Energy metabolism during excersise

Question 1

What is the role of ATP in muscle contraction?

Answer 1

• ATP is the direct fuel for contraction, supplying the ATPase activity of myosin
• Therefore, ATP is needed to support muscle contraction, with ATP utilisation increasing more than 100-fold in milliseconds

Question 2

At rest muscle has approx. ___ mmol of ATP per kg wet weight

During vigorous contraction this lasts

In the short-term, muscle can increase its rate of production of ATP _____ fold

Answer 2

5

2

2-100

Question 3

How does muscle increase ATP production during excersise?

Answer 3

•Initially the main fuel for this is glycogen stored within the muscle itself; however as time goes on, other tissues need to co-operate to provide fuel for energy production

Question 4

How does Muscle metabolism work at rest (post-absorptive state)?

Answer 4

• In resting muscle, glycogen stores are maintained/replenished
• Oxidative metabolism of fatty acids provides energy for the muscle

Little lactate produced as pyruvate is used for glycogen synthesis or used in TCA cycle as sufficient oxygen present in the muscle

ATP not generated via PC system at rest

Question 5

What occurs in the muscle metabolism at the onset of excersise?

Answer 5

1. Glycogenolysis provides fuel source
2. Increase in O2 consumption for ox phos
3. Increased blood flow to muscles due to local mediators (NO) and β-adrenergic stimulation of vascular smooth muscles

Question 6

Amount of energy derived from glycolysis and ox phos is dependent on the _________ and _________ of the exercise

Answer 6

Amount of energy derived from glycolysis and ox phos is dependent on the intensity and duration of the exercise

Question 7

How is Mobilisation of muscle glycogen during exercise controlled?

Answer 7

Glycogen mobilization in the muscle is controlled by Ca2+ levels in the cytoplasm of muscle cells, levels of AMP and by adrenaline.

Question 8

How does Mobilisation of muscle glycogen during exercise occur?

Answer 8

Question 9

What is the role of Ca2+ in muscle contraction?

Answer 9

• Increase in Ca2+ concentration is the signal for muscle contraction
• Also increases muscle glycogen breakdown by activating glycogen phosphorylase to supply the energy required
• Stimulates the production of nitric oxide which causes vasodilation of the blood vessels and increased blood flow

Question 10

What are the Characteristics of Skeletal Muscle Blood Flow?

Answer 10

• Skeletal muscle accounts for about 20% of cardiac output at rest; can increase to more than 80% during extreme physical exertion.
• Coordinated, rhythmical contractions (e.g. running) enhance blood flow by means of the skeletal muscle pump mechanism.

Question 11

What is blood flow determined by?

Answer 11

• Blood flow is strongly determined by local regulatory (tissue and endothelial) factors such as tissue hypoxia, adenosine, K+, CO2, H+, and nitric oxide
• Vascular β2-adrenoceptors result in vasodilation when stimulated by agonists such as adrenaline

Question 12

How is metabolism hormonally controlled during excersise?

Answer 12

Question 13

What are the 3 systems for forming ATP in muscle?

Answer 13

Question 14

Complete the table on the 3 systems for forming ATP during excersise

Answer 14

Question 15

Which pathway has the highest energy?

Answer 15

Anaerobic energy pathways have a much higher power (rate of ATP production) but smaller capacity (total ATP produced) than aerobic pathways

In terms of aerobic metabolism, carbohydrate oxidation has a higher power output but a lower capacity than fat oxidation (discussed on Slide 23)

Question 16

What is Phosphocreatine (or creatine phosphate)?

Answer 16

PC: An extra source of energy in muscle cells

Question 17

What is the role of phosphocreatinine?

Answer 17

• First top-up source for muscle ATP
• At rest, muscle has about 100 mmol creatine phosphate (phosphocreatine) per kg dry weight. During vigorous contraction this lasts approx 16 secs
• May be enough for a 100-200 metre sprint

Question 18

What is the equation for phosphocreatinine?

Answer 18

Question 19

__________ and _______ are greatly stimulated during contraction

Answer 19

•Glycogen breakdown and glycolysis are greatly stimulated during contraction

Question 20

When does anaerobic glycolysis occur?

Answer 20

• If the increased rate of metabolism outstrips the oxygen supply, glycolysis can proceed anaerobically
• Much less ATP is produced and lactate builds up
• Even when the oxygen supply is sufficient, pyruvate may be formed faster than it can be oxidised. This also causes the accumulation of lactate

Question 21

What is the cori cycle?

Answer 21

Lactate is used by the liver to regenerate glucose which can be transferred back to the muscle for energy production. If there is insufficient blood flow through the muscle, lactic acid builds up in the muscle.

Question 22

When does aerobic metabolism occur during exersise?

Answer 22

• In addition to glycogen, muscle also uses fatty acids from the adipose tissue to maintain ATP levels.
• However, aerobic metabolism of glucose and fatty acid oxidation are dependent on an adequate oxygen supply to the muscle
• Oxygen is necessary for any ATP production via fatty acid oxidation

Question 23

What is fatigue?

Answer 23

• Inability to maintain desired power output
• Occurs when rate of ATP utilization exceeds its rate of synthesis

Question 24

How does fatigue occur?

Answer 24

• Accumulation of pyruvate and lactic acid in the contracting muscle result in a decline in force generated
• Due to decrease in muscle pH
• Glycolysis inhibited by H+ from lactic acid

Question 25

What proportion of metabolism do these take up at different distances?

Answer 25

Question 26

What is the effect of intensity and duration of exercise on method of ATP synthesis?

Answer 26

• Only 2 fuels are used in short sprints to replenish ATP, phosphocreatine and anaerobic glycogen breakdown to lactate
• As the distance increases, phosphocreatine levels are exhausted and the muscle relies solely on glycogen breakdown either anaerobically to lactate or aerobically to CO2 via the TCA cycle
• During the marathon, the muscles are reliant on oxidative metabolism of glycogen and also glucose from the liver and fatty acids from the adipose tissue

Question 27

Lable the type of metabolism

Answer 27

Question 28

How does muscle metabolism work during a sprint?

Answer 28

Fuel: PC & anaerobic glycolysis

• Catecholamines stimulate glycogen breakdown in muscle which is converted anaerobically to lactate. Phosphocreatine is converted to creatine with the transfer of Pi to ADP to form ATP
• Blood vessels are compressed during sprinting isolating the cells from the blood supply making the muscles reliant on anaerobic energy production from glycogen
• Large quantities of lactic acid produced as glycolysis proceeds which the liver can use to maintain blood glucose levels via gluconeogenesis

Question 29

How does muscle metabolism work during a middle distance run?

Answer 29

• As the distance increases aerobic oxidation of glycogen makes up 30% of the ATP required to support contraction. Some of the oxygen required may come from oxymyoglobin in the muscle
• Lactate is still a major end product of glycogen metabolism contributing 65% of the ATP required
• The contribution of phosphocreatine to the ATP required becomes less and less as the distance increases. At 800 metres it contributes 5% and essentially zero over 1500 metres

Question 30

How does muscle metabolism work during the first 10 minutes of a marathon?

Answer 30

•Muscle glycogen and glucose from the liver are used to power muscles, mainly through glycolysis. Increased vasodilation in the muscles increases O2 supply increasing the aerobic glycogen utilisation and ATP production.

Glycogen breakdown stimulated by increased AMP and adrenalin release

•Fatty acids are mobilised by the release of adrenalin to allow liver to maintain blood glucose levels by the provision of energy and the glycerol backbone

Question 31

How does muscle metabolism work 30 minutes - 2 hours into a marathon?

Answer 31

• ATP generated via oxidation of glucose and fatty acids. Increased reliance on fatty acid oxidation over this longer timespan of relatively intense exercise.
• Lactate, glycerol and muscle amino acids used to support glucose production by the liver, energy being derived from fatty acid oxidation.

Question 32

Oxidation of carbohydrate or fat in endurance exercise?

Answer 32

• Fats alone can supply most of the needs for resting muscle, but exercising muscle have an absolute requirement for some glucose
• Fatty acid breakdown during extended periods of exercise proceeds on a continual background level of glucose metabolism
• This requirement for a background level of glucose metabolism increases with exercise intensity

Question 33

What happens to muscle metabolism at 2+ hours in a marathon?

Answer 33

• About 90% of liver glycogen used. Insulin levels remain very low and glucagon levels elevated.
• Ketone bodies produced by the liver and may be used by muscle to generate ATP (in addition to fatty acids)

Question 34

What does hitting the wall mean?

Answer 34

•Hitting the wall means that exercise intensity drops because of a lack of available ATP

Question 35

What causes ‘hitting the wall’?

Answer 35

• A marathon requires about 700g of glycogen, whereas muscle and liver normally contain only 500g, therefore glycogen stores are largely depleted after 20 miles.
• Body switches to fatty acids as main source of energy with little glucose metabolism.
• Fatty acid oxidation only generates sufficient ATP for 50% of maximum power output and pace decreases as glycogen depleted – known as ‘hitting the wall’.

Question 36

Why is there a potential for hypoglycaemia in final stages of a marathon?

Answer 36

• With prolonged high-intensity exercise, liver glucose output may fall below muscle glucose uptake thus resulting in hypoglycaemia
• Typical symptoms of confusion, lack of cognitive function, lactic acidosis and exhaustion may occur (less likely with training)

Question 37

The Confused Marathon Runner

Jon entered the stadium for the final lap of his marathon race. He was well ahead of the pack. In the last minute or so, he seemed to become confused, his legs buckled and then he collapsed multiple times. What went wrong?

Answer 37

• In brief, Jon’s muscles consumed the fuels that were needed by his brain. Therefore there was not a sufficient supply of fuels to permit his brain cells to synthesize enough ATP for their needs.
• Muscle can use fatty acids or glucose for energy. High use of fatty acids requires their efficient delivery to muscle, and also efficient delivery of oxygen. If either is lacking glucose will be used.
• At the end of the race, Jon is pushing his resources to the limit. Excess use in muscle takes glucose from brain.
• A slight over demand on glucose can deplete blood and starve the brain of this energy source. Normally glycogen in liver will replace it, but at the end of the race, liver glycogen and muscle glycogen also are depleted.
• The brain can use glucose or ketoacids, but ketoacids are not available to the brain as Jon is not starved. The use of ketoacids by the brain requires a higher concentration of ketones in the blood than would be present after a marathon. Upregulation of the enzymes required to convert ketones into acetyl-CoA is also required; this takes around 3 days. Hence only glucose can fuel his brain.
• As a result Jon’s brain is starved of glucose and he suffers from confusion and collapses with exhaustion

Question 38

1. In the resting state briefly explain how skeletal muscle derives its energy?

Answer 38

Answer: From the aerobic oxidation of fatty acids via beta-oxidation with the acetyl CoA feeding into the TCA cycle and electron transport chain.

Question 39

2. Explain the mechanism by which the muscles cope with the increased demand for oxygen during a brisk walk / jog.

Answer 39

Answer: Vasodilation and increased blood supply to the muscles results from Ca2+-dependent nitric oxide production and β-adrenergic activation of the vascular smooth muscle.

Question 40

3. Briefly describe the metabolic changes that occur to sustain muscle contraction during a 100m sprint.

Answer 40

Answer: During sprinting phosphocreatine is used as a major substrate to generate ATP to support contraction

•catecholamines stimulate glycogen breakdown in muscle to provide 50% of the energy via glycolysis.

· With the intense muscle contraction blood vessels become compressed isolating the cells from the blood supply making the muscles reliant on anaerobic energy production with large quantities of lactic acid produced as the end product of glycolysis.

Question 41

After the first 10 minutes of a marathon run:

(i) What is the major fuel used to support contraction?
(ii) What is the metabolic end product of this process and how is it reutilized?

Answer 41

Answers: (i) Glycogen

(ii) Glycogen is converted to lactic acid via anaerobic glycolysis. The lactate is released into the bloodstream for transport to the liver for conversion into glucose via gluconeogenesis; this is then returned to the muscle completing the Cori cycle.

Question 42

5. Briefly describe in metabolic terms the process known as ‘hitting the wall’ after 20 miles of a marathon.

Answer 42

Answer: Muscle and liver glycogen are largely depleted after 20 miles.

•Body has to switch back to fatty acids as main source of energy,

(aerobic metabolism). This is not as efficient in terms of ATP

production while running.

•Lactate, glycerol and muscle amino acids are used to support

glucose production by the liver to prevent hypoglycaemia, energy being derived from fatty acid oxidation

Question 43

6. What two physiological mechanism(s) exist to ensure adequate oxygenation of the muscle during exercise?

Answer 43

Answer: The rise in Ca2+ at the onset of contraction results in the local release of nitric oxide which causes vasodilation.

•Adrenaline interacts with β-adrenergic receptors within the blood vessels causing relaxation and vasodilation.