosphorylase
Glycogen phosphorylase is controlled by…
…altering the proportion of the enzyme in the less active ‘b’ (i.e. beta) form and the more active ‘a’ (i.e. alpha) form
The transformation of phosphorylase ‘b’ to more active ‘a’ form occurs in response to…
…an increase in the localised levels of calcium that occur as a result of muscle contraction
Transformation to the more active ‘a’ form via phosphorylation also occurs in response to hormonal stimulation by…
…adrenaline
- Mediated via activation of beta-adrenergic receptors on the plasma membrane, which is followed by an increase in intracellular second messenger cyclic AMP (cAMP)
Glycogen phosphorylase is also controlled by…
…allosteric regulation
The activity of glycogen phosphorylase is increased through a rise in…
…the allosteric modulators; ADP, AMP, IMP and Pi
- These products of ATP use, occur in response to muscle contraction, and ensure the rate of muscle glycogenolysis is closely coupled to ATP demand
Another thing that can influence glycogen phosphorylase is the…
…glycogen concentration
- High levels of muscle glycogen increase the rate of glycogen breakdown in skeletal muscle
Why is muscle glycogen the preferred fuel source during exercise?
- Glycogenolysis is more energetically efficient (produces more ATP)
- Acts to modulate glucose uptake from the blood
- Helps to maintain blood glucose within normal levels in the absence of exogenous CHO intake (which is important under fasting conditions)
What regulates the increase in skeletal muscle glucose uptake during exercise
- 3 primary steps
1) Extracellular (outside the muscle)
- Factors that influence glucose supply to the muscle
- Incl. circulating glucose concentration in the blood/plasma, blood flow to contracting skeletal muscle
2) Membrane
- Factors that influence glucose transport across the plasma membrane or sarcolemma of the muscle
- Primarily regulated by the number or activity of glucose transporters (GLUT4)
3) Intracellular (inside the muscle)
- Factors that influence intracellular glucose metabolism or the processes within the muscle related to glucose utilisation or disposal (glycolysis and oxidative metabolism) or muscle glycogen breakdown (glycogenolysis)
Glucose supply = …
blood flow x blood glucose concentration
A physiological response to exercise is a marked increase in…
…blood flow
- The capillary networks supplying skeletal muscle
- Muscle blood flow can increase up to 20-fold during intense exercise
- More glucose is delivered to the working muscle to be taken up by the muscle
When muscle blood flow is well matched to the metabolic demands of the muscle, the other option available to increase glucose supply to the working muscle is by…
…changing the blood glucose concentration
Normal physiological range of blood glucose concentration
4-8mM
When blood glucose concentration is within normal range, the relationship between glucose concentration and muscle glucose uptake during exercise is…
…almost linear
- Indicates that an increase in glucose concentrations during exercise is proportional to an increase in glucose uptake by muscle
- e.g. ingesting glucose during exercise can increase or maintain blood glucose levels, resulting in an increase or maintenance in glucose supply or availability to the muscle.
During prolonged exercise, when blood glucose concentration decreases…
…muscle glucose supply and availability for glucose to be taken up by the muscle decreases as well
How does glucose get into a cell (esp. skeletal muscle cells)?
- A specialised transporter or protein is used that allows glucose entry across the cell membrane
The transport or glucose into cells occurs via…
…facilitated diffusion mediated by a family of glucose transporters, given the abbreviated GLUT, and a number to identify the particular transporter isoform
GLUT4
- The glucose transporter isoform, that is responsible for glucose transport in skeletal muscle
- Can also be found in adipose tissue and cardiac muscle
When stimulated, it translocates from a storage site inside the cell, to the cell surface (plasma membrane) where it facilitates the diffusion or uptake of glucose from the blood into the cell
When there is an increase in blood glucose levels in response to consuming a meal or feeding glucose…
…this stimulates the release of insulin from the pancreas
- An increase in the hormone insulin is a physiological feedback mechanism that acts to increase the translocation of GLUT4 to the muscle cell or plasma membrane which increases muscle glucose uptake, which lowers blood glucose levels