Fuel for Exercise:

Bioenergetics and Muscle

Metabolism

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

Measuring Energy Release

1 calorie (cal) is the amount of heat/energy
needed to raise 1g water by 1o C, from 14.5 to
15.5 0C.
Kilocalories (kcal): 1 kcal = 1,000 cal
Calorie (capital C) ~ kilocalorie
Eating/burning
1,000 cal = 1 kcal = 1 Calorie

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

Substrates: Fuel for Exercise

Carbohydrate, fat, protein
Carbon, hydrogen, oxygen, nitrogen

Energy from chemical bonds in food stored

in high-energy compound ATP
Cytosol
Mitochondria

Fuel usage dependent on the intensity and

duration of the activity (exercise)

Carbohydrate
All carbohydrate converted to glucose
4 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

Fat
Efficient substrate, efficient storage
9 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

Table 2.1

Protein
Energy substrate during starvation
4 kcal/g
Must be converted into glucose (gluconeogenesis)

Can also convert into FFAs (lipogenesis)

For energy storage
For cellular energy substrate
Provides 5 10% of energy needs

Figure 2.1

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

Controlling the Rate of Energy

Production by Enzyme Activity
Energy released at a controlled rate based
on enzyme activity in metabolic pathway
Enzymes

Proteins, highly specific

Do not start chemical reactions or set ATP yield
Do facilitate breakdown (catabolism) of substrates
Lower the activation energy for a chemical reaction
Enzyme names end with suffix -ase

ATP broken down by ATPase

Figure 2.2

Controlling the Rate of Energy

Production by Enzyme Activity
Each step in a biochemical pathway
requires specific enzyme(s)
More enzyme activity = more product
Rate-limiting enzyme
Activity influenced by negative feedback
Slows overall reaction, prevents runaway reaction

Figure 2.3

Animation 2.3

Video 2.1

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

Figure 2.4

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)

ATP-PCr System
Phosphagen Cycle / System
Anaerobic, substrate-level metabolism
Occurs in cytosol

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

ATP-PCr System
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)

Figure 2.5

Animation 2.5

Figure 2.6

Control of ATP-PCr System:

Creatine 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

Glycolytic System
Glycolysis
Anaerobic
Occurs in the cytosol

ATP yield: 2 to 3 mol ATP / 1 mol substrate

Duration: 15 s to 2 min
Breakdown of glucose via glycolysis

Glycolytic System
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

Glycolytic System
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

Glycolytic System
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

Oxidative System
Aerobic
ATP yield: depends on substrate
32 to 33 ATP/1 glucose
100+ ATP/1 FFA (depending on the FFA length)

Duration: steady supply for hours

Most complex of three bioenergetic systems
Occurs in the mitochondria, not cytoplasm

Oxidation of Carbohydrate
Stage 1: Glycolysis
Stage 2: Krebs cycle
Stage 3: Electron transport chain
Including oxidative phosphorylation

Figure 2.8

Oxidation of Carbohydrate:
Glycolysis 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

Krebs 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

Figure 2.9

Electron Transport Chain

H+, electrons carried to electron transport
chain via NADH, FADH molecules
Nicotinamide adenine dinucleotide
Flavin adenine dinucleotide

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

Oxidation of Carbohydrate:
Energy 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

Figure 2.10

Figure 2.11

Animation 2.11

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
Occurs in mitochondria only
Yields ~3 to 4 times more ATP than glucose
Slower than glucose oxidation

Fat: Triglycerides

-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

Oxidation of Fat:
Krebs 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

Table 2.2

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

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.

Control of Oxidative Phosphorylation:

Negative 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

Figure 2.12

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

Figure 2.13

Table 2.3

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

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

Type I fibers vs. type IIx fibers

Figure 2.14

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

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