rate-limiting enzyme

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1. What do you think the
word bioenergetics
means? Why?
2. Infer how bioenergetics
relates to muscles.
Fuel for Exercise:
Bioenergetics and Muscle
Metabolism
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): carbohydrate, fat
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 but slow ATP production
– Must be broken down into free fatty acids (FFAs)
and glycerol
– Only FFAs are used to make ATP
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
1. What is going to give off
more energy? Fats or
carbohydrates? Why?
2. What is harder to break
down proteins or fat?
Figure 2.1
Controlling 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 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
Figure 2.2
Controlling 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
Figure 2.3
Stored 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)
1. What two substrates give
off the same amount of
energy? How much is it?
2. What does an enzyme do
for us?
1. What is ATP made of?
2. Draw the structure.`
1. What are the three
pathways we use to
synthesize ATP?
2. Which are anaerobic and
which are aerobic?
1. Write the equation for the
breakdown of ATP.
2. What is ATPase? Using
your answer explain what
it does in a chemical
reaction.
1. Write down one similarity
and one difference we
found on Friday.
2. When do you think these
different energy sources
are used?
Three ways to create ATP
• ATP-PC (high power, short duration)
• Glycolytic (moderate power/short
duration)
• Oxidative (low power/long duration).
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 can be used to reassemble ATP
• Replenishes ATP stores during rest
• Recycles ATP during exercise until used
up (~3-15 s maximal exercise)
• Examples: a short sprint, a punch or kick, or
pitching a baseball.
Figure 2.5
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
• ATP yield: 2 to 3 mol ATP/1 mol substrate
• Duration: 15 s to 2 min
• Breakdown of glucose via glycolysis
• Examples: any moderately-long runs such as
200-400 yards, a 1:30 effort of all-out MMA
maneuvers, or a one-minute full-court press offense display - and another full-court press
effort in basketball.
Glycolytic System
• Uses glucose or glycogen as its
substrate
– Costs 1 ATP for glucose, 0 ATP for glycogen
• Pathway starts with glucose, ends with
pyruvic acid
– 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
• Pros
– Allows muscles to contract when O2 is 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
• Aerobic
Oxidative System
• 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
Oxidation of Carbohydrate
• Stage 1: Glycolysis
• Stage 2: Krebs cycle
• Stage 3: Electron transport
chain
Oxidation of Carbohydrate:
• 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:
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
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
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
– Generally minimal
Control of Oxidative Phosphorylation:
Negative Feedback
• Negative feedback regulates Krebs
cycle
• Isocitrate dehydrogenase: ratelimiting enzyme
– Similar to PFK for glycolysis
– Inhibited by ATP, activated by ADP
Figure 2.11
Figure 2.9
Figure 2.10
Figure 2.12
Interaction Among 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
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, the more of this the more
endurance. 2-4 times more in endurance runners.
• Endurance trained versus untrained
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
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
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