Chapter 9
Cellular Respiration and
Fermentation
BIOL 1306
Chapter Outline
• 9.1 An Overview of Cellular Respiration
• Describe the four interconnected processes in cellular respiration and explain their central
role in catabolism and anabolism
• 9.2 Glycolysis: Oxidizing Glucose to Pyruvate
• Describe the process cells use to turn glucose into pyruvate
• 9.3 Processing Pyruvate to Acetyl CoA
• Describe the process cells use to turn pyruvate into acetyl CoA
• 9.4 The Citric Acid Cycle: Oxidizing Acetyl CoA to CO2
• Describe the pathway used by cells to fully oxidize the remaining two carbons from glucose
that are present in acetyl CoA
• 9.5 Electron Transport and Chemiosmosis: Building a Proton Gradient to Produce
ATP
• Analyze the relationship between the electron transport chain and oxidative phosphorylation
• 9.6 Fermentation
• Differentiate cellular respiration and fermentation in terms of inputs, outputs, and ATP
production
Introduction to Cellular Energy Production
• Life requires energy
• Life is fueled by adenosine
triphosphate (ATP)
• Has high potential energy
• Metabolic pathways harvest energy
from high-energy molecules, such as
glucose
• The energy released is used to add a
phosphate group to ADP to make ATP
9.1 An Overview of Cellular
Respiration
• Cells generally contain enough ATP
to sustain from 30 seconds to a few
minutes of activity
• ATP is unstable
• Most cells are making it all the time
• Cells obtain glucose to make ATP
• Plants produce glucose during
photosynthesis
• Other organisms obtain glucose
from food
• Organisms store glucose as glycogen
or starch
What Happens When Glucose Is Oxidized?
• Oxidized – loss of electrons
• When glucose is oxidized to carbon dioxide by burning, some energy is released
as heat and light:
C6H12O6 + 6 O2 → 6 CO2 + 6H2O + Heat and light
glucose oxygen carbon water
dioxide
• In cells, glucose is oxidized through a long series of carefully controlled redox
reactions:
• Much of the energy released is used to synthesize ATP
• These reactions comprise cellular respiration
• Cellular respiration is any set of reactions that uses electrons from high-energy
molecules to make ATP
• Two fundamental requirements of cells:
1. Energy source to generate ATP
2. A source of carbon to use as raw materials for synthesizing macromolecules
Cellular Respiration vs. Fermentation
• Fermentation utilizes a different metabolic pathway
• Fermentation also oxidizes glucose and produces ATP:
• Fermentation does not oxidize glucose fully
• Small, reduced organic molecules are produced as waste
• As a result, cellular respiration produces more energy than fermentation
does
The Four Processes of Cellular Respiration
Glycolysis—A six-carbon glucose is
broken down into two three-
carbon pyruvate molecules
Pyruvate processing—Each
pyruvate is oxidized to form acetyl
CoA
Citric acid cycle—Each acetyl CoA
is oxidized to CO2
Electron transport and oxidative
phosphorylation—Electrons move
through a transport chain and
their energy is used to set up a
proton gradient, which is used to
make ATP
Cellular Respiration Plays a Central Role in
Metabolism
• Catabolic pathways:
• Involve the breakdown of molecules
• Often harvest stored chemical energy to produce ATP
• Anabolic pathways:
• Result in the synthesis of larger molecules from smaller components
• Often use energy in the form of ATP
Catabolic Pathways Break Down a Variety of
Molecules
• Cellular respiration interacts
with other pathways
• For ATP production, cells:
• First use carbohydrates
• Then fats
• And finally proteins
• Proteins, carbohydrates, and
fats can all furnish substrates
for cellular respiration
Catabolic Pathways Break Down a Variety of
Molecules
• Fats are broken down into glycerol
and fatty acids:
• Glycerol can be processed and
enter glycolysis
• Fatty acids are converted to acetyl
CoA, which enters the citric acid
cycle
• Proteins are broken down into
amino acids:
• Amino groups are removed and
excreted as waste
• The remaining carbon compounds
are converted to pyruvate, acetyl,
or other intermediates
• Used in glycolysis and the citric
acid cycle
Cellular Respiration Interacts with Other
Catabolic and Anabolic Pathways
Catabolic Intermediates Are Used in Anabolic
Pathways
• Cellular respiration intermediates are used to synthesize
macromolecules:
• Glycolysis intermediates can be used to make nucleotides for DNA and RNA
synthesis
• Acetyl CoA may be used for synthesis of fatty acids to build phospholipids and
fats
• Many amino acids can be synthesized from citric acid cycle molecules
• Pyruvate can be used to make glucose for glycogen and starch production
• Metabolism comprises thousands of different chemical reactions
• Organizing them into pathways allows them to be regulated:
• Maintains a stable internal environment even under different environmental
conditions
• Referred to as homeostasis
9.2 Glycolysis: Oxidizing Glucose to Pyruvate
HISTORY ON GLYCOLYSIS
• Hans and Edward Buchner discovered glycolysis by accident in the
1890s
• Sucrose (table sugar) was added to preserve yeast extracts
• Unexpectedly, the sucrose was broken down and alcohol produced
• Further research showed phosphorylation was involved in the process
• Enzymes were also found to be key
• Observed in nearly every prokaryote and eukaryote
Glycolysis Is a Sequence of 10 Reactions
• Occur in the cytosol
• Three key points:
1. Glycolysis starts by using two ATP in the energy investment phase (reactions 1–5)
2. During the energy payoff phase (reactions 6–10), NADH is made and ATP is
produced by substrate-level phosphorylation
3. The net yield is two NADH, two ATP, and two pyruvate
Glycolysis Pathway
Table 9.1 The Reactions of Glycolysis
Step Enzyme Reaction
1 Hexokinase Uses ATP to phosphorylate glucose, increasing its potential energy.
2 Phosphoglucose Converts glucose-6-phosphate to fructose-6-phosphate; referred to as an isomer of glucose-6-phosphate.
isomerase
3 Phosphofructokinase Uses ATP to phosphorylate the opposite end of fructose-6-phosphate, increasing its potential energy.
4 Fructose-bis-phosphate Cleaves fructose-1,6-bisphosphate into two different 3-carbon sugars.
aldolase
5 Triose phosphate Converts dihydroxyacetone phosphate (DAP) to glyceraldehyde-3-phosphate (G3P). Although the reaction
isomerase is fully reversible, the DAP-to-G3P reaction is favored because G3P is immediately used as a substrate for
step 6.
6 Glyceraldehyde-3- In a two-step reaction, G3P is first oxidized using the NAD+ coenzyme to produce NADH. Energy from the
phosphate first reaction is used to attach a P i to the oxidized product to form 1,3-bisphosphoglycerate.
dehydrogenase
7 Phosphoglycerate kinase Transfers a phosphate from 1,3-bisphosphoglycerate to ADP to make 3-phosphoglycerate and ATP.
8 Phosphoglycerate Phosphoglycerate mutase Rearranges the phosphate in 3-phosphoglycerate to make 2-phosphoglycerate.
mutase
9 Enolase Removes a water molecule from 2-phosphoglycerate to form a c double bond t o c double bond and produce
phosphoenolpyruvate.
10 Pyruvate kinase Transfers a phosphate from phosphoenolpyruvate to ADP to make pyruvate and ATP.
How Is Glycolysis Regulated?
• Glycolysis is regulated by feedback
inhibition:
• High levels of ATP (a product of glycolysis)
inhibit the third enzyme:
phosphofructokinase
• Phosphofructokinase has two binding
sites for ATP:
1. When ATP levels are low, it binds to the
active site and the enzyme catalyzes the
third step in glycolysis
2. When ATP levels are high, it binds to a
regulatory site and inhibits the enzyme
During lactic acid fermentation, ATP is made by substrate-level
phosphorylation, indicating that the process involves _____.
A. alcohol production
B. an electron transport chain
C. the transfer of a phosphate group from ATP synthase to ADP
D. the transfer of a phosphate group from a substrate to ADP
Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved
9.3 Processing Pyruvate to Acetyl CoA
• In eukaryotes, pyruvate
produced by glycolysis is
transported into mitochondria
• Mitochondria have inner and
outer membranes
• Cristae are sack-like
compartments formed by the
inner membrane
• The mitochondrial matrix is
inside the inner membrane
Processing Pyruvate to Acetyl CoA
• Pyruvate is processed by pyruvate
dehydrogenase:
• In the mitochondrial matrix in
eukaryotes
• In the cytosol in prokaryotes
• Pyruvate undergoes a series of
reactions:
• One of its carbons is oxidized to CO2
and NADH is produced
• The remaining two-carbon unit is
attached to coenzyme A, producing
acetyl CoA
Processing Pyruvate to Acetyl CoA
• Pyruvate processing is also
regulated by feedback inhibition:
• Pyruvate dehydrogenase is shut
down when it is phosphorylated
• The rate of phosphorylation
increases when levels of NADH,
acetyl CoA, or ATP are high
• Pyruvate dehydrogenase is
dephosphorylated at a higher rate
when levels of ADP, pyruvate, CoA,
or NAD+ are high
9.4 The Citric Acid Cycle: Oxidizing Acetyl CoA
to CO2
• In the citric acid cycle, each acetyl CoA from pyruvate processing is
oxidized into two CO2
• The citric acid cycle is located in the:
• Mitochondrial matrix in eukaryotes
• Cytosol in prokaryotes
• The reactions are organized in a cycle:
• Starts by moving the acetyl group from acetyl CoA
to oxaloacetate to form citrate
• At the end, oxaloacetate is regenerated
The Citric Acid
Cycle Completes
the Oxidation of
Glucose
• Some of the potential
energy released is used to:
1. Reduce three NAD+ to N ADH
2. Reduce one FAD to FADH2
3. Phosphorylate ADP (or GDP)
to form ATP (or GTP)
• The cycle turns twice for
each glucose molecule since
two pyruvate are produced
by glycolysis
Table 9.2 The Reactions of the Citric Acid Cycle
Step Enzyme Reaction
1 Citrate synthase Transfers the 2-carbon acetyl group from acetyl Co A to the 4-carbon molecule oxaloacetate to
produce the 6-carbon molecule citrate.
2 Aconitase Converts citrate to isocitrate by the removal of one water molecule and the addition of
another water molecule.
3 Isocitrate dehydrogenase Oxidizes isocitrate using the N A D+ coenzyme to produce N A D H and release one C O2,
resulting in the formation of the 5-carbon molecule α-ketoglutarate.
4 α-Ketoglutarate Oxidizes α-ketoglutarate using the N A D+ coenzyme to produce N A D H and release one CO2.
dehydrogenase The remaining 4-carbon molecule is added to coenzyme A (C o A) to form succinyl C o A.
5 Succinyl-C o A synthetase Replaces C o A with an inorganic phosphate (Pi), converting succinyl C o A to succinyl
phosphate. This phosphate is then transferred to A D P to form A T P, or to G D P to form G T P,
depending on the version of the enzyme used. What remains after the transfer is succinate.
6 Succinate dehydrogenase Oxidizes succinate by transferring two hydrogens to the coenzyme F A D to produce F A D H2,
resulting in the formation of fumarate.
7 Fumarase Converts fumarate to malate by the addition of one water molecule.
8 Malate dehydrogenase Oxidizes malate by using the N A D+ coenzyme to produce N A D H, resulting in the regeneration
of the oxaloacetate that will be used in step 1 of the cycle.
After the citric acid cycle is complete, the original six
carbons of the glucose molecule are in _____.
A. citric acid
B. oxyloacetate
C. pyruvate
D. carbon dioxide
Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved
The Citric Acid Cycle is Regulated by Feedback
Inhibition
• The citric acid cycle is regulated by
feedback inhibition at multiple
points
• Reaction rates are high when A TP
and NADH are scarce
• Rates are low when A TP or NADH
is abundant
Glucose Oxidation Produces ATP, NADH,
FADH2, and CO2
Free Energy Changes as Glucose is Oxidized
What happens to the released
energy?
9.5 Electron Transport and Chemiosmosis:
Building a Proton Gradient to Produce ATP
• NADH is oxidized when combined with the inner membrane of
mitochondria
• In prokaryotes, its oxidation involves the plasma membrane
• The molecules that oxidize NADH and F ADH2 are called the electron
transport chain (ETC):
• Most are proteins with “helper” groups that are readily reduced or
oxidized
• One is a lipid-soluble, nonprotein called ubiquinone or coenzyme Q or
“Q”
• They have different ability to accept electrons, called their redox
potential
• Some accept only electrons; others accept electrons plus protons
The Electron Transport Chain
• As electrons move from one molecule to
another in the ETC:
• They are held more and more tightly
• A small amount of energy is released in each
reaction
• Each successive bond holds less potential
energy
• The ETC is organized into four protein
complexes, I-IV
• Q and cytochrome c transfer electrons
between complexes
• At the end of the ETC:
• Low-energy electrons are passed to oxygen,
along with protons
• Water is formed
Table 9.3 Components and Reactions of the
Electron Transport Chain
ETC Component Descriptive Name Reaction
Complex one NADH dehydrogenase Oxidizes NADH and transfers the two electrons through proteins containing F MN
prosthetic groups and (Fe·S) cofactors to reduce an oxidized form of ubiquinone (Q).
Four H∙ are pumped out of the matrix to the intermembrane space.
Complex two Succinate dehydrogenase Oxidizes FADH2 and transfers the two electrons through proteins containing (Fe·S)
cofactors to reduce an oxidized form of Q. This complex is also used in step 6 of the
citric acid cycle.
Q Ubiquinone Reduced by two electrons from complexes one or two and moves throughout the
hydrophobic interior of the ETC membrane, where it is oxidized by complex three
Complex three Cytochrome c reductase Oxidizes Q and transfers one electron at a time through proteins containing heme
prosthetic groups and (Fe·S) cofactors to reduce an oxidized form of cytochrome c (cyt
c). A total of four H+ for each pair of electrons is transported from the matrix to the
intermembrane space.
Cyt c Cytochrome c Reduced by accepting a single electron from complex three and moves within the
intermembrane space, where it is oxidized by complex four
Complex four Cytochrome c oxidase Oxidizes cyt c and transfers each electron through proteins containing heme groups.
After two cyt c, will pick up two H+ from the matrix to produce water from oxygen gas
(O2) and pump two additional H+ from the matrix to the intermembrane space.
The Role of the Electron Transport Chain
• The energy from redox
reactions is used to pump
protons from the matrix
into the intermembrane
space
• Most of the chemical
energy from glucose is now
accounted for by a proton
electrochemical gradient
ATP Synthase is Responsible for ATP Synthesis
• In 1960, experiments by Racker
and associates revealed the
protein complex responsible for
ATP synthesis, ATP synthase
• The stalk and knob component of
ATP synthase is essential for ATP
synthesis from ADP and Pi
• The membrane-bound base is a
proton channel
The Chemiosmosis Hypothesis
• In 1961, Mitchell proposed that the
ETC is used to pump protons from
the matrix to the intermembrane
space
• The proton gradient would drive
synthesis of ATP from ADP and Pi—a
process he called chemiosmosis
• ATP production is dependent on a
proton-motive force generated by
the proton electrochemical gradient
The Proton-Motive Force Couples Electron
Transport to ATP Synthesis
• ATP synthase consists of two components:
1. An ATPase “knob” (F1 unit)
2. A membrane-bound, proton-
transporting base (F0 unit)
• The units are connected by a shaft and are
held in place by a stator
• The F0 unit turns as protons flow through it
• The spinning changes the conformation of
the F1 unit so that it phosphorylates ADP to
form ATP
Creating pores in the inner membranes of mitochondria
immediately halts ATP synthesis. The most obvious
explanation accounting for this observation is _____.
A. leakage of hydrogen ions
B. leakage of carbon dioxide
C. leakage of oxygen
D. leakage of ATP
Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved
ATP Yield from Cellular Respiration
• Thus, the energy to produce ATP comes from a proton gradient:
• This process is called oxidative phosphorylation, as opposed to substrate-level phosphorylation
that occurs during glycolysis and the citric acid cycle
• About 29 ATP are produced from each molecule of glucose
• Most of the ATP made during cellular respiration is made by oxidative phosphorylation
Glucose
Metabolism
Organisms Use a Diversity of Electron
Acceptors
• All eukaryotes and many prokaryotes use OXYGEN as the final
electron acceptor for the ETC:
• This is called aerobic respiration
• Using oxygen as the final acceptor provides the greatest energy yield
• It is highly electronegative
• A large difference exists between the potential energy of reduced electron donors and
water
• It allows the generation of a large proton-motive force
• Some prokaryotes use other electron acceptors for the ETC:
• For example, nitrate and sulfate in oxygen-poor environments
• This is called anaerobic respiration
9.6 Fermentation
• What happens when there is no electron acceptor?
• The electrons have no place to go
• The ETC stops
• NADH builds up and there is no NAD+ available to accept electrons:
• Glycolysis, pyruvate processing, and the citric acid cycle stop
• The situation is life threatening
• NAD+ must be regenerated
Fermentation
• Is a metabolic pathway that
regenerates NAD+ from
NADH:
• It includes glycolysis and
additional steps
• Serves as an emergency
backup
• Glycolysis can continue to
produce ATP by substrate-
level phosphorylation in
the absence of oxygen
Many Different Fermentation Pathways Exist
• When our muscle cells cannot
get enough oxygen, they shift to
lactic acid fermentation:
• Pyruvate produced by glycolysis
accepts electrons from NADH
• Lactate and NAD+ are produced
• As muscle cells get more
oxygen, lactate can be
converted back to pyruvate
Many Different Fermentation Pathways Exist
• Some yeast cells can perform
alcohol fermentation:
• Pyruvate is converted to
acetaldehyde and CO2
• Acetaldehyde accepts electrons from
NADH
• Ethanol and NAD+ are produced
• Cells that perform other types of
fermentation are used to make
soy sauce, tofu, yogurt, cheese,
etc.
• Prokaryotes that rely on
fermentation are present in our
intestines
Fermentation as an Alternative to Cellular
Respiration
• Fermentation is much less efficient than cellular respiration
• It produces 2 ATP per glucose, while cellular respiration yields about
29 ATP per glucose
• Some organisms can switch between fermentation and aerobic
respiration:
• Called facultative anaerobes
• They use fermentation only if oxygen is not available
If radioactive sugar were fed to a mouse, the radioactivity
would progress along which of the following paths?
A. sugar to citric acid cycle to pyruvate to carbon dioxide
B. sugar to pyruvate to citric acid cycle to oxygen
C. sugar to citric acid cycle to pyruvate to oxygen
D. sugar to pyruvate to citric acid cycle to carbon dioxide
E. sugar to pyruvate to oxygen to citric acid cycle
Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved
Chapter Summary
• 9.1 An Overview of Cellular Respiration
• Describe the four interconnected processes in cellular respiration and explain their central
role in catabolism and anabolism
• 9.2 Glycolysis: Oxidizing Glucose to Pyruvate
• Describe the process cells use to turn glucose into pyruvate
• 9.3 Processing Pyruvate to Acetyl CoA
• Describe the process cells use to turn pyruvate into acetyl CoA
• 9.4 The Citric Acid Cycle: Oxidizing Acetyl CoA to CO2
• Describe the pathway used by cells to fully oxidize the remaining two carbons from glucose
that are present in acetyl CoA
• 9.5 Electron Transport and Chemiosmosis: Building a Proton Gradient to Produce
ATP
• Analyze the relationship between the electron transport chain and oxidative phosphorylation
• 9.6 Fermentation
• Differentiate cellular respiration and fermentation in terms of inputs, outputs, and ATP
production
Questions? Comments?
Concerns?