Lecture 9 – Cellular Respiration
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First…watch this video. Seriously.
http://www.khanacademy.org/video/introductionto-cellular-respiration?playlist=Biology
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In this lecture
• Cellular respiration
• Redox reactions
• Glycolysis
– Pyruvate oxidation
• Krebs Cycle
• Electron Transport Chain
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Why do we do respiration?
• Cellular respiration provides most of our ATP
• The components of our diet provides the
reactants for cellular respiration
– Glucose is what we’ll study today
– Lipids and protein breakdown will be briefly
covered, and studied more in depth in another
course
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Biochemical pathways are:
Exergonic and endergonic reactions
Oxidation and reduction reactions
Enzymatic reactions
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The Big Picture
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From food to ATP
• Amylase in saliva starts to break down starches
to disaccharides
• Stomach acid breaks apart large structures such
as cells and intercellular structures
• Amylase in the small intestine completes the
breakdown of all carbohydrates to disaccharides
• Maltases, lactases, and sucrases break down
disaccharides into monosaccharides
• Glucose is brought to all the cells in the body
through the circulatory system
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Energy production sites in the cell
• Glucose is brought inside the cell by
cotransport with sodium
• The mitochondria are where ATP is produced
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Electron energy levels
• An electron loses potential energy when it
shifts to a more electronegative atom
C6H12O6 + 6O2
6CO2 + 6H2O + energy
Here, electrons are transferred from carbon and hydrogen to
oxygen
The electrons in this reaction lose a LOT of potential energy
Carbohydrates and fats are high-energy foods because they
have a lot of electrons associated with hydrogen
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Figure 9.5
H2  1/2 O2

2H
Explosive
release of
heat and light
energy
Free energy, G
Free energy, G
(from food via NADH)
Controlled
release of
+

2H  2e
energy for
synthesis of
ATP
O2
1/
2
O2
ATP
ATP
ATP
2 e
2
H+
H2O
(a) Uncontrolled reaction
1/
2
H2O
(b) Cellular respiration
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The chemical reactions in respiration
The chemistry definition:
Oxidation and reduction
OIL
RIG
Oxidation is “losing”
Oxygen is
highly
electronegative
Reduction is “gaining”
What is being lost and gained? Electrons!
Electrons are usually lost to oxygen
Oxidation and reduction reactions often occur in a pair,
and together are called redox reactions
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The chemical reactions in respiration
The biology definition:
Oxidation and reduction
Losing a hydrogen atom
Gaining a hydrogen atom
In biochemical reactions, hydrogen is what usually gets
swapped around
Hydrogen almost always bonds to an atom that is more
electronegative (C, O, N, P), and so loses its electron
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Redox Reactions
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The chemical reactions in respiration
• Redox reactions
• Phosphorylation/dephosphorylation
– Carried out by kinases and phosphatases
– Phosphorylation increases chemical potential
energy and “primes” the molecule for work
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New players in the enzyme game
• NAD+ and NADH
• FAD and FADH2
NAD+ is derived
from niacin
NAD+ is a coenzyme
FAD is derived from riboflavin
NAD+ shuttles electrons through
the various stages of cellular
respiration
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NAD+ and FAD
reduction
NADH
NAD+
Oxidized
form
Reduced
form
oxidation
• NAD+ accepts electrons and becomes NADH
• NAD+ is reduced into NADH
• NADH is a reducing agent, and is recycled back to
NAD+ through oxidation
Each NADH (the reduced form of NAD+) represents
stored energy that is tapped to synthesize ATP.
Each NADH produces 3 ATPs in the e- transport chain
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What is cellular respiration?
Glucose
C6H12O6 + 6O2
Energy
- 686kcal/mol
6CO2 + 6H2O + energy
Cellular respiration
38 ATP
Heat
1 molecule of glucose produces 28 ATPs
Cellular respiration is the step-by-step
release and harness of the chemical
potential energy in glucose
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Redox Reactions in Cellular Respiration
During cellular respiration, the fuel (such as glucose) is
oxidized, and O2 is reduced
becomes oxidized
becomes reduced
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Two types of cellular respiration:
The breakdown of organic
molecules is always exergonic
• Aerobic respiration – takes place in the
presence of oxygen
• Anaerobic respiration – takes place in the
absence of oxygen
– Fermentation is a type of anaerobic respiration
where sugars are partially degraded
– Consumes compounds other than oxygen
Cellular respiration includes both aerobic and anaerobic respiration but is
often used to refer to aerobic respiration
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The stages of aerobic respiration
Consumes two ATP
Breaks glucose in
half
Rearranges the halfglucose molecule
Electrons from
glucose are passed
around
Glycolysis
Citric Acid Cycle*
Electron Transport
Chain
Net 2 ATP
Generates 4 ATP
Generates 2 ATP
Generates 34 ATP
*AKA the Krebs cycle and the TCA cycle
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The Big Picture
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Figure 9.6-1
Glycolysis
Electrons
carried
via NADH
Glycolysis
Glucose
Pyruvate
CYTOSOL
MITOCHONDRION
ATP
Substrate-level
phosphorylation
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Glycolysis
• The players:
The production of
ATP from ADP by
direct transfer of a
phosphate group
from a
phosphorylated
protein
– Glucose
– Pyruvate
– ADP/ATP
– Enzymes
• The processes:
– Substrate-level phosphorylation
• The locations
– Cytoplasm
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Glycolysis
Beginning structure:
- Breaking down of glucose
- Can be done with or without oxygen
End structures:
“glyco” = glucose
“lysis” = breaking
apart
Broken down into two stages:
• The “investment” phase (uses 2 ATP)
• The “payoff” phase (produces 2 ATP)
“You have toNSCC
spend
money to make money”
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
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Glycolysis
• Begin:
– Glucose
– NAD+
– ADP
• End:
– 2 pyruvate
– 2 NADH
– 2 ATP
Most of glycose’s original energy
is still present in pyruvate!
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Glycolysis
• In the presence of O2, pyruvate enters the
mitochondrion where the oxidation of glucose
is completed during TCA cycle
• Without O2, pyruvate undergoes fermentation
into either ethanol or lactic acid
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Glycolysis
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Pyruvate Oxidation
Glycolysis feeds into TCA cycle ONLY when oxygen is present!!
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Pyruvate Oxidation
• Before pyruvate can be fed into TCA cycle, it
must become acetyl-CoA (acetyl-coenzyme A)
• It does this through pyruvate oxidation
– Produces one NADH from NAD+
– Three-carbon pyruvate is converted into twocarbons + acetyl-CoA
Think of acetylCoA as a
transporter for
the carbon
atoms from
pyruvate
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Pyruvate Oxidation
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Pyruvate Oxidation
• Acetyl-CoA couples with oxaloacetate, the
first molecule in TCA cycle
• Acetyl-CoA + oxaloacetate = citrate
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The Citric Acid Cycle
• The players:
–
–
–
–
Acetyl-CoA
Oxaloacetate
Plus many more carbon skeleton intermediates
Enzymes
• The processes:
– Hydrolysis
– Redox reactions
• The locations:
– Mitochondrial matrix
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The Citric Acid Cycle
Begin:
End:
Oxaloacetate
Oxaloacetate
1 ADP
3 NAD+
1 FAD
1 ATP
3 NADH
1 FADH2
The citric acid cycle, also called the Krebs cycle,
completes the break down of pyruvate to CO2
The citric acid cycle has eight steps, each catalyzed by a specific enzyme
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The Citric Acid Cycle
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The Citric Acid Cycle
Step 1 and 2: Overview
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The Citric Acid Cycle
Step 1 and 2: In detail
CoA is recycled
here to go back
to pyruvate
oxidation
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The Citric Acid Cycle
Step 3 and 4: In detail and overview
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The Citric Acid Cycle
Step 5 and 6: Overview
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The Citric Acid Cycle
Step 5 and 6: In detail
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The Citric Acid Cycle
Step 7 and 8: Overview
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The Citric Acid Cycle
Step 7 and 8:
In detail
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The Citric Acid Cycle
• The citric acid cycle is the entry point for other
catabolic pathways
• Acetyl-CoA can be derived from carbohydrates,
proteins, and fats
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The Citric Acid Cycle
This is for one pyruvate. Remember, one glucose molecule produces two pyruvates!
• Begin:
• End:
– Acetyl-CoA
– Oxaloacetate
– 3NAD+
– 2 FAD
– 1ADP
The whole point of
TCA cycle is to
produce NADH
and FADH2
– 3 CO2s
– Oxaloacetate
– 3 NADH
– 2 FADH2
– 1 ATP
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The Citric Acid Cycle
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The electron transport chain
• The whole cellular process is about producing
ATP. Why do we care about NADH and
FADH2?
– These molecules then get oxidized in the electron
transport chain
– Every NADH will produce 3 ATP
– Every FADH2 will produce 2 ATP
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The electron transport chain
Begin:
End:
ADP
10 NADH
2 FADH2
ATP
10 NAD+
2 FAD
Electrons are passed along at lower and lower energy levels to release their energy
The electron transport chain breaks the large free-energy drop from food to O2
into smaller steps that release energy in manageable amounts
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The electron transport chain
• The players:
– FADH2, NADH, ADP
– ATP Synthase
– Cytochromes and membrane proteins
• The processes:
– Chemiosmosis
• The location:
– Intermembrane space of the mitochondria
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The electron transport chain
• The electron transport chain is a series of
proteins that pass along electrons
– Electrons come from NADH and FADH2
– Proteins are embedded in the matrix membrane
– Each time an electron is passed, it releases energy
– That energy is used to drive protons across the
membrane into the intermembrane space
– This creates an electrochemical gradient
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The electron transport chain
Energy increases
NADH  NAD+ + H+ + 2eCoQ, CytC, and
CytB are all
membrane proteins
on the inner matrix
membrane
CoQ
Release of energy
CytC
Release of energy
CytB
Release of energy
O2
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The electron transport chain
FADH2’s electrons are
lower energy than
NADH, and so enter
the electron transport
chain at a protein
further along in the
chain
The transport proteins alternate
reduced and oxidized states as they
accept and donate electrons
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Oxygen accepts those now
very-low energy electrons.
Oxygen is the terminal
electron acceptor
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The electron transport chain
• The release of energy is used to pump H+
across the matrix membrane into the
intermembrane space
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The electron transport chain
• H+ are pumped against their gradient using the
energy released from passing electrons to lower and
lower energy states
• This creates an electrochemical gradient
We can then
couple the
potential energy
in the
electrochemical
gradient to
another
biochemical
reaction
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The electron transport chain
• A bigger picture:
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The electron transport chain
What is that electrochemical gradient used for?
To create ATP!
How is that done?
Through a protein called ATP synthase
ATP synthase translates the potential energy in the electrochemical
gradient into the potential energy in the phosphate bonds of ATP
The flow of H+ with its electrochemical gradient is an exergonic reaction
ATP synthase couples an exergonic reaction with an endergonic reaction
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The electron transport chain
• ATP synthase is a turbine that
connects the flow of protons
to ADP  ATP
phosphorylation
• This is called chemiosmosis
Electrochemical energy  Kinetic energy  Chemical energy
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The electron transport chain
As the turbine turns with
the “current” of protons
flowing past, it
phosphorylates ADP into
ATP
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The electron transport chain
ATP Synthase: another view
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The electron transport chain
All together:
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The electron transport chain
• The energy stored in a H+ gradient across a
membrane couples the redox reactions of the
electron transport chain to ATP synthesis
• The H+ gradient is referred to as a proton-motive
force, emphasizing its capacity to do work
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Energy flows in this direction:
glucose  NADH  electron transport chain  proton-motive force  ATP
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What happens without oxygen?
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Fermentation
• Anaerobic respiration uses an electron
transport chain with a final electron acceptor
other than O2, for example sulfate
• Produces much less energy than aerobic
respiration
– Only source of ATP is substrate-level
phosphorylation
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Fermentation
• Two common types of fermentation:
– Lactic acid fermentation
• Lactic acid fermentation by some fungi and bacteria is used to
make cheese and yogurt
• Human muscle cells use lactic acid fermentation to generate ATP
when O2 is scarce
– Alcohol fermentation
• Alcohol fermentation by yeast is used in brewing,
winemaking, and baking
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Alcohol Fermentation
• Pyruvate is converted
to ethanol in two steps
– NADH produced in
glycolysis is oxidized
to NAD+
– Glucose is not
conpletely digested
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Lactic Acid Fermentation
• Pyruvate is
converted to
lactate in one
step
– NADH produced
during glycolysis
is oxidized to
NAD+
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Comparing Aerobic and Anaerobic
Respiration
Aerobic Respiration
Anaerobic Respiration
Glycolysis
Yes
Yes
Krebs Cycle
Yes
No
Electron Transport
Chain
Yes
No
ATP Production
32 per glucose
2 per glucose
NADH production
Yes
Yes
FADH2 production
Yes
No
Terminal electron
acceptor
O2
Pyruvate or acetaldehyde
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Who uses what pathway?
• Obligate anaerobes carry out fermentation or
anaerobic respiration and cannot survive in the
presence of O2
• Yeast and many bacteria are facultative anaerobes,
meaning that they can survive using either
fermentation or cellular respiration
• We require oxygen to live, and are obligate aerobes
• In a facultative anaerobe, pyruvate is a fork in the
metabolic road that leads to two alternative catabolic
routes
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Figure 9.18
Glucose
CYTOSOL
Glycolysis
Pyruvate
No O2 present:
Fermentation
O2 present:
Aerobic cellular
respiration
MITOCHONDRION
Ethanol,
lactate, or
other products
Acetyl CoA
Citric
acid
cycle
Catabolism of other biomolecules
• Proteins must be digested to
amino acids; amino groups
can feed glycolysis or the
citric acid cycle
• Fats are digested to glycerol
(used in glycolysis) and fatty
acids (used in generating
acetyl CoA)
• Fatty acids are broken down
by beta oxidation and yield
acetyl CoA
• An oxidized gram of fat
produces more than twice as
much ATP as an oxidized
gram of carbohydrate
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Controlling Respiration
ATP and citrate inhibit
phosphofructokinase
AMP is a positive allosteric
regulator of phosphofructokinase
If you have a lot of ATP or citrate (that
means a lot of energy) glycolysis is shut
down
If you have a lot of AMP (very little
energy is present) glycolysis is
stimulated
If ATP concentration begins to drop,
respiration speeds up; when there is
plenty of ATP, respiration slows down
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The Evolutionary Significance of
Glycolysis
• Ancient prokaryotes are thought to have used
glycolysis long before there was oxygen in the
atmosphere
• Very little O2 was available in the atmosphere until
about 2.7 billion years ago, so early prokaryotes likely
used only glycolysis to generate ATP
• Glycolysis is a very ancient process
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Vocabulary
•
•
•
•
•
•
•
•
Glycolysis
Krebs/TCA cycle
Redox reactions
Terminal electron acceptor
Chemiosmosis
Oxidative phosphorylation
Proton-motive force
Fermentation
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