Fuel for Exercise:

Bioenergetics and Muscle

etabolism
 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
 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

 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)
 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): more fat, carbohydrate
 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
 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 (9.4 kcal/g) but slow ATP
production
– Must be broken down into free fatty acids (FFAs)
and glycerol
– Only FFAs are used to make ATP
 Body Stores of Carbohydrate

110g
451kcal

500g
2,050
kcal

15g
62kcal

Male, 65kg, 12% BF

 Body Stores of Fat

7800g 161g
73,320kcal 1,513kcal

Male, 65kg, 12% BF

 Protein

• Energy substrate during starvation

– 4.1 kcal/g
– Must be converted into glucose (gluconeogenesis)
to be used. But only use it during starvation by
breaking down muscle
– Protein  glucose = gluconeogenesis
– Protein  FFAs = lipegenesis

• Can also convert into FFAs (lipogenesis)

– For energy storage
– For cellular energy substrate
MIDTERM **Cellular Metabolism**

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
Enzyme Control

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
– Can create bottleneck at an early step
– Activity influenced by negative feedback
– Slows overall reaction, prevents runaway reaction
Metabolic Pathway Example

Figure 2.3
 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
– Can only use energy from ATP directly, so you cannot use fat carbs
protein as a direct fuel source
ATP

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

• 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
 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)
 **Phosphocreatine System**
for fast and short bursts, first system
used

Figure 2.5
ATP PCr During Exercise

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

• Anaerobic - no oxygen involved

• 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)   (increase) PFK activity
 ATP   (lower) PFK activity
– Also regulated by products of Krebs cycle

• Glycolysis = ~2 min maximal exercise

• Need another pathway for longer durations
Glycolytic System

Figure 2.7
 Oxidative System

• Aerobic – with oxygen

• ATP yield: depends on substrate
– 32 to 33 ATP/1 glucose (substrate) – fast process
– 100+ ATP/1 FFA (substrate) – slow process

• 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
Oxidation of Carbohydrate

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
 Oxidation of Carbohydrate:
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
Kreb’s Cycle

Figure 2.9
 Oxidation of Carbohydrate:
Electron 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****
Electron Transport Chain

Figure 2.10
 Oxidation of Carbohydrate:
Energy Yield

• 1 glucose = 32 ATP
• 1 glycogen = 33 ATP
• Breakdown of net totals***
– Glycolysis = +2 glucose [(or +3 (glycogen)] ATP
– GTP from Krebs cycle = +2 ATP
– 10 NADH = +25 ATP
– 2 FADH = +3 ATP
Oxidation of Glucose

Figure 2.11
 Oxidation of Fat

• Triglycerides: major fat energy source

(stores)
– 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
 b-Oxidation of Fat
• ^Beta oxidation^ = 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
ATP From One Molecule of Palmitic
Acid
Stage of Process Direct (substrate- Oxidative
level oxidation) Phosphorylation

Fatty acid activation 0 -2

Β-Oxidation 0 28
(occurs 7 times)

Krebs cycle 8 72
(occurs 8 times)

Subtotal 8 98
Total 106
 Oxidation of Protein

• Rarely used as a substrate

– Starvation
– Can be converted to glucose (gluconeogenesis)
– Can be converted to acetyl-CoA (krebs cycle)

• 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 (happens early – a few steps in)
– Similar to PFK for glycolysis
– Regulates electron transport chain
– Inhibited by ATP, activated by ADP
 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
– ATP-PCr – 2-15 seconds
– Glycolytic – 15s-2m
– Oxidative – 2+ min

• More cooperation during transition periods

Summary of Substrate Metabolism

Figure 2.12
Rate(speed) of ATP Production

100m 400m
5k marathon
Figure 2.13
Volume of ATP Production

Figure 2.13
Characteristics of the Energy Systems
Energy Oxygen? Chemical Relative ATP per Capacity
System Reaction rate of molecule
ATP/sec
ATP-PCr No PCr to Cr 10 1 <15 s
Sprint
Glycolysis No Glucose or 5 2-3 ~1 min
400 m glycogen to
lactate
Oxidative Yes Glucose or 2.5 (32-33) ~90 min
(CHO) glycogen to
5k run CO2 and
H2O
Oxidative Yes FFA or TG 1.5 >100 Days
(fat) to CO2 and Greater
marathon H2O than 100
 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 (SDH)
– Citrate synthase

• Endurance trained versus untrained

Enzyme Activity

Figure 2.14
 Fiber Type Composition
and Endurance Training

• Type I (marathon) fibers: greater oxidative

capacity
– More mitochondria
– High oxidative enzyme concentrations
– Type II (sprint) 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 limited—use it or lose it

• O2 levels entering and leaving the lungs
accurate estimate of O2 use in muscle
 Metabolic Flexibility

• The body’s ability to adapt the substrate

being used for fuel to changing fuel
availability and energy demands

• Metabolic inflexibility contributes to

metabolic diseases such as obesity, insulin
resistance, and type 2 diabetes