1 Review of Bioenergetics SP5005 Physiology Alex Nowicky power point slides: Powers and Howley-...

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Review of Bioenergetics

SP5005 Physiology

Alex Nowicky

power point slides: Powers and Howley- Exercise Physiology Ch 3 and 4

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What is bioenergetics?

Study of energy in living systems what it is? Where does it come from? How is it measured? How is it produced and used by human body at

rest and during exercise? Part of science of biochemistry -studies

conversion of matter into energy by living systems

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For your own study use any ex physiology text and cover the following: Energy sources recovery from exercise measurement of energy, work and

power

This lecture is an overview of these!

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Aim: review energy metabolism

Learning outcomes ATP is central to all energy transactions Oxidation (O2) (in mitochondria) central define aerobic and anaerobic pathways -

systems of enzymes and their regulation fate of fuels - CHO, fats and proteins-

relative yields of useful energy (ATP)

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Learning outcomes (con’t)

role of glycogenolysyis, -oxidation, gluconeogenesis

indirect calorimetry for monitoring energy expenditure- oxygen consumption- (RER)

contribution of fuel supply during exercise (short vs. long duration)

role aerobic and anaerobic systems during exercise and recovery

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Metabolism

Total of all chemical reactions that occur in the body– Anabolic reactions

• Synthesis of molecules

– Catabolic reactions• Breakdown of molecules

Bioenergetics- oxidation (O2)

– Converting foodstuffs (fats, proteins, carbohydrates) into energy

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Cellular Chemical Reactions

Endergonic reactions– Require energy to be added

Exergonic reactions– Release energy

Coupled reactions– Liberation of energy in an exergonic

reaction drives an endergonic reaction

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The Breakdown of Glucose: An Exergonic Reaction

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Coupled Reactions

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Enzymes

Catalysts that regulate the speed of reactions– Lower the energy of activation

Factors that regulate enzyme activity– Temperature (what happens with changes in

T?)– pH ( what happens with changes in pH?)

Interact with specific substrates– Lock and key model

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Fuels for Exercise

Carbohydrates – Glucose

• Stored as glycogen in liver and muscle

Fats– Primarily fatty acids

• Stored as triglycerides- adipose tissue and muscles

Proteins– Not a primary energy source during exercise

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High-Energy Phosphates

Adenosine triphosphate (ATP)– Consists of adenine, ribose, and three

linked phosphates Formation

Breakdown

ADP + Pi ATP

ADP + Pi + EnergyATP ATPase

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Model of ATP as the Universal Energy Donor

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Carbohydrate

Readily available (if included in diet) and easily metabolized by muscles

Ingested, then taken up by muscles and liver and converted to glycogen

Glycogen stored in the liver is converted back to glucose as needed and transported by the blood to the muscles to form ATP

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Fat (triglycerides)

Provides substantial energy during prolonged, low-intensity activity- light weight (little water in storage)

Body stores of fat are larger than carbohydrate reserves

Less accessible for metabolism because it must be reduced to glycerol and free fatty acids (FFA)

Only FFAs are used to form ATP- triglycerides- must be broken down by process of lipolysis

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Protein - Body uses little protein during rest and exercise (less than 5% to 10%).

Can be used as energy source if converted to glucose via glucogenesis (or gluconeogenesis)

Can generate FFAs in times of starvation through lipogenesis

Only basic units of protein—amino acids—can be used for energy- via transamination feed into Kreb’s cycle

• waste produce is ammonia - must be excreted (as urea)

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Oxidation of Fat- FFA via - oxidation

Lypolysis—breakdown of triglycerides into glycerol and free fatty acids (FFAs).

FFAs travel via blood to muscle fibers and are broken down by enzymes in the mitochondria into acetyl CoA.

Acetyl CoA enters the Krebs cycle and the electron transport chain.

Fat oxidation requires more oxygen and generates more energy than carbohydrate oxidation.

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What Determines Oxidative Capacity?

Oxidative enzyme activity within the muscle

Fiber-type composition and number of mitochondria

Endurance training

Oxygen availability and uptake in the lungs

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Bioenergetics

Formation of ATP – Phosphocreatine (PC) breakdown

– Degradation of glucose and glycogen (glycolysis)

– Oxidative formation of ATP Anaerobic pathways

– Do not involve O2

– PC breakdown and glycolysis (lactate) Aerobic pathways- only occur in mitochondria

– Electron transport system (ETS) -Requires O2

– Oxidative phosphorylation

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Anaerobic ATP Production

ATP-PC system– Immediate source of ATP

Glycolysis– Energy investment phase

• Requires 2 ATP

– Energy generation phase• Produces ATP, NADH (carrier molecule), and

pyruvate or lactate

PC + ADP ATP + CCreatine kinase

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RECREATING ATP WITH PCr

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ATP AND PCr DURING SPRINTING

What does this show?

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The Two Phases of Glycolysis

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Glycolysis: Energy Investment Phase

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Glycolysis: Energy Generation Phase

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Oxidation-Reduction Reactions

Oxidation– Molecule accepts electrons (along with H+)

Reduction– Molecule donates electrons

Nicotinomide adenine dinucleotide (NAD)

Flavin adenine dinucleotide (FAD)

FAD + 2H+ FADH2

NAD + 2H+ NADH + H+

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Production of Lactic Acid

Normally, O2 is available in the mitochondria to accept H+ (and electrons) from NADH produced in glycolysis– In anaerobic pathways, O2 is not available

H+ and electrons from NADH are accepted by pyruvic acid to form lactic acid

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Conversion of Pyruvic Acid to Lactic Acid

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Aerobic ATP Production

Krebs cycle (citric acid cycle)– Completes the oxidation of substrates and

produces NADH and FADH to enter the electron transport chain

Electron transport chain – Electrons removed from NADH and FADH are

passed along a series of carriers to produce ATP

– H+ from NADH and FADH are accepted by O2 to form water

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3 Stages of Oxidative Phosphoryl-ation

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The Krebs Cycle

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Glycogen Breakdown and Synthesis

Glycolysis—Breakdown of glucose; may be anaerobic or aerobic

Glycogenesis—Process by which glycogen is synthesized from glucose to be stored in the liver

Glycogenolysis—Process by which glycogen is broken into glucose-1-phosphate to be used by muscles

Gluco(neo)genesis- formation of glucose from lipids and proteins via intermediates (lactate, pyruvate, amino acids)

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Relationship Between the Metabolism of Proteins, Fats, and Carbohydrates

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The Chemiosmotic Hypothesis of ATP Formation

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Metabolic Process High-EnergyProducts

ATP from OxidativePhosphorylation

ATP Subtotal

Glycolysis 2 ATP2 NADH

—6

2 (if anaerobic)8 (if aerobic)

Pyruvic acid to acetyl-CoA 2 NADH 6 14

Krebs cycle 2 GTP6 NADH2 FADH

—184

163438

Grand Total 38

Aerobic ATP yield from glucose

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1. Pyruvic acid from glycolysis is converted to acetyl coenzyme A (acetyl CoA).

2. Acetyl CoA enters the Krebs cycle and forms 2 ATP, carbon dioxide, and hydrogen.

3. Hydrogen in the cell combines with two coenzymes that carry it to the electron transport chain.

Summary- Oxidation of Carbohydrate

4. Electron transport chain recombines hydrogen atoms to produce ATP and water.

5. One molecule of glycogen can generate up to 39 molecules of ATP.

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Summary (con’t) - Oxidation of Fat

Lypolysis—breakdown of triglycerides into glycerol and free fatty acids (FFAs).

FFAs travel via blood to muscle fibers and are broken down by enzymes in the mitochondria into acetic acid which is converted to acetyl CoA.

Acetyl CoA enters the Krebs cycle and the electron transport chain.

Fat oxidation requires more oxygen and generates more energy than carbohydrate oxidation.

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Stop for 10 min break

Any questions?

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Kilocalorie and other units (SI)

Energy in biological systems is measured in kilocalories.

1 kilocalorie is the amount of heat energy needed to raise 1 kg of water 1°C at 15 °C. 1kcal= 1000cal

Work - energy - application of force through a distanceShould be using SI units1 Joule (J) = 1 N-m/s2

1 kg-m = 1kg moved through 1 metre1kcal = 426 kg-m = 4.186kiloJoules (kJ)

1 kJ = 0.2389 kcal ( 1kcal = 4.186kJ)1 litre of O2 consumed = 5.05kcal= 21.14 kJ (1ml of oxygen = .005kcal) - useful conversion factor

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Power to perform uses up energy- how much oxygen consumption to supply energy?

Power - work/time (Watts or hp)

1hp = 745 watts= 10.7kcal/min

1L of oxygen/min consumption= 5.05kcal/min= 21 kJ/min1MET = 3.5ml oxygen/kg/min= 0.0177kcal/kg/min

15 kcal/min= ? Oxygen/min (can you do this?)

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CARBOHYDRATE vs FAT

1 gram of CHO--> 4 kcal

1 gram of FFA (palmitic acid)--> 9 kcal

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Body Stores of Fuels and Energy

g kcal

Carbohydrates grams kcal

Liver glycogen 110 451

Muscle glycogen 250 1,025

Glucose in body fluids 15 62

Total 375 1,538Fat

Subcutaneous 7,800 70,980

Intramuscular 161 1,465

Total 7,961 72,445

Note. These estimates are based on an average body weight of 65 kg (143 lb) with 12% body fat.

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(C6H1206)n + 6 O2 --> 6 CO2 +6 H20 + 39 ATP

6 moles of O2 needed to break down 1 mole of glycogen

6 moles x 22.4 l/mole oxygen = 134.4 l

134.4l/39 moles of ATP = 3.45 l/mole ATP

at rest takes about 10-15 min,during max exercise takes about 1 min

ratio (RQ) carbon dioxide/oxygen = 6/6 = 1

Oxygen consumption for Carbohydrate (glucose from glycogen)

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Aerobic ATP yield from FFA (free fatty acid - palmitic acid (16C)

16C 7 Acyl coA 7 acetyl coA

(C16H3202) + 23 O2 --> 16 CO2 +16 H20 + 130 ATP

23 moles of O2 needed to break down 1 of palmitic acid23 moles x 22.4 l/mole oxygen = 512.2 l

512l/130 moles of ATP = 3.96 l O2/mole ATP

ratio of carbon dioxide/oxygen = 16/23 = 0.7

15% more oxygen than metabolising glycogen, but advantage is light weight (little water) storage

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How do we determine efficiency of ox phos- respiration (metabolism of glucose)? Efficiency =

38moles ATP x 7.3kcal/mole ATP

686 kcal/mole glucose

= 0.4 x100% = 40% (60% lost heat)

how does this compare to mechanical engine?

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Control of Bioenergetics

Rate-limiting enzymes– An enzyme that regulates the rate of a metabolic

pathway

Levels of ATP and ADP+Pi

– High levels of ATP inhibit ATP production

– Low levels of ATP and high levels of ADP+Pi stimulate ATP production

Calcium may stimulate aerobic ATP production

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Action of Rate-Limiting Enzymes

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Control of Metabolic Pathways

Pathway Rate-LimitingEnzyme

Stimulators Inhibitors

ATP-PC system Creatine kinase ADP ATP

Glycolysis Phosphofructokinase AMP, ADP, Pi, pH ATP, CP, citrate, pH

Krebs cycle Isocitratedehydrogenase

ADP, Ca++, NAD ATP, NADH

Electron transportchain

Cytochrome Oxidase ADP, Pi ATP

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Interaction Between Aerobic and Anaerobic ATP Production

Energy to perform exercise comes from an interaction between aerobic and anaerobic pathways

Effect of duration and intensity– Short-term, high-intensity activities

• Greater contribution of anaerobic energy systems

– Long-term, low to moderate-intensity exercise• Majority of ATP produced from aerobic sources

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Maximal capacity and power of three energy systems

System moles ATP/min power capacity

phosphagen 3.6 0.7

anaerobic glycolysis 1.6 1.2

aerobic (from glycogen) 1.0 90.0

at rest - aerobic system supplies ATP with oxygen consumption about 0.3L/min, blood lactate remains constant

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Contribution of energy systems

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Rest-to-Exercise Transitions

Oxygen uptake increases rapidly– Reaches steady state within 1-4 minutes

Oxygen deficit– Lag in oxygen uptake at the beginning of

exercise– Suggests anaerobic pathways contribute to

total ATP production After steady state is reached, ATP

requirement is met through aerobic ATP production

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The Oxygen Deficit

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Differences in VO2 Between Trained and Untrained Subjects- Why?

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Recovery From Exercise: Metabolic Responses

Oxygen debt– Elevated VO2 for several minutes immediately following

exercise– Excess post-exercise oxygen consumption (EPOC)

“Fast” portion of O2 debt– Resynthesis of stored PC– Replacing muscle and blood O2 stores

“Slow” portion of O2 debt– Elevated body temperature and catecholamines– Conversion of lactic acid to glucose (gluconeogenesis)

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Oxygen Deficit and Debt During Light-Moderate and Heavy Exercise

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Factors Contributing to EPOC

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Metabolic Response to Exercise: Short-Term Intense Exercise

High-intensity, short-term exercise (2-20 seconds)– ATP production through ATP-PC system

Intense exercise longer than 20 seconds– ATP production via anaerobic glycolysis

High-intensity exercise longer than 45 seconds– ATP production through ATP-PC, glycolysis,

and aerobic systems

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Metabolic Response to Exercise: Prolonged Exercise Exercise longer than 10 minutes

– ATP production primarily from aerobic metabolism

– Steady state oxygen uptake can generally be maintained

Prolonged exercise in a hot/humid environment or at high intensity– Steady state not achieved– Upward drift in oxygen uptake over time

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Metabolic Response to Exercise: Incremental Exercise Oxygen uptake increases linearly until

VO2max is reached– No further increase in VO2 with increasing

work rate Physiological factors influencing VO2max

– Ability of cardiorespiratory system to deliver oxygen to muscles

– Ability of muscles to take up the oxygen and produce ATP aerobically

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Changes in Oxygen Uptake With Incremental Exercise- explain?

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Estimation of Fuel Utilization During Exercise- from overall equations

Respiratory exchange ratio (RER or R)– VCO2 / VO2

– Indicates fuel utilization • 0.70 = 100% fat• 0.85 = 50% fat, 50% CHO• 1.00 = 100% CHO

During steady state exercise– VCO2 and VO2 reflective of O2 consumption

and CO2 production at the cellular level

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Exercise Intensity and Fuel Selection Low-intensity exercise (<30% VO2max)

– Fats are primary fuel High-intensity exercise (>70% VO2max)

– CHO are primary fuel “Crossover” concept

– Describes the shift from fat to CHO metabolism as exercise intensity increases

– Due to:• Recruitment of fast muscle fibers• Increasing blood levels of epinephrine

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Illustration of the “Crossover” Concept

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Exercise Duration and Fuel Selection During prolonged exercise there is a

shift from CHO metabolism toward fat metabolism

Increased rate of lipolysis– Breakdown of triglycerides into glycerol

and free fatty acids (FFA)– Stimulated by rising blood levels of

epinephrine

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Shift From CHO to Fat Metabolism During Prolonged Exercise

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Interaction of Fat and CHO Metabolism During Exercise “Fats burn in the flame of carbohydrates” Glycogen is depleted during prolonged

high-intensity exercise– Reduced rate of glycolysis and production of

pyruvate– Reduced Krebs cycle intermediates– Reduced fat oxidation

• Fats are metabolized by Krebs cycle

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Sources of Fuel During Exercise

Carbohydrate– Blood glucose– Muscle glycogen

Fat– Plasma FFA (from adipose tissue lipolysis)– Intramuscular triglycerides

Protein– Only a small contribution to total energy production (only ~2%)

• May increase to 5-15% late in prolonged exercise

Blood lactate– Gluconeogenesis in liver

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Effect of Exercise Intensity on Muscle Fuel Source

What does this graph show?

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Effect of Exercise Duration on Muscle Fuel Source- summarise

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Summary

Aerobic and anaerobic systems What regulates metabolic pathways? What is the RER? Describe how fuel utilisation is affected by

intensity and duration of exercise What happens during recovery from exercise? A note about ATP yield- some sources say 38

some say 36 with aerobic resp