Download oxidation - mustafaaltinisik.org.uk

Document related concepts

Butyric acid wikipedia , lookup

Thylakoid wikipedia , lookup

NADH:ubiquinone oxidoreductase (H+-translocating) wikipedia , lookup

Fatty acid synthesis wikipedia , lookup

Mitochondrion wikipedia , lookup

Glucose wikipedia , lookup

Photosynthesis wikipedia , lookup

Photosynthetic reaction centre wikipedia , lookup

Metalloprotein wikipedia , lookup

Electron transport chain wikipedia , lookup

Fatty acid metabolism wikipedia , lookup

Myokine wikipedia , lookup

Light-dependent reactions wikipedia , lookup

Ketosis wikipedia , lookup

Microbial metabolism wikipedia , lookup

Adenosine triphosphate wikipedia , lookup

Basal metabolic rate wikipedia , lookup

Citric acid cycle wikipedia , lookup

Biochemistry wikipedia , lookup

Metabolism wikipedia , lookup

Evolution of metal ions in biological systems wikipedia , lookup

Oxidative phosphorylation wikipedia , lookup

Glycolysis wikipedia , lookup

Transcript
Review of Bioenergetics
SP5005 Physiology
Alex Nowicky
power point slides: Powers and
Howley- Exercise Physiology Ch 3
and 4
1
What is bioenergetics?






Study of energy in living systems
what it is?
Where does it come from?
How is it measured?
How is it produced and used by human
body at rest and during exercise?
Part of science of biochemistry -studies
conversion of matter into energy by
2
living systems
For your own study use any ex
physiology text and cover the
following:




Energy sources
recovery from exercise
measurement of energy, work and
power
This lecture is an overview of these!
3
Aim: review energy metabolism
Learning outcomes
 ATP is central to all energy transactions
 Oxidation (O2) (in mitochondria) central
 define aerobic and anaerobic pathways
- systems of enzymes and their
regulation
 fate of fuels - CHO, fats and proteinsrelative yields of useful energy (ATP)
4
Learning outcomes (con’t)




role of glycogenolysyis, -oxidation,
gluconeogenesis
indirect calorimetry for monitoring
energy expenditure- oxygen
consumption- (RER)
contribution of fuel supply during
exercise (short vs. long duration)
role aerobic and anaerobic systems
during exercise and recovery
5
Metabolism

Total of all chemical reactions that occur
in the body
– Anabolic reactions
• Synthesis of molecules
– Catabolic reactions
• Breakdown of molecules

Bioenergetics- oxidation (O2)
– Converting foodstuffs (fats, proteins,
carbohydrates) into energy
6
Cellular Chemical Reactions

Endergonic reactions
– Require energy to be added

Exergonic reactions
– Release energy

Coupled reactions
– Liberation of energy in an exergonic
reaction drives an endergonic reaction
7
The Breakdown of Glucose:
An Exergonic Reaction
8
Coupled Reactions
9
Enzymes

Catalysts that regulate the speed of
reactions
– Lower the energy of activation

Factors that regulate enzyme activity
– Temperature (what happens with changes
in T?)
– pH ( what happens with changes in pH?)

Interact with specific substrates
– Lock and key model
10
Fuels for Exercise

Carbohydrates
– Glucose
• Stored as glycogen in liver and muscle

Fats
– Primarily fatty acids
• Stored as triglycerides- adipose tissue and
muscles

Proteins
– Not a primary energy source during
exercise
11
High-Energy Phosphates

Adenosine triphosphate (ATP)
– Consists of adenine, ribose, and three
linked phosphates

Formation
ADP + Pi  ATP

Breakdown
ATP
ATPase
ADP + Pi + Energy
12
Model of ATP as the Universal
Energy Donor
13
Carbohydrate
w Readily available (if included in diet) and easily
metabolized by muscles
w Ingested, then taken up by muscles and liver and
converted to glycogen
w Glycogen stored in the liver is converted back to
glucose as needed and transported by the blood to
the muscles to form ATP
14
Fat (triglycerides)
w Provides substantial energy during prolonged, lowintensity activity- light weight (little water in storage)
w Body stores of fat are larger than carbohydrate reserves
w Less accessible for metabolism because it must be
reduced to glycerol and free fatty acids (FFA)
w Only FFAs are used to form ATP- triglycerides- must be
broken down by process of lipolysis
15
Protein - Body uses little protein during rest and exercise
(less than 5% to 10%).
w Can be used as energy source if converted to
glucose via glucogenesis (or gluconeogenesis)
w Can generate FFAs in times of starvation through
lipogenesis
w Only basic units of protein—amino acids—can be
used for energy- via transamination feed into Kreb’s cycle
• waste produce is ammonia - must be excreted (as urea)
16
Oxidation of Fat- FFA via - oxidation
w Lypolysis—breakdown of triglycerides into glycerol and
free fatty acids (FFAs).
w FFAs travel via blood to muscle fibers and are broken
down by enzymes in the mitochondria into acetyl CoA.
w Acetyl CoA enters the Krebs cycle and the electron
transport chain.
w Fat oxidation requires more oxygen and generates more
energy than carbohydrate oxidation.
17
What Determines Oxidative Capacity?
w Oxidative enzyme activity within the muscle
w Fiber-type composition and number of mitochondria
w Endurance training
w Oxygen availability and uptake in the lungs
18
Bioenergetics

Formation of ATP
– Phosphocreatine (PC) breakdown
– Degradation of glucose and glycogen (glycolysis)
– Oxidative formation of ATP

Anaerobic pathways
– Do not involve O2
– PC breakdown and glycolysis (lactate)

Aerobic pathways- only occur in mitochondria
– Electron transport system (ETS) -Requires O2
– Oxidative phosphorylation
19
Anaerobic ATP Production

ATP-PC system
– Immediate source of ATP
PC + ADP

Creatine kinase
ATP + C
Glycolysis
– Energy investment phase
• Requires 2 ATP
– Energy generation phase
• Produces ATP, NADH (carrier molecule), and
pyruvate or lactate
20
RECREATING ATP WITH PCr
21
ATP AND PCr DURING SPRINTING
What does
this show?
22
The Two Phases of Glycolysis
23
Glycolysis:
Energy Investment Phase
24
Glycolysis:
Energy Generation Phase
25
Oxidation-Reduction Reactions

Oxidation
– Molecule accepts electrons (along with H+)

Reduction
– Molecule donates electrons

Nicotinomide adenine dinucleotide (NAD)
NAD + 2H+  NADH + H+

Flavin adenine dinucleotide (FAD)
FAD + 2H+  FADH2
26
Production of Lactic Acid

Normally, O2 is available in the
mitochondria to accept H+ (and
electrons) from NADH produced in
glycolysis
– In anaerobic pathways, O2 is not available

H+ and electrons from NADH are
accepted by pyruvic acid to form lactic
acid
27
Conversion of Pyruvic Acid to
Lactic Acid
28
Aerobic ATP Production

Krebs cycle (citric acid cycle)
– Completes the oxidation of substrates and
produces NADH and FADH to enter the electron
transport chain

Electron transport chain
– Electrons removed from NADH and FADH are
passed along a series of carriers to produce ATP
– H+ from NADH and FADH are accepted by O2 to
form water
29
3 Stages of
Oxidative
Phosphorylation
30
The Krebs Cycle
31
Glycogen Breakdown and Synthesis
Glycolysis—Breakdown of glucose; may be anaerobic or
aerobic
Glycogenesis—Process by which glycogen is synthesized
from glucose to be stored in the liver
Glycogenolysis—Process by which glycogen is broken
into glucose-1-phosphate to be used by muscles
Gluco(neo)genesis- formation of glucose from lipids and
proteins via intermediates (lactate, pyruvate, amino acids)
32
Relationship Between the Metabolism of
Proteins, Fats, and Carbohydrates
33
The Chemiosmotic Hypothesis of
ATP Formation
34
Aerobic ATP yield from glucose
Metabolic Process
High-Energy
Products
ATP from Oxidative ATP Subtotal
Phosphorylation
Glycolysis
2 ATP
2 NADH
—
6
2 (if anaerobic)
8 (if aerobic)
6
14
—
18
4
16
34
38
Pyruvic acid to acetyl-CoA 2 NADH
Krebs cycle
Grand Total
2 GTP
6 NADH
2 FADH
38
35
Summary- Oxidation of Carbohydrate
1. Pyruvic acid from glycolysis is converted to acetyl
coenzyme A (acetyl CoA).
2. Acetyl CoA enters the Krebs cycle and forms 2 ATP,
carbon dioxide, and hydrogen.
3. Hydrogen in the cell combines with two coenzymes that
carry it to the electron transport chain.
4. Electron transport chain recombines hydrogen atoms to
produce ATP and water.
5. One molecule of glycogen can generate up to 39
molecules of ATP.
36
Summary (con’t) - Oxidation of Fat
w Lypolysis—breakdown of triglycerides into glycerol and
free fatty acids (FFAs).
w FFAs travel via blood to muscle fibers and are broken
down by enzymes in the mitochondria into acetic acid
which is converted to acetyl CoA.
w Acetyl CoA enters the Krebs cycle and the electron
transport chain.
w Fat oxidation requires more oxygen and generates more
energy than carbohydrate oxidation.
37
Stop for 10 min break
Any questions?
38
Kilocalorie and other units (SI)
w Energy in biological systems is measured in kilocalories.
w 1 kilocalorie is the amount of heat energy needed to raise
1 kg of water 1°C at 15 °C. 1kcal= 1000cal
Work - energy - application of force through a distance
Should be using SI units
1 Joule (J) = 1 N-m/s2
1 kg-m = 1kg moved through 1 metre
1kcal = 426 kg-m = 4.186kiloJoules (kJ)
1 kJ = 0.2389 kcal ( 1kcal = 4.186kJ)
1 litre of O2 consumed = 5.05kcal= 21.14 kJ
(1ml of oxygen = .005kcal) - useful conversion factor
39
Power to perform uses up energy- how
much oxygen consumption to supply
energy?
Power - work/time (Watts or hp)
1hp = 745 watts= 10.7kcal/min
1L of oxygen/min consumption= 5.05kcal/min= 21 kJ/min
1MET = 3.5ml oxygen/kg/min= 0.0177kcal/kg/min
15 kcal/min= ? Oxygen/min (can you do this?)
40
CARBOHYDRATE vs FAT
1 gram of CHO--> 4 kcal
1 gram of FFA (palmitic acid)--> 9 kcal
41
Body Stores of Fuels and Energy
g
Carbohydrates
Liver glycogen
Muscle glycogen
Glucose in body fluids
Fat
Subcutaneous
Total
Intramuscular
Total
kcal
grams
kcal
110
250
451
1,025
15
62
375
1,538
7,800
161
70,980
1,465
7,961
72,445
Note. These estimates are based on an average body weight of 65 kg
(143 lb) with 12% body fat.
42
Oxygen consumption for Carbohydrate
(glucose from glycogen)
(C6H1206)n + 6 O2 --> 6 CO2 +6 H20 + 39 ATP
6 moles of O2 needed to break down 1 mole of glycogen
6 moles x 22.4 l/mole oxygen = 134.4 l
134.4l/39 moles of ATP = 3.45 l/mole ATP
at rest takes about 10-15 min,
during max exercise takes about 1 min
ratio (RQ) carbon dioxide/oxygen = 6/6 = 1
43
Aerobic ATP yield from FFA (free
fatty acid - palmitic acid (16C)
16C  7 Acyl coA  7 acetyl coA
(C16H3202) + 23 O2 --> 16 CO2 +16 H20 + 130 ATP
23 moles of O2 needed to break down 1 of palmitic acid
23 moles x 22.4 l/mole oxygen = 512.2 l
512l/130 moles of ATP = 3.96 l O2/mole ATP
ratio of carbon dioxide/oxygen = 16/23 = 0.7
15% more oxygen than metabolising glycogen, but
advantage is light weight (little water) storage
44
How do we determine efficiency of ox
phos- respiration (metabolism of
glucose)?
Efficiency =
38moles ATP x 7.3kcal/mole ATP
686 kcal/mole glucose

= 0.4 x100% = 40% (60% lost heat)
how does this compare to mechanical
engine?
45
Control of Bioenergetics

Rate-limiting enzymes
– An enzyme that regulates the rate of a
metabolic pathway

Levels of ATP and ADP+Pi
– High levels of ATP inhibit ATP production
– Low levels of ATP and high levels of
ADP+Pi stimulate ATP production

Calcium may stimulate aerobic ATP
production
46
Action of Rate-Limiting Enzymes
47
Control of Metabolic Pathways
Pathway
Rate-Limiting
Enzyme
Stimulators
Inhibitors
ATP-PC system
Creatine kinase
ADP
ATP
Glycolysis
Phosphofructokinase AMP, ADP, Pi, pH ATP, CP, citrate, pH
Krebs cycle
Isocitrate
dehydrogenase
++
ADP, Ca , NAD
Electron transport Cytochrome Oxidase ADP, Pi
chain
ATP, NADH
ATP
48
Interaction Between Aerobic and
Anaerobic ATP Production


Energy to perform exercise comes from an
interaction between aerobic and anaerobic
pathways
Effect of duration and intensity
– Short-term, high-intensity activities
• Greater contribution of anaerobic energy systems
– Long-term, low to moderate-intensity exercise
• Majority of ATP produced from aerobic sources
49
Maximal capacity and power of
three energy systems
System
phosphagen
anaerobic glycolysis
aerobic (from glycogen)
moles ATP/min
power capacity
3.6
1.6
1.0
0.7
1.2
90.0
at rest - aerobic system supplies ATP with
oxygen consumption about 0.3L/min, blood
lactate remains constant
50
Contribution
of energy
systems
51
Rest-to-Exercise Transitions

Oxygen uptake increases rapidly
– Reaches steady state within 1-4 minutes

Oxygen deficit
– Lag in oxygen uptake at the beginning of
exercise
– Suggests anaerobic pathways contribute to
total ATP production

After steady state is reached, ATP
requirement is met through aerobic ATP
production
52
The Oxygen Deficit
53
Differences in VO2 Between Trained
and Untrained Subjects- Why?
54
Recovery From Exercise:
Metabolic Responses

Oxygen debt
– Elevated VO2 for several minutes immediately following
exercise
– Excess post-exercise oxygen consumption (EPOC)

“Fast” portion of O2 debt
– Resynthesis of stored PC
– Replacing muscle and blood O2 stores

“Slow” portion of O2 debt
– Elevated body temperature and catecholamines
– Conversion of lactic acid to glucose (gluconeogenesis)
55
Oxygen Deficit and Debt During
Light-Moderate and Heavy Exercise
56
Factors Contributing to EPOC
57
Metabolic Response to Exercise:
Short-Term Intense Exercise

High-intensity, short-term exercise
(2-20 seconds)
– ATP production through ATP-PC system

Intense exercise longer than 20 seconds
– ATP production via anaerobic glycolysis

High-intensity exercise longer than 45
seconds
– ATP production through ATP-PC, glycolysis,
and aerobic systems
58
Metabolic Response to Exercise:
Prolonged Exercise

Exercise longer than 10 minutes
– ATP production primarily from aerobic
metabolism
– Steady state oxygen uptake can generally
be maintained

Prolonged exercise in a hot/humid
environment or at high intensity
– Steady state not achieved
– Upward drift in oxygen uptake over time
59
Metabolic Response to Exercise:
Incremental Exercise

Oxygen uptake increases linearly until
VO2max is reached
– No further increase in VO2 with increasing
work rate

Physiological factors influencing VO2max
– Ability of cardiorespiratory system to
deliver oxygen to muscles
– Ability of muscles to take up the oxygen
and produce ATP aerobically
60
Changes in Oxygen Uptake With
Incremental Exercise- explain?
61
Estimation of Fuel Utilization During
Exercise- from overall equations

Respiratory exchange ratio (RER or R)
– VCO2 / VO2
– Indicates fuel utilization
• 0.70 = 100% fat
• 0.85 = 50% fat, 50% CHO
• 1.00 = 100% CHO

During steady state exercise
– VCO2 and VO2 reflective of O2
consumption and CO2 production at the
cellular level
62
Exercise Intensity and Fuel
Selection

Low-intensity exercise (<30% VO2max)
– Fats are primary fuel

High-intensity exercise (>70% VO2max)
– CHO are primary fuel

“Crossover” concept
– Describes the shift from fat to CHO
metabolism as exercise intensity increases
– Due to:
• Recruitment of fast muscle fibers
• Increasing blood levels of epinephrine
63
Illustration of the “Crossover”
Concept
64
Exercise Duration and Fuel
Selection


During prolonged exercise there is a
shift from CHO metabolism toward fat
metabolism
Increased rate of lipolysis
– Breakdown of triglycerides into glycerol
and free fatty acids (FFA)
– Stimulated by rising blood levels of
epinephrine
65
Shift From CHO to Fat Metabolism
During Prolonged Exercise
66
Interaction of Fat and CHO
Metabolism During Exercise


“Fats burn in the flame of carbohydrates”
Glycogen is depleted during prolonged
high-intensity exercise
– Reduced rate of glycolysis and production of
pyruvate
– Reduced Krebs cycle intermediates
– Reduced fat oxidation
• Fats are metabolized by Krebs cycle
67
Sources of Fuel During Exercise

Carbohydrate
– Blood glucose
– Muscle glycogen

Fat
– Plasma FFA (from adipose tissue lipolysis)
– Intramuscular triglycerides

Protein
– Only a small contribution to total energy production
(only ~2%)
• May increase to 5-15% late in prolonged exercise

Blood lactate
– Gluconeogenesis in liver
68
Effect of Exercise Intensity on
Muscle Fuel Source
What does this
graph show?
69
Effect of Exercise Duration on
Muscle Fuel Source- summarise
70
Summary






Aerobic and anaerobic systems
What regulates metabolic pathways?
What is the RER?
Describe how fuel utilisation is affected
by intensity and duration of exercise
What happens during recovery from
exercise?
A note about ATP yield- some sources
say 38 some say 36 with aerobic resp 71