WEEK 4: Exercise Metabolism 101: How Do We Fuel Physical Activity?

What do muscle signaling and contraction rely on?

Muscle signaling relies on sodium (Na⁺) and potassium (K⁺). Sodium and potassium movement requires the Na⁺/K⁺ ATPase, which uses ATP. Continuous signaling from the brain allows action potentials to reach the neuromuscular junction.

What is the neuromuscular junction (NMJ)?

The connection between the nervous system and muscle.

What is acetylcholine (ACh), and what does it do?

Acetylcholine (ACh) is the main signal that tells muscles to contract. This leads to actin and myosin interaction and muscle contraction.

What is the role of T-tubules in muscle fibres?

Extensions of the outside of the cell that invaginate into the centre of the muscle fibre. Allow signals to travel throughout the muscle fibre. Allow the muscle to contract simultaneously. Allow glucose uptake through GLUT4.

How does a signal travel from the neuromuscular junction to the sarcoplasmic reticulum?

A signal travels along the nerves to the neuromuscular junction, which releases a neurotransmitter – acetylcholine. This creates a signal that affects the sarcolemma and travels down the T-tubules and causes a release of Ca2+ from the sarcoplasmic reticulum.

What is the role of calcium in muscle contraction?

Muscle signaling causes calcium release. Calcium contributes to muscle contraction and GLUT4 signaling and glucose uptake. Ca2+ binds to troponin, which causes the tropomyosin to change configuration, which then exposes the myosin binding site on actin. This allows the power stroke to occur.

How does the power stroke occur during muscle contraction?

A contraction occurs with energy obtained from the hydrolysis or use of ATP bound to myosin, which is then released as ADP + Pi. ATP is broken down. Cleavage of its phosphate releases energy that allows the power stroke.

Why is ATP required after the power stroke?

The re-binding of ATP relaxes the myofibril, releasing myosin. ATP turnover is required to release the power stroke and allow the cycle to continue. ATP must continually turn over to maintain contraction.

How does the muscle reset after contraction?

The reuptake of Ca2+ then resets the tropomyosin-troponin complex (also uses ATP), blocking the myosin binding site on actin. A contraction will only proceed if Ca2+ is then available to bind to troponin again and occurs via a signal from the neuromuscular junction.

What processes require ATP during muscle contraction?

1. Power stroke
2. Power stroke release
3. Calcium reuptake into the sarcoplasmic reticulum
4. Nerve signaling through sodium and potassium movement

Why does ATP demand increase during exercise?

Higher-intensity exercise requires more ATP.    More vigorous contraction increases ATP demand.    Intramuscular fuel is limited.    This helps explain why glycogen only lasts for a certain amount of time.

What is the key takeaway about the muscle contraction cycle?

Muscle contraction does not end with the power stroke.    It ends with the release/resetting process.

How does the body produce ATP?

The body produces ATP on demand.    Chemical energy is stored in macronutrients: carbohydrates, fat and protein.    Energy is released in small amounts when needed by a controlled set of enzymatic reactions as needed.

Why doesn't the body store large amounts of ATP?

ATP is bulky and energetically expensive to make.    It is volatile, so the body does not store large amounts.

Why is ATP produced on demand?

Helps ensure energy is used efficiently.    Some energy is lost as heat during energy production.    The goal is to maximize the amount of energy transferred into ATP rather than lost as heat.

Where is chemical energy stored, and how is it transferred to bodily processes?

In the three macronutrients: carbohydrates, fat and protein.    No. The body does not transfer energy directly from food to bodily processes.    Energy is transferred through ATP.

Do B vitamins directly provide energy?

No. B vitamins do not directly provide energy.    They help the body harness energy.    Iron and B vitamins support energy-production processes.

What are the two immediate ATP sources in muscle?

5. Free ATP
6. Phosphocreatine (creatine phosphate)

What are the characteristics of free ATP stored in muscle?

A small amount is stored in muscle.    Does not require oxygen.    Barely enough to get activity started.

What is phosphocreatine, and how does it regenerate ATP?

Stored in muscle.    4 to 6x greater than ATP.    Provides quick energy for a few seconds.    Not enough to sustain most athletic activities.    ATP loses a phosphate group and becomes ADP.    Phosphocreatine donates its phosphate to ADP.    ADP becomes ATP again.    This allows rapid ATP regeneration.

What is total creatine?

Total creatine = creatine + phosphocreatine.

What is the purpose of creatine supplementation?

Increases total creatine levels.    Can increase phosphocreatine levels.    Provides more quick energy.    Particularly important for short-term, high-performance activities.

Where is creatine found in food, and how do levels differ between vegetarians and omnivores?

Typically found in meat.    Vegetarians tend to have lower creatine levels than omnivores.

What are the four intramuscular fuel sources?

ATP.    Phosphocreatine.    Intramuscular triglycerides.    Glycogen.

What are intramuscular triglycerides?

Fat stored inside the muscle cell.    Different from subcutaneous fat, which is stored outside the cells.

Why are intramuscular fuel sources limited?

Intramuscular triglycerides and glycogen have limited storage capacity.    The body must also rely on extramuscular fuel sources.

What are the extramuscular fuel sources?

Triglycerides from adipose tissue.    Fatty acids in the blood.    Glycogen from the liver.    Glucose from the bloodstream.    Exogenous fuel from food and drinks.    Carbon skeletons from amino acids.

How do amino acids contribute to energy production?

Amino acid carbon skeletons can contribute to energy production.    They can primarily be used in the TCA cycle.    Some can enter the bloodstream and be converted into glucose, which can return to the muscle.

What is the role of capillaries in muscle energy supply?

Capillaries deliver oxygen and fuel to the muscle.    Muscle cannot store everything it needs.    Extramuscular fuel must be transported to the muscle.

Can LDL and VLDL contribute triglycerides to muscle?

Yes. Triglycerides from LDL and VLDL can contribute.    However, they contribute very little.

What are the two important glycogen stores in the body?

Muscle glycogen.    Liver glycogen.

What is the difference between muscle glycogen and liver glycogen?

Muscle glycogen supports muscle activity.    Primarily supports muscle contraction and movement.    Used directly by the muscle during exercise.    Liver glycogen maintains normal blood glucose levels.    Supplies glucose to the bloodstream.    Helps ensure blood sugar remains stable during exercise.

What happens to liver glycogen and blood glucose during exercise?

When glucose is removed from the blood, blood sugar can decrease.    The liver contributes glucose to maintain blood sugar.    This helps prevent dizziness and supports concentration.    During exercise, both muscle and liver glycogen are used.

Why can liver glycogen be substantially reduced by morning?

Liver glycogen can decrease substantially overnight.    The body continues using energy while sleeping.    The brain and other tissues continue requiring fuel.    Because we are not eating, the liver provides glucose.    This can result in significantly reduced liver glycogen by morning.

Why should liver glycogen be considered when fueling morning exercise?

Liver glycogen levels should also be considered when fueling morning exercise.

How can carbohydrate drinks help support fuel availability during exercise?

Providing glucose through drinks such as Gatorade or Powerade can support fuel availability.    This can help spare both muscle and liver glycogen.

What happens to fuel utilization as exercise intensity increases?

Carbohydrate becomes increasingly important as intensity increases.    Higher intensity increases reliance on glycolysis.    Oxygen becomes limiting.    Anaerobic processes become more important.    Glycogen use increases.    Plasma glucose utilization increases.

At what exercise intensity is muscle triglyceride use highest?

Muscle triglyceride use is highest at moderate intensity.

Why does intramuscular fuel become more important at higher exercise intensities?

Higher-intensity exercise requires energy more quickly.    Blood flow, oxygen delivery and transport become limiting factors.    The body relies more on fuel already stored within the muscle.

What is the key takeaway about fuel use during higher-intensity exercise?

Higher-intensity exercise increases reliance on carbohydrate and intramuscular fuel.

What do metabolic processes produce, and what do electron carriers do?

ATP.    NADH.    FADH2.    (electron carriers)    Carry energy from metabolic processes.    Deliver electrons to the electron transport chain.    Allow ATP production.    The ATP generated can be used immediately for energy, but NADH and FADH2 must be further processed to make ATP.    This further processing is done in the mitochondria of the cell.

What is the purpose of the TCA cycle in relation to electron carriers?

One of the purposes of the TCA cycle is to produce NADH and FADH₂.    These electron carriers enter the electron transport chain.    The electron transport chain produces ATP.

Which B vitamins support the production of NADH and FADH₂?

Niacin is used for NADH production.    Riboflavin is used for FADH₂ production.    Adequate B vitamins are important for energy production.

How much ATP do NADH and FADH₂ produce according to the lecture?

NADH: 3 ATP.    FADH₂: 2 ATP.

What are the two main carbohydrate sources used for energy?

Muscle glycogen.    Blood glucose, which can come from liver glycogen or exogenous glucose.

What happens to glucose during anaerobic glycolysis?

Glucose is broken down through glycolysis.    Produces approximately 2–3 ATP.    Pyruvate is predominantly converted into lactate under anaerobic conditions.

What happens during aerobic metabolism of glucose?

Glycolysis produces pyruvate.    Pyruvate enters the TCA cycle.    Can produce approximately 36–38 ATP.

What is glycogenolysis, and where is glycogen stored within muscle cells?

Breakdown of glycogen.    Glycogen is stored in granules within muscle cells.    Granules are located near glycolytic mechanisms.    This allows glycogen to be broken down quickly.

How is glycogen structured within its granules, and why are its branches important?

Glycogen granules resemble a tennis ball with many branches.    Mathematical modelling suggests approximately 13–14 layers.    The many branches provide multiple ends from which glucose can be removed.    Multiple glucose molecules can be cleaved simultaneously.    Glycogen is not broken down one glucose molecule at a time.

What is glycogen phosphorylase, and what regulates it?

The limiting enzyme for glycogenolysis.    Energy state of the cell.    Adrenaline (epinephrine).

How does adrenaline affect glycogen phosphorylase?

Adrenaline increases its activity through phosphorylation.    Multiple glycogen phosphorylase enzymes are present on each granule.    This allows glycogen to be broken down quickly.

What are the steps of glycogenolysis?

7. Glycogen phosphorylase removes glucose from glycogen.
8. Produces glucose-1-phosphate (G1P).
9. The phosphate moves from carbon 1 to carbon 6.
10. Produces glucose-6-phosphate (G6P).
11. G6P enters glycolysis.
12. Glycolysis produces pyruvate.

What are the possible fates of glucose in muscle?

It can be stored.     It can be oxidized for energy.

Can glucose leave muscle as glucose after entering the muscle cell?

No. Glucose that enters muscle cannot leave again as glucose.     Muscle does not have glucose-6-phosphatase.     Therefore, it cannot remove the phosphate from G6P to release free glucose.

What are the possible fates of glucose in the liver, and why can the liver release it into the bloodstream?

It can be oxidized.     It can be stored.     It can be broken down.     It can be released into the bloodstream as glucose.     The liver contains glucose-6-phosphatase.     This enzyme removes the phosphate from G6P.     This produces glucose that can enter the bloodstream.     The glucose can then be used by other tissues.

What is the difference between muscle and liver glucose release?

Muscle does not have glucose-6-phosphatase and cannot release glucose as glucose.     The liver has glucose-6-phosphatase and can release glucose into the bloodstream.

What is glycolysis, and where can glucose enter it from?

Glycolysis breaks down glucose to produce pyruvate.     Blood glucose.     Muscle glycogen.

Why does ATP yield during glycolysis depend on the source of glucose?

Blood glucose must first be phosphorylated to become G6P.     This requires 1 ATP.     Glucose from muscle glycogen is already at G6P, so this ATP does not need to be invested during glycolysis.

What happens during glycolysis when it starts with blood glucose?

13. Blood glucose enters the cell.
14. It must be phosphorylated to become G6P.
15. This requires 1 ATP.
16. Another ATP is used at the major rate-limiting step.
17. The six-carbon glucose molecule is split into two three-carbon molecules.
18. Each three-carbon molecule produces 2 ATP.
19. Total ATP produced = 4 ATP.
20. Two ATP were invested.

What is the net ATP yield from blood glucose during glycolysis?

2 ATP

What happens during glycolysis when it starts with muscle glycogen?

21. Glycogen breakdown produces G1P.
22. G1P is converted into G6P.
23. G6P enters glycolysis.
24. The phosphate was already provided during glycogen breakdown.
25. One ATP is used at the rate-limiting step.
26. The glucose molecule is split into two three-carbon molecules.
27. Each produces 2 ATP.
28. Total ATP produced = 4 ATP.
29. One ATP was invested.

What is the net ATP yield from muscle glycogen during glycolysis?

3 ATP

What is the major rate-limiting enzyme of glycolysis, and what regulates it?

Phosphofructokinase (PFK).     The energy state of the cell.     ATP levels.     NADH levels.

What happens to glucose during glycolysis in terms of carbon molecules, and how much ATP is produced?

The six-carbon glucose molecule is split into two three-carbon molecules.     Each three-carbon molecule produces 2 ATP.     Total ATP produced = 4 AT

What are the two possible fates of pyruvate?

Anaerobic conditions: predominantly converted into lactate.     Aerobic conditions: enters the TCA cycle.

What happens to NADH during lactate production?

Glycolysis produces NADH.     Under aerobic conditions, NADH has the potential to be shuttled into the mitochondria to produce ATP.     Under anaerobic conditions, NADH is consumed when pyruvate is converted into lactate.     Therefore, that NADH cannot be used to produce its potential 3 ATP.

Why is glycogen important for athletes?

Glycolysis only produces 2–3 ATP per glucose molecule.     Muscle glycogen storage is limited.     Blood glucose availability is also limited.     Higher-intensity exercise burns through glycogen quickly.     Therefore, athletes need to maintain high glycogen levels.     The lecturer emphasizes the importance of maximizing glycogen availability for most athletes.

How much ATP is invested and produced from blood glucose and muscle glycogen during glycolysis?

Blood glucose:     ATP invested: 2.     ATP produced: 4.     Net ATP: 2.

Muscle glycogen: ATP invested: 1. ATP produced: 4. Net ATP: 3.

What is the Cori cycle, and what are its steps?

Lactate is not wasted. It can be transported to the liver and converted back into glucose. Glucose can return to the muscle for energy. Glucose can also help maintain blood glucose levels.

1. During anaerobic glycolysis, pyruvate is converted into lactate.
2. Lactate (a three-carbon molecule) enters the bloodstream.
3. Lactate travels to the liver.
4. The liver uses lactate to produce glucose.
5. The glucose is released into the bloodstream.
6. The muscle can take up the glucose and use it again.

Why is lactate not considered waste?

Lactate is often associated with muscle acidity, changes in pH and fatigue.    However, lactate is valuable because it can be used to produce more glucose.    Lactate is recycled through the Cori cycle.    Lactate is a valuable fuel source that can be recycled into glucose rather than simply being treated as waste.

What is our capacity to break down glycogen and glucose?

We have a tremendous capacity to break down glycogen and glucose.    We have other sources of glucose available, which are important for high-intensity exercise.    Most athletes work at moderate or intense exercise intensities.

Can glucose be broken down under aerobic and anaerobic conditions?

Glucose can be broken down under both anaerobic and aerobic conditions.    Under anaerobic conditions, glucose produces only about 2–3 ATP per glucose.

Why does anaerobic glucose metabolism use up glycogen quickly?

The 2–3 ATP produced per glucose is not a large amount.    This means glycogen is used up relatively quickly.    The blood can only supply a limited amount of glucose.

What metabolic shift occurs as exercise intensity changes?

There is a shift between using glucose and fat.    The shift is related to what is happening metabolically in the body.

What happens to pyruvate under anaerobic conditions?

Under anaerobic conditions, pyruvate is more likely to be converted into lactate.    Lactate can still be used by the body.    Hydrogen ions are associated with changes in pH.

What is the role of pyruvate dehydrogenase (PDH)?

Pyruvate dehydrogenase is the first step before the TCA cycle.    It is not technically part of the TCA cycle, but it is an important step.    It is a complex rather than just one enzyme.

What is required for pyruvate dehydrogenase to function?

The process involves approximately five or six B vitamins.

What happens during a dehydrogenase reaction?

Hydrogen is removed from a molecule.    The hydrogen is typically added to an electron carrier.    In this step, NAD is used to form NADH.

How much ATP can the NADH from PDH produce?

Each NADH has the capacity to produce 3 ATP, based on the ATP values used in the lecture.    There are two pyruvate molecules produced from one glucose molecule.

What are decarboxylations, and how many carbon dioxide molecules are produced from one pyruvate?

Decarboxylations involve removing carbon from a molecule.    Carbon dioxide is produced during these reactions.    One carbon dioxide is produced during the pyruvate dehydrogenase step.    Two additional carbon dioxide molecules are produced during the TCA cycle.    This produces three carbon dioxide molecules per pyruvate.

What happens during the PDH step?

A three-carbon pyruvate molecule loses one carbon as carbon dioxide.    The remaining two-carbon molecule becomes acetyl-CoA.

Why is acetyl-CoA important in energy metabolism?

Acetyl-CoA enters the TCA cycle.    It is an important point where carbohydrate and fat metabolism meet.    Fat metabolism also produces acetyl-CoA.    The amount of acetyl-CoA available helps regulate the balance between glucose and fat use.

What happens when acetyl-CoA enters the TCA cycle?

The two-carbon acetyl-CoA combines with four-carbon oxaloacetate.    This produces citrate.    The cycle continues from there.

What is oxaloacetate, and why is it important in the TCA cycle?

Oxaloacetate is a four-carbon substrate that combines with two-carbon acetyl-CoA.    Together, they form citrate.    Oxaloacetate is a limiting substrate in the TCA cycle.    It can slow down the cycle if there is not enough available.    Acetyl-CoA can enter the cycle easily, but oxaloacetate can become limiting.

What happens during the TCA cycle?

The cycle involves decarboxylations and dehydrogenation reactions.    Carbon dioxide is produced.    Electron carriers are produced.

What does one pyruvate produce during the TCA cycle?

Three NADH are produced during the TCA cycle.    Each NADH has a capacity to produce 3 ATP, based on the lecture's ATP values.    One FADH2 is also produced.    One ATP is produced using energy from GTP.

How is ATP produced using GTP during the TCA cycle?

The TCA cycle produces GTP.    The energy from GTP is used to make ATP.    Technically, one ATP is produced, but GTP is used in the process.

Where does the TCA cycle occur, and how is it connected to the electron transport chain?

The TCA cycle occurs in the mitochondria.    The process moves from the cytosol into the mitochondria.    One of the steps in the TCA cycle is also one of the complexes of the electron transport chain.    The two processes are connected near or on the mitochondrial membrane.

What is anaplerosis, and how does protein support the TCA cycle?

Anaplerosis is the process of using amino acids and protein to feed the TCA cycle.    It helps maintain the substrates needed for the cycle to continue.    Amino acids can feed into different points of the TCA cycle.    The muscle contains a small free amino acid pool.    Amino acids from this pool can help maintain the cycle.

Do amino acids have to come entirely from outside the muscle?

No.    The muscle also has the capacity to make some amino acids from other amino acids.

What is the main role of protein in energy metabolism?

Protein primarily supports energy metabolism by helping feed the TCA cycle.    This allows the cycle to continue and produce the ATP needed.

Do all three macronutrients contribute to energy production?

Yes.    Protein, fat, and carbohydrates all support energy and power.    Exercise intensity primarily determines the balance between fat and carbohydrate use.    Protein contribution is more related to fuel availability in the muscle than exercise intensity.

Where is the electron transport chain located, and what is the structure of the mitochondria?

The electron transport chain is located on the inner mitochondrial membrane.    The mitochondria have a double membrane.    The outer membrane faces the cytosol and is relatively permeable to most substances.    The inner mitochondrial membrane controls what moves through i    The inner membrane has folds, creating more surface area.

What do NADH and FADH2 do in the electron transport chain?

NADH and FADH2 provide electrons.    The electrons are passed through the different complexes of the electron transport chain.

What role does iron play in the electron transport chain?

Iron is an important cofactor.    It can accept electrons and then release them.

What happens to hydrogen ions during the electron transport chain?

Hydrogen ions are moved from the mitochondrial matrix into the space between the inner and outer mitochondrial membranes.

What does the movement of hydrogen ions create?

It creates an electrochemical gradient.    Positive charge builds up in the space between the membranes.    This creates an imbalance across the inner mitochondrial membrane.

Why do hydrogen ions move back into the mitochondrial matrix?

The positive charge in the inner mitochondrial space creates a gradient.    Hydrogen ions move back toward the matrix through ATPase.

What is the role of ATPase during oxidative phosphorylation?

ATPase is a complex protein and enzyme.    It combines ADP and inorganic phosphate (Pi) to produce ATP.    The movement of hydrogen ions through ATPase helps drive ATP production.    Approximately four hydrogen ions are needed to produce one ATP.

What are the end products of oxidative phosphorylation?

TP is produced.    Metabolic water is produced.    The molecules undergo full oxidation.