Fuel for Exercise: Bioenergetics and Muscle Metabolism

1
Chapter 2

• Fuel for ExerciseBioenergetics and Muscle
  Metabolism

2
CHAPTER 2 Overview

• Substrates fuel for exercise
• Controlling the rate of energy production
• Storing energy high-energy phosphates
• Bioenergetics basic energy systems
• Interaction of the energy systems

3
Terminology

• Substrates
• Fuel sources from which we make energy (adenosine
  triphosphate ATP)
• Carbohydrate, fat, protein
• Bioenergetics
• Process of converting substrates into energy
• Performed at cellular level
• Metabolism chemical reactions in the body

4
Measuring Energy Release

• Can be calculated from heat produced
• 1 calorie (cal) heat energy required to raise 1
  g of water from 14.5 C to 15.5 C
• 1,000 cal 1 kcal 1 Calorie (dietary)

5
Substrates Fuel for Exercise

• Carbohydrate, fat, protein
• Carbon, hydrogen, oxygen, nitrogen
• Energy from chemical bonds in food stored in
  high-energy compound ATP
• Resting 50 carbohydrate, 50 fat
• Exercise (short) more carbohydrate
• Exercise (long) carbohydrate, fat

6
Carbohydrate

• All carbohydrate converted to glucose
• 4.1 kcal/g 2,500 kcal stored in body
• Primary ATP substrate for muscles, brain
• Extra glucose stored as glycogen in liver,
  muscles
• Glycogen converted back to glucose when needed to
  make more ATP
• Glycogen stores limited (2,500 kcal), must rely
  on dietary carbohydrate to replenish

7
Fat

• Efficient substrate, efficient storage
• 9.4 kcal/g
• 70,000 kcal stored in body
• Energy substrate for prolonged, less intense
  exercise
• High net ATP yield but slow ATP production
• Must be broken down into free fatty acids (FFAs)
  and glycerol
• Only FFAs are used to make ATP

8
Table 2.1
9
Protein

• Energy substrate during starvation
• 4.1 kcal/g
• Must be converted into glucose (gluconeogenesis)
• Can also convert into FFAs (lipogenesis)
• For energy storage
• For cellular energy substrate

10
Figure 2.1
11
Controlling the Rate of Energy Production by
Substrate Availability

• Energy released at a controlled rate based on
  availability of primary substrate
• Mass action effect
• Substrate availability affects metabolic rate
• More available substrate higher pathway
  activity
• Excess of given substrate cells rely on that
  energy substrate more than others
• (continued)

12
Controlling the Rate of Energy Production by
Enzyme Activity

• Energy released at a controlled rate based on
  enzyme activity in metabolic pathway
• Enzymes
• Do not start chemical reactions or set ATP yield
• Do facilitate breakdown (catabolism) of
  substrates
• Lower the activation energy for a chemical
  reaction
• End with suffix -ase
• ATP broken down by ATPase
• (continued)

13
Figure 2.2
14
Controlling the Rate of Energy Production by
Enzyme Activity (continued)

• Each step in a biochemical pathway requires
  specific enzyme(s)
• More enzyme activity more product
• Rate-limiting enzyme
• Can create bottleneck at an early step
• Activity influenced by negative feedback
• Slows overall reaction, prevents runaway reaction

15
Figure 2.3
16
Animation 2.3
17
Video 2.1
18
Storing Energy High-Energy Phosphates

• ATP stored in small amounts until needed
• Breakdown of ATP to release energy
• ATP water ATPase ? ADP Pi energy
• ADP lower-energy compound, less useful
• Synthesis of ATP from by-products
• ADP Pi energy ? ATP (via phosphorylation)
• Can occur in absence or presence of O2

19
Figure 2.4
20
Bioenergetics Basic Energy Systems

• ATP storage limited
• Body must constantly synthesize new ATP
• Three ATP synthesis pathways
• ATP-PCr system (anaerobic metabolism)
• Glycolytic system (anaerobic metabolism)
• Oxidative system (aerobic metabolism)

21
ATP-PCr System

• Anaerobic, substrate-level metabolism
• ATP yield 1 mol ATP/1 mol PCr
• Duration 3 to 15 s
• Because ATP stores are very limited, this pathway
  is used to reassemble ATP
• (continued)

22
ATP-PCr System (continued)

• Phosphocreatine (PCr) ATP recycling
• PCr creatine kinase ? Cr Pi energy
• PCr energy cannot be used for cellular work
• PCr energy can be used to reassemble ATP
• Replenishes ATP stores during rest
• Recycles ATP during exercise until used up (3-15
  s maximal exercise)

23
Figure 2.5
24
Animation 2.5
25
Figure 2.6
26
Control of ATP-PCr SystemCreatine Kinase (CK)

• PCr breakdown catalyzed by CK
• CK controls rate of ATP production
• Negative feedback system
• When ATP levels ? (ADP ?), CK activity ?
• When ATP levels ?, CK activity ?

27
Glycolytic System

• Anaerobic
• ATP yield 2 to 3 mol ATP / 1 mol substrate
• Duration 15 s to 2 min
• Breakdown of glucose via glycolysis
• (continued)

28
Glycolytic System (continued)

• Uses glucose or glycogen as its substrate
• Must convert to glucose-6-phosphate
• Costs 1 ATP for glucose, 0 ATP for glycogen
• Pathway starts with glucose-6-phosphate, ends
  with pyruvic acid
• 10 to 12 enzymatic reactions total
• All steps occur in cytoplasm
• ATP yield 2 ATP for glucose, 3 ATP for glycogen
• (continued)

29
Glycolytic System (continued)

• Cons
• Low ATP yield, inefficient use of substrate
• Lack of O2 converts pyruvic acid to lactic acid
• Lactic acid impairs glycolysis, muscle
  contraction
• Pros
• Allows muscles to contract when O2 limited
• Permits shorter-term, higher-intensity exercise
  than oxidative metabolism can sustain
• (continued)

30
Glycolytic System (continued)

• Phosphofructokinase (PFK)
• Rate-limiting enzyme
• ? ATP (? ADP) ? ? PFK activity
• ? ATP ? ? PFK activity
• Also regulated by products of Krebs cycle
• Glycolysis 2 min maximal exercise
• Need another pathway for longer durations

31
Oxidative System

• Aerobic
• ATP yield depends on substrate
• 32 to 33 ATP/1 glucose
• 100 ATP/1 FFA
• Duration steady supply for hours
• Most complex of three bioenergetic systems
• Occurs in the mitochondria, not cytoplasm

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Oxidation of Carbohydrate

• Stage 1 Glycolysis
• Stage 2 Krebs cycle
• Stage 3 Electron transport chain

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Figure 2.8
34
Oxidation of CarbohydrateGlycolysis Revisited

• Glycolysis can occur with or without O2
• ATP yield same as anaerobic glycolysis
• Same general steps as anaerobic glycolysis but,
  in the presence of oxygen,
• Pyruvic acid ? acetyl-CoA, enters Krebs cycle

35
Oxidation of CarbohydrateKrebs Cycle

• 1 Molecule glucose ? 2 acetyl-CoA
• 1 molecule glucose ? 2 complete Krebs cycles
• 1 molecule glucose ? double ATP yield
• 2 Acetyl-CoA ? 2 GTP ? 2 ATP
• Also produces NADH, FADH, H
• Too many H in the cell too acidic
• H moved to electron transport chain

36
Figure 2.9
37
Oxidation of CarbohydrateElectron Transport
Chain

• H, electrons carried to electron transport chain
  via NADH, FADH molecules
• H, electrons travel down the chain
• H combines with O2 (neutralized, forms H2O)
• Electrons O2 help form ATP
• 2.5 ATP per NADH
• 1.5 ATP per FADH

38
Oxidation of CarbohydrateEnergy Yield

• 1 glucose 32 ATP
• 1 glycogen 33 ATP
• Breakdown of net totals
• Glycolysis 2 (or 3) ATP
• GTP from Krebs cycle 2 ATP
• 10 NADH 25 ATP
• 2 FADH 3 ATP

39
Figure 2.10
40
Figure 2.11
41
Animation 2.11
42
Oxidation of Fat

• Triglycerides major fat energy source
• Broken down to 1 glycerol 3 FFAs
• Lipolysis, carried out by lipases
• Rate of FFA entry into muscle depends on
  concentration gradient
• Yields 3 to 4 times more ATP than glucose
• Slower than glucose oxidation

43
b-Oxidation of Fat

• Process of converting FFAs to acetyl-CoA before
  entering Krebs cycle
• Requires up-front expenditure of 2 ATP
• Number of steps depends on number of carbons on
  FFA
• 16-carbon FFA yields 8 acetyl-CoA
• Compare 1 glucose yields 2 acetyl-CoA
• Fat oxidation requires more O2 now, yields far
  more ATP later

44
Oxidation of FatKrebs Cycle, Electron Transport
Chain

• Acetyl-CoA enters Krebs cycle
• From there, same path as glucose oxidation
• Different FFAs have different number of carbons
• Will yield different number of acetyl-CoA
  molecules
• ATP yield will be different for different FFAs
• Example for palmitic acid (16 C) 106 ATP net
  yield

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Table 2.2
46
Oxidation of Protein

• Rarely used as a substrate
• Starvation
• Can be converted to glucose (gluconeogenesis)
• Can be converted to acetyl-CoA
• Energy yield not easy to determine
• Nitrogen presence unique
• Nitrogen excretion requires ATP expenditure
• Generally minimal, estimates therefore ignore
  protein metabolism

47
Lactate Utilization

• Lactate is an important fuel during exercise.
• Muscles can utilize lactate in 3 ways
• Lactate produced in the cytoplasm can be taken up
  by the mitochondria of the same muscle fiber and
  oxidized.
• Lactate can be transported via MCP transporters
  to another cell and oxidized there (lactate
  shuttle).
• Lactate can recirculate back to the liver,
  reconverted to pyruvate and then to glucose
  through gluconeogenesis.

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Control of Oxidative PhosphorylationNegative
Feedback

• Negative feedback regulates Krebs cycle
• Isocitrate dehydrogenase rate-limiting enzyme
• Similar to PFK for glycolysis
• Regulates electron transport chain
• Inhibited by ATP, activated by ADP

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Figure 2.12
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Interaction of the Energy Systems

• All three systems interact for all activities
• No one system contributes 100, but
• One system often dominates for a given task
• More cooperation during transition periods

51
Figure 2.13
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Table 2.3
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The Oxidative Capacity of Muscle

• Not all muscles exhibit maximal oxidative
  capabilities
• Factors that determine oxidative capacity
• Enzyme activity
• Fiber type composition, endurance training
• O2 availability versus O2 need

54
Enzyme Activity

• Not all muscles exhibit optimal activity of
  oxidative enzymes
• Enzyme activity predicts oxidative potential
• Representative enzymes
• Succinate dehydrogenase
• Citrate synthase
• Endurance trained versus untrained

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Figure 2.14
56
Fiber Type Composition and Endurance Training

• Type I fibers greater oxidative capacity
• More mitochondria
• High oxidative enzyme concentrations
• Type II better for glycolytic energy production
• Endurance training
• Enhances oxidative capacity of type II fibers
• Develops more (and larger) mitochondria
• More oxidative enzymes per mitochondrion

57
Oxygen Needs of Muscle

• As intensity ?, so does ATP demand
• In response
• Rate of oxidative ATP production ?
• O2 intake at lungs ?
• O2 delivery by heart, vessels ?
• O2 storage limiteduse it or lose it
• O2 levels entering and leaving the lungs accurate
  estimate of O2 use in muscle