Energy Systems and ATP Production

Work, Power, and Energy Expenditure

Energy is the capacity to do work.
Force is calculated by dividing work (Joules) by distance (meters).
Work is the product of force and the distance through which that force acts.
- Work (J) = Force (N) x distance (m)
The caloric equivalent of work is:
- 1 kcal = 4,184 Joules or 4.184 kJ
- 1 kilocalorie (kcal) = 1,000 calories
Power is how much work is accomplished per unit of time.
- Power (W) = work (J) / time (s)
Direct calorimetry measures heat production to indicate metabolic rate.
Indirect calorimetry measures oxygen consumption to estimate resting metabolic rate.
The relationship between speed and VO2 is linear.
Running economy refers to the oxygen cost for running at a specific speed.
- Lower VO2 at the same speed indicates better running economy.
MET (Metabolic Equivalent) represents the resting metabolic rate and is conventionally taken as 3.5 ml/kg/min.
- 3-6 METs = moderate intensity
- 6-10 METs = high intensity
- +10 METs = very high intensity

Bioenergetics

Major cell structures covered:
- Cell membrane (sarcolemma): A semipermeable membrane separating the cell from the extracellular environment.
- Nucleus: Contains genes that regulate protein synthesis.
- Cytoplasm: The fluid portion of the cell, containing organelles.
Endergonic reactions require energy to be added to the reactants (e.g., amino acids combining to make proteins).
Exergonic reactions release energy (e.g., breakdown of glucose).
A coupled reaction involves the liberation of energy in an exergonic reaction driving an endergonic reaction (e.g., oxidative-reduction reactions).
Oxidation is removing an electron, while reduction is the addition of an electron. Hydrogen atoms are often transferred in oxidation-reduction reactions.
Enzymes are catalysts that regulate the speed of reactions.
- Temperature and pH regulate enzyme activity.
- Enzymes have optimal temperatures and pH levels at which they are most active.
Enzymes lower the activation energy by impacting temperature and pH.
- They interact with specific substrates via a "lock and key model."
Most enzymes end with -ASE (e.g., Kinase, Dehydrogenase, oxidase, isomerases).
ATP (adenosine triphosphate) consists of adenine, ribose, and three linked phosphates.

ATP Production and Energy Systems

Fuels for ATP production include:
- Carbohydrates: Glycogen (stored in the muscle and liver), glucose (stored in adipose tissue as triglycerides).
- Fats: Fatty acids (skeletal muscle), triglycerides (fat in muscle and adipose tissue), phospholipids.
- Amino acids and lactate.
Protein is not a primary energy source during exercise; it only contributes during long-duration exercise or starvation when cellular proteins are broken down.
Three ATP synthesis pathways include:
- Glycolysis (anaerobic)
- Krebs Cycle (aerobic, occurs in the mitochondria)
- Cori Cycle (aerobic)
Other info regarding the 3 ATP sysnthesis pathways
- Creatine phosphate/ATP PC: Anerobic and located in the skeletal muscle
- Glycolysis (glucose) and glycogenolysis (glycogen): Anerobic and occurs in cytosol of muscle
- Oxidative metabolism is aerobic and takes place in the Mitochondria
An aerobic pathway uses oxygen, while an anaerobic pathway doesn't.
Oxidative phosphorylation has the greatest capacity for ATP synthesis.

Rate-Limiting Enzymes and Metabolic Processes

Phosphagen System (ATP-PCr System)
- Rate-limiting enzyme: Creatine Kinase
- Activators: High ADP levels (signals need for ATP production).
- Inhibitors: High ATP levels (signals sufficient energy availability).
Glycolysis
- Rate-limiting enzyme: Phosphofructokinase (PFK)
- Activators: AMP, ADP (signal low-energy state), Fructose-2,6-bisphosphate (enhances PFK activity in some tissues).
- Inhibitors: ATP (signals sufficient energy), Citrate (indicates high TCA cycle activity), Low pH (e.g., due to lactate accumulation)
Oxidative Phosphorylation (TCA Cycle & Electron Transport Chain)
- Rate-limiting enzyme: Isocitrate Dehydrogenase (TCA cycle)
- Activators: ADP (signals low energy availability), Ca2+ (stimulates ATP production in muscle), NAD+ (indicates a need for NADH regeneration).
- Inhibitors: ATP (signals sufficient energy), NADH (signals a reduced state, slowing down the cycle).
Major products of glycolysis: Pyruvate & Cytosol.
NADH and FADH play an important role in transfer of electrons which makes them electron carriers.
Lactate is formed under conditions with an excess amount of pyruvate produced.
- If there is no oxygen available to take hydrogens in mitochondria, then pyruvate accepts the hydrogens to form lactate.
- LDH (lactate dehydrogenase) catalyzes the formation

Oxidative Phosphorylation and Energy Yield

Oxidative phosphorylation involves glycolysis (producing 2 pyruvic acids), the citric acid cycle (pyruvic acids are converted to acetyl-CoA), the citric acid cycle, and finally the ETC where oxygen is the final electron acceptor.
The Krebs cycle produces 3 NADH and 1 FADH2 molecules, in addition to one GTP.
- The electron transport chain removes electrons from NADH and FADH, producing ATP (2.5 per NADH/1.5 per FADH).
- Hydrogen from NADH and FADH in ETC are accepted by O2 and form water.
2.5 ATP can be produced from the electrons donated by NADH, starting in complex 1.
1.5 ATP can be produced from the electrons donated by FADH, starting in complex 2.
The chemiosmotic hypothesis of ATP formation states that as electrons are transferred along the cytochrome chain, released energy is used to "pump" hydrogens from NADH and FADH from inside the mitochondria across the inner mitochondrial membrane.
- Accumulation between the inside and outside mitochondrial membrane occurs through 3 pumps.
Two key variables of exercise influence the relative contribution of the three ATP producing pathways: duration and intensity. All three systems are active at any given time.

Energy Requirements and Metabolic Responses

At rest:
- Almost 100% of ATP is produced by aerobic metabolism.
- Blood lactate levels are low (<1.0 mmol/L).
- Resting O2 consumption is 0.25 L/min, which is 3.5 ml/kg/min = 1 MET.
When transitioning from rest to exercise:
- ATP production increases immediately.
- The body goes from rest (oxidative phosphorylation) to initial (phosphagen/glycolysis) to long duration (oxidative phosphorylation).
- Oxygen uptake increases rapidly, achieving a steady state within 1-4 minutes.
- The ATP requirement is met through aerobic ATP production, with initial ATP production through anaerobic pathways (ATP-PC system and glycolysis).
- Oxygen deficit, lag in oxygen uptake at the beginning of exercise
Oxygen deficit is associated with the start of exercise, is the amount of time it takes for a person to reach steady-state VO2.
ATP-PC system and anaerobic glycolysis are the sources of ATP during the oxygen deficit
Training reduces the oxygen deficit.
EPOC (Excess Post-exercise Oxygen Consumption) involves rapid and slow portions.
- Rapid: resynthesis of stored PC and replenishing muscle and blood O2 stores.
- Slow: elevated heart rate (= increased energy need) and elevated body temperature (= increased metabolic rate).
- Elevated epinephrine and norepinephrine = increase metabolic rat
- Conversion of lactate to glucose (gluconeogenesis)

Intensity, Lactate Removal, and Metabolic Responses

Greater intensity or duration of exercise means greater EPOC.
Lactate is removed more rapidly from the blood if light exercise is performed during recovery (optimal intensity 30-40% VO2 max).
- Lactate goes to the liver, converted to glucose or converted to pyruvate.
Response for short term, intense exercise
- First 1-5 sec
- ATP produced by ATP-PC system
  - <10 sec relies on ATP-Pc
- Intense exercise >5 sec
  - shift ATP production by glycolysis
- 45 sec
  - AT production by ATP-PC, glycolysis, and aerobic systems
  - 70% anaerobic/30% aerobic at 60 sec
  - 50% anaerobic/50% aerobic at 2 min
Response for prolonged exercise
10 min
- steady-state oxygen uptake maintained during submaximal exercise (below lactate threshold)
- hot/humid environment or high intensity
- upwards drift in oxygen uptake due to increase in body temp and blood levels of epinephrine and norepinephrine
Exercising in a hot-humid environment impacts oxygen update
Maximal oxygen uptake (VO2max) is the physiological ceiling for delivery of O2 to muscle
Lactate threshold:
- The point at which blood lactate acid rises systematically during incremental exercise.
- Low muscle oxygen (hypoxia)
- Accelerated glycolysis
- Recruitment of fast-twitch muscle fibers
- Reduced rate of lactate removal from the blood

Lactate Threshold, Fuel Selection

Lactate threshold is used in sports for prediction of performance, planning training programs, as a training intensity marker, and for training HR based on LT.
Lactate does not cause muscle soreness.
- Lactate removal is rapid following exercise
- If it did, power athletes would be sore every after every workout
- Microscopic injury to muscle fibers lead to inflammation
RER (respiratory exchange ratio) is VCO2/VO2.
- An RER of 0.7 illustrates that our usage of fat is 100%.
- An RER of 1.0 means we utilize 100% carbohydrates.
Increased exercise intensity: Fats are the primary fuel source for prolonged low intensity. During high intensity exercise carbohydrates are the primary fuel
"Crossover" concept: Shift from fat to CHO metabolism as exercise intensity increases.
Low intensity exercise is better for burning fat.
Increased exercise duration increases the percentage of fat burning while carbohydrate metabolism decreases.
Sources of carbohydrate during exercise include muscle glycogen.
- Primary source during high-intensity
- Supplies carbs in first hour of exercise
Blood glucose
- From liver glycogenesis.
- Primary source during low-intensity
- Important during long-duration exercise
Our sources of fat during exercise are:
- Intramuscular triglycerides
- Primary source during high-intensity
Plasma FFA
- Adipose tissue lipolysis
- FFA converted to acetyl-CoA and enters citric acid cycle
- Primary source during low-intensity
- More important during the decline of muscle triglyceride levels in long-duration

Protein's Role and the Cori Cycle

Protein plays a minor role in energy production during exercise (2% contribution). This may increase 5-10% late in prolonged-duration exercise.
- Broken down into amino acids where the liver can convert alanine to glucose or the muscle directly metabolize branch chain amino acids and alanine
- Enzymes that degrade proteins are activated in long-term exercise
The Cori Cycle: Lactate produced by skeletal muscle is transported to the liver, where the liver converts lactate to glucose, and then glucose is transported back to muscle to be used as a fuel.