Review of Bioenergetics SP5005 Physiology Alex Nowicky power point slides: Powers and Howley- Exercise Physiology Ch 3 and 4 1

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 2

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 (O 2 ) (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) 4

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 5

Metabolism  Total of all chemical reactions that occur in the body – Anabolic reactions • Synthesis of molecules – Catabolic reactions • Breakdown of molecules  Bioenergetics- oxidation (O 2 ) – Converting foodstuffs (fats, proteins, carbohydrates) into energy 6

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 7

The Breakdown of Glucose: An Exergonic Reaction 8

Coupled Reactions 9

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 10

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 11

High-Energy Phosphates  Adenosine triphosphate (ATP) – Consists of adenine, ribose, and three linked phosphates  Formation

ADP + P i



ATP

 Breakdown

ATP

ATPase

ADP + P i + Energy

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Model of ATP as the Universal Energy Donor 13

Carbohydrate

w Readily available (if included in diet) and easily metabolized by muscles w Ingested, then taken up by muscles and liver and converted to glycogen w Glycogen stored in the liver is converted back to glucose as needed and transported by the blood to the muscles to form ATP 14

Fat (triglycerides)

w Provides substantial energy during prolonged, low intensity activity- light weight (little water in storage) w Body stores of fat are larger than carbohydrate reserves w Less accessible for metabolism because it must be reduced to glycerol and free fatty acids (FFA) w Only FFAs are used to form ATP- triglycerides- must be broken down by process of lipolysis 15

Protein -

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

w Can be used as energy source if converted to glucose via glucogenesis (or gluconeogenesis) w Can generate FFAs in times of starvation through lipogenesis w 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) 16

Oxidation of Fat- FFA via



- oxidation

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

w FFAs travel via blood to muscle fibers and are broken down by enzymes in the mitochondria into acetyl CoA. w Acetyl CoA enters the Krebs cycle and the electron transport chain.

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

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What Determines Oxidative Capacity?

w Oxidative enzyme activity within the muscle w Fiber-type composition and number of mitochondria w Endurance training w Oxygen availability and uptake in the lungs 18

Bioenergetics    Formation of ATP – Phosphocreatine (PC) breakdown – Degradation of glucose and glycogen (glycolysis) – Oxidative formation of ATP Anaerobic pathways – Do not involve O 2 – PC breakdown and glycolysis (lactate) Aerobic pathways- only occur in mitochondria – Electron transport system (ETS) -Requires O 2 – Oxidative phosphorylation 19

Anaerobic ATP Production  ATP-PC system – Immediate source of ATP

PC + ADP

Creatine kinase

ATP + C

 Glycolysis – Energy investment phase • Requires 2 ATP – Energy generation phase • Produces ATP, NADH (carrier molecule), and pyruvate or lactate 20

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 23

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)

NAD + 2H +



NADH + H +

 Flavin adenine dinucleotide (FAD)

FAD + 2H +



FADH 2

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Production of Lactic Acid   Normally, O 2 is available in the mitochondria to accept H + (and electrons) from NADH produced in glycolysis – In anaerobic pathways, O 2 is not available H + and electrons from NADH are accepted by pyruvic acid to form lactic acid 27

Conversion of Pyruvic Acid to Lactic Acid 28

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 O 2 form water to 29

3 Stages of Oxidative Phosphoryl ation 30

The Krebs Cycle 31

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) 32

Relationship Between the Metabolism of Proteins, Fats, and Carbohydrates 33

The Chemiosmotic Hypothesis of ATP Formation 34

Aerobic ATP yield from glucose

Metabolic Process High-Energy Products

Glycolysis 2 ATP 2 NADH Pyruvic acid to acetyl-CoA 2 NADH Krebs cycle 2 GTP 6 NADH 2 FADH

Grand Total ATP from Oxidative Phosphorylation ATP Subtotal

— 6 2 (if anaerobic) 8 (if aerobic) 6 — 18 4 14 16 34 38

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Summary- Oxidation of Carbohydrate

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.

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

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

w 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.

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

w 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)

w Energy in biological systems is measured in kilocalories.

w 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 distance Should be using SI units 1 Joule (J) = 1 N-m/s 2 1 kg-m = 1kg moved through 1 metre 1kcal = 426 kg-m = 4.186kiloJoules (kJ) 1 kJ = 0.2389 kcal ( 1kcal = 4.186kJ) 1 litre of O 2 consumed = 5.05kcal= 21.14 kJ (1ml of oxygen = .005kcal) - useful conversion factor 39

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/min 1MET = 3.5ml oxygen/kg/min= 0.0177kcal/kg/min 15 kcal/min= ? Oxygen/min (can you do this?) 40

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 Carbohydrates g kcal grams kcal

Liver glycogen Muscle glycogen Glucose in body fluids 110 250 15 451 1,025 62

Total 375 1,538 Fat

Subcutaneous Intramuscular 7,800 161 70,980 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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Oxygen consumption for Carbohydrate (glucose from glycogen) (C 6 H 12 0 6 )n + 6 O 2 --> 6 CO 2 +6 H 2 0 + 39 ATP 6 moles of O 2 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

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Aerobic ATP yield from FFA (free fatty acid - palmitic acid (16C) 16C  7 Acyl coA  7 acetyl coA

(C 16 H 32 0 2 ) + 23 O 2 --> 16 CO 2 +16 H 2 0 + 130 ATP 23 moles of O 2 needed to break down 1 of palmitic acid 23 moles x 22.4 l/mole oxygen = 512.2 l 512l/130 moles of ATP = 3.96 l O 2 /mole ATP ratio of carbon dioxide/oxygen = 16/23 = 0.7

15% more oxygen than metabolising glycogen, but

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advantage is light weight (little water) storage

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+P i – High levels of ATP inhibit ATP production – Low levels of ATP and high levels of ADP+P i stimulate ATP production Calcium may stimulate aerobic ATP production 46

Action of Rate-Limiting Enzymes 47

Control of Metabolic Pathways

Pathway

ATP-PC system

Rate-Limiting Enzyme

Creatine kinase

Stimulators

ADP

Inhibitors

ATP Glycolysis Phosphofructokinase AMP, ADP, P i ,  pH ATP, CP, citrate,  pH Krebs cycle Isocitrate dehydrogenase ADP, Ca Electron transport chain Cytochrome Oxidase ADP, P i ++ , NAD ATP, NADH ATP 48

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 49

Maximal capacity and power of three energy systems

System

phosphagen anaerobic glycolysis aerobic (from glycogen)

moles ATP/min power capacity

3.6

1.6

1.0

0.7

1.2

90.0

at rest - aerobic system supplies ATP with oxygen consumption about 0.3L/min, blood lactate remains constant 50

Contribution of energy systems 51

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 52

The Oxygen Deficit 53

Differences in VO 2 Between Trained and Untrained Subjects- Why?

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Recovery From Exercise: Metabolic Responses    Oxygen debt – Elevated VO 2 exercise for several minutes immediately following – Excess post-exercise oxygen consumption (EPOC) “Fast” portion of O 2 debt – Resynthesis of stored PC – Replacing muscle and blood O 2 stores “Slow” portion of O 2 debt – Elevated body temperature and catecholamines – Conversion of lactic acid to glucose (gluconeogenesis) 55

Oxygen Deficit and Debt During Light-Moderate and Heavy Exercise 56

Factors Contributing to EPOC 57

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 58

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 59

Metabolic Response to Exercise:

Incremental Exercise

  Oxygen uptake increases linearly until VO 2max is reached – No further increase in VO 2 work rate with increasing Physiological factors influencing VO 2max – Ability of cardiorespiratory system to deliver oxygen to muscles – Ability of muscles to take up the oxygen and produce ATP aerobically 60

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) – VCO 2 / VO 2 – Indicates fuel utilization • 0.70 = 100% fat • 0.85 = 50% fat, 50% CHO • 1.00 = 100% CHO  During steady state exercise – VCO 2 and VO 2 reflective of O 2 consumption and CO 2 production at the cellular level 62

Exercise Intensity and Fuel Selection    Low-intensity exercise (<30% VO 2max ) – Fats are primary fuel High-intensity exercise (>70% VO 2max ) – 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 63

Illustration of the “Crossover” Concept 64

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 65

Shift From CHO to Fat Metabolism During Prolonged Exercise 66

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 67

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 68

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 70

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 71