BPK 312 Lecture 3 - SFU.ca - Simon Fraser Universitymwhite1/BPK 312 Lecture 3.pdfBPK 312 Nutrition...

BPK 312 Nutrition for Fitness & Sport

Lecture 3 Nutrient Roles in Bioenergetics

1.  Learning Objectives for Lecture 3

2.  Bioenergetics/Conservation of Energy

3.  Redox Reactions

4.  ATP/Phosphocreatine

5.  Cellular Oxidation/Electron Transport/Oxidative Phosphorylation

6.  Energy Release from Macronutrients

7.  The Metabolic Mill 1

1. Lecture 3 Learning Objectives (LO3) LO3-1: Define bioenergetics and give a description of the nutrition-energy interaction, energy transfer from macronutrients and cellular respiration.

LO3-2: Define and explain oxidation-reduction reactions as well as how they are important in energy transfer from macronutrients to ATP.

LO3-3: Explain how phosphocreatine and high energy phosphate bonds allow short term, explosive activity.

LO3-4: Explain the details of how electron transport in the respiratory chain and oxidative phosphorylation allow the transfer of energy from macronutrients to ATP.

LO3-5: Explain and describe the steps of energy transfer from: (i) glycogen and glucose to ATP in glycolysis, (ii) from coenzymes to high energy phosphate bonds in the citric acid cycle and (iii) from lactate to glycogen in the Cori Cycle

LO3-6: Name the sources of fat for catabolism and describe the steps in transfer of energy from triacylglycerols in beta-oxidation to the electron transport chain for ATP production.

LO3-7:Explain deamination, transamination and how the carbon ‘skeletons’ from amino acids are catabolized to give gluconeogenic as well as ketogenic intermediates for energy transfer.

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2. Bioenergetics & Conservation of Energy §  Bioenergetics refers to flow of energy within a living

system.

§  Aerobic chemical reactions do & anaerobic chemical reactions do not require oxygen.

§  Energy is transferred from the sun to plants by photosynthesis using chlorophyll, H2O & CO2 to produce carbohydrates (CHO) including glucose. Overall equation for photosynthesis:

§  Cellular respiration in animals allows recovery of food chemical energy stored in plants

§  Herbivores, carnivores and omnivores transfer energy transfer from different food sources

§  Image Source: https://en.wikipedia.org/w/index.php?title=Photosynthesis&oldid=759051544 3

Energy and Laws of Thermodynamics §  First law – Energy is neither created nor destroyed, but instead,

transforms from one state to another without being used up.

§  There are six forms of interchangeable energy states: •  Chemical, Light, Electric, Mechanical, Heat, Nuclear

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2. Bioenergetics & Conservation of Energy

Biologic Work

§  Takes one of three forms:

•  Mechanical work of muscle contraction

•  Chemical work for synthesizing molecules

•  Transport work that concentrates diverse substances in body fluids

‘On engraisse pas les cochons à l'eau claire’ Jeanne Beauregard, né Archambault, Calixa-Lavallée, Qc, 1908-1985

Recall Potential Energy and Kinetic Energy §  Potential energy (PE) refers

to energy associated with a substance’s structure or position.

§  Kinetic Energy (KE) refers to energy of motion.

§  PE and KE constitute the total energy of any system.

§  Releasing PE transforms it into KE of motion.

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2. Bioenergetics & Conservation of Energy

Energy transformation in the human body depend on:

•  (i) Oxidation-reduction (redox) reactions & (ii) Chemical reactions that conserve & liberate energy in Adenosine Triphosphate (ATP)

3. Redox Reactions §  Oxidation–reduction reactions couple: •  Oxidation = a substance loses H+, electrons or oxygen giving a ↑valence •  Reduction = a substance gains electrons giving a ↓valence §  Redox reactions power the body’s energy transfer processes.

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Fig 4-5: Example of a redox reaction during intense exercise - the reduction of pyruvate to give lactate & subsequent oxidation of lactate to give pyruvate during recovery cf slide 22

LIG

HT

MO

DE

RAT

E

STR

EN

UO

US

MA

XIM

AL

LDH LDH

(Lactate Dehydrogenase = LDH)

7 Fig 4-8: Adenosine Triphosphate (ATP), the body’s energy currency that powers all biological work

4. Adenosine Triphosphate (ATP) & Phosphocreatine (PCr) •  ATP is the body’s

primary energy carrier molecule that captures free energy in high energy phosphate bonds

•  Splits rapidly without O2

•  Only 80-100 g of ATP stored in body ∴ there is a continual resynthesis of ATP

Examples of work carried out in the body using ATP

2 outermost phosphate bonds are ‘high energy’ phosphate bonds.

Tissue Synthesis

Digestion

Muscle Contraction

Nerve Conduction

Circulation

Glandular

4. Adenosine Triphosphate (ATP) & Phosphocreatine (PCr) §  Potential energy (PE) is extracted

from macronutrients in food & conserved within phosphate bonds within ATP.

§  Chemical PE in ATP powers all biologic work.

• Adenosine TriPhosphatase (ATPase) for ATP degradation & energy release

•  for rapid anaerobic energy supply

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Fig 4-7: Simplified ATP image

ATP + H2O → ADP + Pi + 7.3 kcal/mol ATPase

ADP + Pi → ATP ATP Synthase

• ATP Synthesis

Phosphocreatine (PCr): The Energy Reservoir

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Fig 4-9: ATP & PCr sources of anaerobic phosphate bond energy. Energy released from splitting PCr helps resynthesize ATP from ADP & Pi; Adenosine triphosphatase (ATPase)

§ In addition to ATP, PCr is another high-energy phosphate compound.

§ PCr quickly releases large amounts of energy when bonds between creatine & phosphate are broken.

§ Cells store 4–6 x more PCr than ATP

§ Is a reservoir of high-energy phosphate bonds, for short-term 8-10 s explosive, all out muscular exercise

§ Phosphorylation gives energy transfer in phosphate bonds

4. Adenosine Triphosphate (ATP) & Phosphocreatine (PCr)

Creatine Phosphokinase

ATPase

10 Fig 4-6: Burning glucose in a fire vs. cellular oxidation of glucose

5. Cellular Oxidation, Electron Transport Chain (ETC) & Oxidative Phosphorylation

CELLULAR OXIDATON OF GLUCOSE BURNING OF GLUCOSE

ACTIVATION ENERGY ACTIVATION ENERGY

sudden release of all chemical

energy

slow step-wise release of

chemical energy


§  Most energy for ATP phosphorylation is from oxidation of hydrogen (H) from macronutrients, CHO, lipids & protein

§  Constitutes the mechanism for aerobic energy metabolism

§  Involves the transfer of hydrogen atoms & electrons •  Loss of hydrogen= oxidation & gain of hydrogen=reduction

•  Highly specific dehydrogenase co-enzymes are reduced with H from macronutrients

•  Nicotinamide Adenine Dinucleotide (NAD+) from niacin (Vit B3)

•  Flavin Adenine Dinucleotide (FAD) from riboflavin (Vit B2)

•  NADH & FADH2 are 2 high energy molecules carrying H & their electrons

§  Mitochondria contain cytochrome carrier molecules on their inner membrane that remove electrons from H & pass them to O2

§  Electron transport by cytochromes is the ‘respiratory chain’

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Chemical Reactions in Mitochondria Animation Button nb change ‘create to ‘transfer’ of energy in this animation

http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-03-mitochondria/mitochondria.html

Oxidative Phosphorylation

§  Refers to energy transfer through phosphate bonds

§  Oxidative phosphorylation synthesizes ATP by transferring H & electrons from NADH and FADH2 to oxygen.

§  >90% of body’s ATP synthesis

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Fig 4-10: Schematic diagram for oxidation of hydrogen from NADH & FADH2 for subsequent electron transport for the reduction of O2.


Electron Transport & Oxidative Phosphorylation

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Fig 4-11: In the body chemical energy is liberated with each of 3 hydrogen/electron pairs from NADH & FADH2 are shuttled by 5 mitochondrial cytochromes; cytochromes are Fe containing proteins. This energy is conserved in ATP in high energy phosphate bonds.


1

2

3

Cytochrome 2 e-

Cytochrome 2e-

Cytochrome 2e-

Cytochrome 2e-

Cytochrome 2e-

Electron Transport Animation

Button

http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-15-electron_transport/electron_transport.html

Electron Transport Chain (ETC) & Oxidative Phosphorylation

•  Theoretical value for aerobic ATP production from oxidation of H & subsequent phosphorylation is: NADH + H+ + 3 ADP + 3 Pi + ½ O2 → NAD+ + H2O + 3 ATP

•  ATP needs to be transported out of the mitochondria at the cost of some ATP

•  On average the net yield is 2.5 ATP synthesized per NADH, when FADH2 donates H this gives on average a net yield of 1.5 ATP synthesized from each hydrogen pair

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5. Cellular Oxidation, Electron Transport & Oxidative Phosphorylation

Efficiency of Electron Transport Chain (ETC) & Oxidative Phosphorylation

•  Formation of each mole of ATP conserves ~ 7 kcal of energy

•  Since 2.5 moles ATP is produced per mole of NADH then 2.5 x 7 kcal = ~18 kcal is conserved as chemical energy

•  The relative efficiency is ~34% for transferring chemical energy by ETC-oxidative phosphorylation since 1 mole of NADH liberates 52 kcal, i.e. ~18 kcal/52 kcal x 100 = ~34%.

•  Remaining 66% of this energy is dissipated as heat

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Role of Oxygen in Energy Metabolism •  3 conditions for ATP re-synthesis using energy from macronutrients

–  Cond. 1: Availability of reduced NADH & FADH2 in tissues

–  Cond. 2: Presence of oxidizing agent O2 in the tissues

–  Cond. 3: Sufficient concentration of the enzymes & mitochondria in the tissues to ensure energy transfer reactions proceed at their appropriate rate

•  Oxygen is the final electron acceptor in the respiratory chain & combines with hydrogen to form water.

•  Strenuous Exercise

–  In Cond. 2 if there is inadequate O2 in the tissues or in Cond 3 if the rate of delivery of O2 is inadequate these give an imbalance between H release & acceptance by O2, i.e. its reduction.

–  Electron flow down ETC backs up, H accumulates & lactate forms as give in Fig 4-15 on a following slide in this lecture. 16


6. Energy Release from Macronutrients

Sources for ATP formation include:

i.  Glucose derived from liver glycogen

ii.  Triacylglycerol & glycogen molecules stored within skeletal muscle cells/fibers

iii.  Free fatty acids (FFA) derived from triacylglycerol in liver and adipocytes that enter the bloodstream for delivery to active muscle

iv.  Intramuscular & liver-derived carbon skeletons of amino acids 17

Fig 4-12

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•  Liver produces rich sources of amino acids (aa) & glucose (glycogen) •  Adipocytes give large amounts of free fatty acids (FFA) •  These compounds are released into blood & are carried to skeletal m. •  Most energy transfer takes place in mitochondria within skeletal m. •  Intramuscular energy sources include ATP, PCr, Triacylglycerol (TAG),

glycogen & carbon skeletons from aa’s


Fig 4-13: Macronutrient Fuel Sources

Intramuscular Energy Stores

FFA

Glucose

Deaminated aa

Glucose

Glycogen

Mitochondrion

Citric Acid Cycle

aa

TAG

FFA

ATP

Energy Release from Carbohydrates

§  1° function of CHO is to supply energy for cellular work.

§  in a bomb calorimeter the complete breakdown of 1 mol of glucose of 180 g liberates 686 kcal of energy

•  Synthesis of 1 mol ATP needs 7.3 kcal of energy

•  All energy in glucose oxidation could give 94 mol of ATP

•  In muscle phosphate bonds conserve only 34%, i.e. 34% of 686 kcal/mol = 233 kcal/mol of energy in ATP bonds with the remainder dissipated as heat.

•  ∴ 1 mol of glucose breakdown gives 233 kcal/7.3 kcal x mol-1 = 32 mol of ATP

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C6H12O6 + 6 O2 → 6CO2 + 6H2O - 686 kcal/mol


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6. Energy Release from Macronutrients Glucose Degradation

Occurs in two stages:

1.  Anaerobic: Glucose breaks down relatively rapidly to 2 molecules of pyruvate in the reactions of glycolysis

2.  Aerobic: Pyruvate degrades further to carbon dioxide and water in the reactions of the citric acid cycle

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§  In cytosol & anaerobic cond. §  Glycolysis gives 5-10% of

total ATP from a glucose molecule

§  Substrate-level phosphorylation in glycolysis gives net gain of 2 ATP

§  Hydrogen release in glycolysis gives 2 NADH

§  for max exercise <90 s

§  Glycogenolysis gives net gain 3 ATP b/c 1st step bypassed

§  Lactate formation

Fig 4-13 6. Energy Release from Macronutrients

Glycogen phosphorylase

1.  Hexokinase

2.  Glucose 6-Phosphate isomerase

3. Phosphofructo-kinase

4. Aldolase

5. Triosephosphate isomerase

6. Glyceraldehyde 3- phosphate

dehydrogenase

7. Phosphoglycerate kinase

8.Phosphoglyceromutase

9. Enolase

10. Pyruvate kinase

ENZYMES 1 1

2

3 4

6

7

8

9

10

5

Glycolysis http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-02-glycolysis/

glycolysis.html

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•  In heavy exercise when energy demand exceeds O2 supply, ETC can’t process all NADH

•  Depends on reaction 6 in glycolysis & for NAD+ availability to oxidize ‘3-phosphoglyceraldehyde’

•  dramatically slows glycolytic rate & ↑ lactic acid production results

•  Lactate is a valuable source of chemical energy in the Cori Cycle

•  nb at physiological pH, lactic acid dissociates to lactate & H+

Fig 4-15: Lactic Acid Formation when excess H+ from NADH temporarily combines with pyruvate. This frees NAD+ to accept more H+ from glycolysis, cf slide 6

Lactate Dehydrogenase = LDH

6. Energy Release from Macronutrients Lactate Formation & Use

Cori Cycle

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•  Lactate is a valuable source of chemical energy during exercise

1.  Lactic acid from skeletal muscle enters venous circulation & dissociates to lactate & H+

2.  Lactate enters liver where it is converted to pyruvate & then via gluconeogenesis, there is a resynthesis of glucose.

3.  Blood glucose as well as muscle & liver glycogen can subsequently be maintained.

4.  Glucose is released from liver to arterial blood to active skeletal muscle.

Fig 4-16

1

23

4

Cori Cycle Animation

Button

Glucose

http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-25-cori_cycle/cori_cycle.html

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Citric Acid Cycle (CAC) §  2nd stage of CHO breakdown is

the CAC.

§  Irreversible joining of pyruvate with CoA, a Vit. B derivative, from Vit B6 or pantothenic acid, to acetyl-CoA

§  This releases 2 H atoms to reduce both NAD+ & FAD

6. Energy Release from Macronutrients Fig 4-18

§ The acetyl portion of acetyl-CoA joins with oxaloacetate to form citrate from citric acid.

§ Each acetyl-CoA gives 2 CO2 & 4 pairs of hydrogen atoms, plus 1 high energy Guanosine-5'-triphosphate (GTP)

e.g. Pyruvate + NAD+ + CoA → acetyl-CoA + CO2 + NADH + H+

citrate

Citric Acid Cycle

Animation Button

isocitrate

oxaloacetate

α-ketoglutarate Succinyl-CoA

Succinate

malate

oxalosuccinate

fumarate

http://download.lww.com/wolterskluwer_vitalstream_

com/animation_library/HP-16-citric_acid/

citric_acid_cycle.html

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Fig 4-17- Schematic Diagram of hydrogen formation & subsequent oxidation during aerobic energy metabolism.


Phase 1: CAC generates H atoms during breakdown of acetyl CoA

Phase 2: ATP is reformed when these H’s are oxidized via aerobic electron transport -oxidative phosphorylation

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Fig 4-19: Net Yield of 32 ATP molecules during complete oxidation of 1 glucose molecule through glycolysis, the CAC & electron transport chain

Energy Release from Fat – Lipolysis §  Stored fat represents the body’s biggest source of PE.

§  Energy sources for fat catabolism include:

i. Triacylglycerol stored directly in skeletal m. fiber

ii. Circulating triacylglycerol (TAG) in lipoprotein complexes

iii. Circulating free fatty acids

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TAG + 3 H2O → glycerol + 3 fatty acids

3 steps in lipoysis, steps 1&2 with HSL, Step 3 with HSL & monoglyceride lipase

Hormone Sensitive Lipase

3,5 cyclic monophosphate (cAMP)

•  cAMP Activation: stimulated by epinephrine, norepinephrine (e.g. exercise), glucagon, growth hormone + inhibited by lactate, insulin & ketones

•  these circulating factors don’t enter cell but activate cAMP & Hormone Sensitive Lipase

Lipolysis Animation

http://

download.lww.com/wolterskluwer_vitalstr

eam_com/animation_library/

HP-26-triacylglycerol/triacylglycerol.html

Adipocytes

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6. Energy Release from Macronutrients Fig 4-20: Fat storage & mobilization or lipolysis

§  TAG fat droplets take up to 95% of adipocyte volume & is major FFA source

§  Lipase stimulates glycerol & FFA release from adipocytes

§  FFA bind to albumin in the plasma

§  Long chain fatty acids enter muscle fibers by diffusion or by protein mediated transport &:

Fat Mobilzation Animation

Lipase http://

download.lww.com/wolterskluwer_vitalstre

am_com/animation_library/

HP-17-fat_mobilization/fat_mobilization.html

(i) form muscle intracellular TAG (ii) bind to CoA & then to carnitine by actions of carnitine-acyl-CoA transferase I & II fatty acids enter mitochondria (iii) Carnitine + fatty acyl-CoA à acylcarnitine + CoA (iv) end product is Acetyl-CoA à CAC & ETC to give ATP (iv) ↑[Acetyl-CoA]/[CoA] ratio ↓FA transfer to mitoch. §  Short & medium chain FA diffuse freely into mitochon., cf Lec #7, slides 3-5

Breakdown of Glycerol and Fatty Acids §  Glycerol

•  Provides carbon skeletons for glucose synthesis, enters glycolytic pathway as 3-phosphoglyceraldehyde to give ATP by substrate-level phosphorylation

§  Fatty acids

•  Beta (ß)-oxidation for fatty acid oxidation converts a free fatty acid to multiple acetyl-CoA molecules.

•  H+ released during fatty acid catabolism is oxidized through the respiratory chain.

•  Note CAC rate depends on concentration of its intermediates, including oxaloacetate & malate, that are derived from CHO.

•  A low CHO diet can limit fatty acid oxidation, due a slow rate of the citric acid cycle.

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C15H32O2 + 23 O2 → 16CO2 + 16H2O + 2397 kcal

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6. Energy Release from Macronutrients Breakdown of Glycerol and Fatty Acid Fragments

Fig 4-21: General scheme of glycerol & fatty acid fragment breakdown

Electron transport chain accepts pairs of hydrogen from glycolysis, citric acid cycle and ß-oxidation

*** Fat burns in a carbohydrate flame***

Energy Release from Protein

§  Protein plays a role as an energy substrate during endurance activities and heavy trainings.

§  Deamination: Nitrogen is removed from the amino acid by the liver

§  Transamination: when an amino group is passed to another compound

§  remaining carbon skeletons enter metabolic pathways to produce ATP.

§  especially evident for the branched chained amino acids leucine, isoleucine, valine, glutamine & aspartate

§  Excessive intake of protein is converted to body fat.

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A. Alanine Structure B. Transamination •  The nitrogen

containing amine group is transferred to other compounds

•  Allows availability of the carbon skeleton to enter into energy metabolism

•  e.g. the compound enters into the citric acid cycle

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Fig. 1-16 A: Chemical structure of aa alanine B: Transamination

Transamination

Animation

Glutamate Pyruvate

α-ketoglutaric acid Alanine

Glutamine transaminase

http://download.lww.com/wolterskluwer_vitalstream_com/

animation_library/HP-23-transamination/transamination.html

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Fig 4-21: Glucogenic and ketogenic amino acids.

•  Carbon skeletons of amino acids that form pyruvate or directly enter the citric acid cycle are glucogenic because they can form glucose

•  Carbon skeletons of amino acids that form acetyl-CoA are ketogenic because they can’t form glucose molecules but rather synthesize fat

Glucogenic & Ketogenic Amino Acids

Fig. 1-20: Glucose-Alanine Cycle 34


Gluconeogenesis

Deamination

•  In prolonged exercise this cycle accounts for 10-15% of total exercise energy requirement

•  after 4 h of continuous light exercise alanine-derived glucose accounts for 45% of the livers total glucose release

Glucose–Alanine Cycle Animation

Button

Alanine Transaminase

http://download.lww.com/wolterskluwer_vitalstream_com/animation_library/HP-09-alanine_glucose/alanineglucose.html

7. The Metabolic Mill

§  The citric acid cycle is a vital link between food energy and the chemical energy of ATP.

§  The citric acid cycle also provides intermediates that cross the mitochondrial membrane into the cytosol to synthesize bio-nutrients.

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BPK 312 Nutrition for Fitness & Sport

Lecture 3 Summary Slide

Nutrient Roles in Bioenergetics

1.  Learning Objectives for Lecture 3

2.  Bioenergetics/Conservation of Energy

3.  Redox Reactions

4.  ATP/Phosphocreatine

5.  Cellular Oxidation/Electron Transport/Oxidative Phosphorylation

6.  Energy Release from Macronutrients

7.  Metabolic Mill 36

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