CHAPTER 9: CELLULAR RESPIRATION AND FERMENTATION
Chapter 9: Cellular Respiration and Fermentation
Life is Work
 Cells need energy from outside to perform
tasks
 Energy stored in organic molecules of food
comes from the sun and exits as heat 
chemical elements are recycled
 Photosynthesis creates oxygen and organic
molecules that’s used by the mitochondria
for cellular respiration
 Respiration breaks fuel down creating ATP
o CO2 and water = waste which are
raw materials for photosynthesis
9.1 Catabolic pathways yield energy by
oxidizing organic fuels
Catabolic Pathways and Production of ATP
 Organic compounds have potential energy
through arrangement of electrons in bonds
 Fuels = compounds that participate in exergonic reactions
o Enzymes help cells degrade molecules rich in potential energy to use
the energy to use work
 Fermentation = partial degradation of sugars/fuel without use of oxygen
 Cellular respiration = aerobic and anaerobic catabolic pathways
o Aerobic respiration = most efficient, consumes oxygen
 Organic compounds+oxygenCarbon dioxide+water+energy
 Degradation of glucose (exergonic, ∆g = -686 kcal/mol):
C6H12O6 + 6O2  6CO2 + H2O + Energy (ATP + Heat)
o Anaerobic respiration = similar process without oxygen
Redox Reactions: Oxidation and Reduction
 Catabolic pathways yield energy by decomposing fuels by transferring
electrons during chemical reactions, releasing stored energy
 Redox/oxidation-reduction reactions = electron transfers from one reactant
to another: Xe- + Y  X + Y e Oxidation = loss of electrons from a substance
o Electron acceptor (Y) = oxidizing agent (oxidizes Xe- by taking its
electron)
o C6H12O6 (glucose) becomes oxidized
 Reduction = addition of electrons to a substance
o Electron donor (Xe-) = reducing agent (reduces Y by giving it an
electron)
o O2 becomes reduced
 Don’t always involve the complete transfer of electrons- some change degree
of electron sharing in covalent bonds, can partially loose/gain
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o Oxygen is partially reduced in cellular respiration
o The more electronegative an atom, the more energy required to take
an electron away
 Electron loses potential energy when it goes from a less
electronegative to a more electronegative atom
Oxidation of Organic Fuel Molecules During Cellular Respiration
o Molecules with a lot of hydrogen are good fuels because their bonds
are a good source of electrons whose energy can be released as they
fall down an energy gradient when transferred to oxygen
 Hydrogen is transferred from glucose to oxygen  electron
enters a lower energy state releasing energy for ATP synthesis
o Carbs and fats have hydrogen-related energy- only activation energy
barrier holds back flood of electrons to lower energy state
 Enzymes lower activation energy to break down glucose
Stepwise Energy Harvest via NAD+ and the Electron Transport Chain
o Electrons go from: glucose  NADH  ETC  oxygen
o If energy is released from fuel all at once it cant be harnessed for work
 Cellular respiration breaks down glucose in a series of steps
catalyzed by enzymes
o Electrons stripped from glucose, each electron travels with hydrogen
atom which is passed to the coenzyme electron carrier NAD+
 Can easily cycle between oxidized NAD+&reduced NADH states
 Electron acceptor = oxidizing agent
o Dehyrogenase enzymes remove a pair of hydrogen atoms from
substrate, oxidizing it
 Delivers 2 electrons and 1 proton to NAD+
 By receiving only 1 positive ion NAD+’s charge is
neutralized becoming NADH
 Other proton is released as hydrogen ion
o Electrons don’t loose much potential energy when transferred from
glucose to NAD+
 Each NADH represents stored energy that can be used to make
ATP when electrons fall down energy gradient from NADH to
oxygen
o Use electron transport chain to break fall of electrons to oxygen in
many energy releasing steps
 Consists of many molecules/proteins in the inner membrane of
the mitochondria and plasma membrane
 Electrons removed from glucose are shuttled by NADH to the
higher end of the chain, where O2 catches the electrons and H+
at the bottom, forming water
 Electrons loose a little energy with each step until they reach
oxygen = terminal electron acceptor
 Each downhill carrier is more electronegative than the last 
oxygen pulls electrons down the chain
 Electron transfer from NADH  oxygen = exergonic reaction,
∆G = -53
Preview of the Stages of Cellular Respiration
 Harvesting energy from glucose by cellular respiration = accumulation of
glycolysis  pyruvate oxidation and citric acid cycle  oxidative
phosphorylation (ETC and chemiosmosis)
1. Glycolysis occurs in the cytosol and begins the process by breaking
glucose into two molecules of pyruvate
a. Intermediate = pyruvate oxidation into acetyl CoA
2. Citric acid cycle oxidizes
pyruvate using acetyl CoA in
the mitochondria
3. Oxidative phosphorylation
uses the ETC to power ATP
synthesis
 Occurs in the inner
membrane of the
mitochondria
 Makes up 90% of
ATP production
 Substrate-level phosphorylation
creates a smaller amount of ATP
directly in a few glycolysis and citric acid reactions
o Occurs when enzyme transfers phosphate from substrate to ADP
o For each molecule of glucose the cell makes ~32 molecules of ATP,
each with 7.3 kcal/mol of free energy
9.2: Glycolysis harvests chemical energy by oxidizing glucose to pyruvate
Glycolysis means “sugar splitting”
 In glycolysis the 6-carbon sugar glucose is broken into two 3-carbon sugars
o Smaller sugars oxidized, their remaining
atoms becoming pyruvate
 Divided into 2 phases: energy investment and
energy payoff
o In energy investment cell invests 2 ATP
 Phosphate traps glucose in the
cytoplasm
 Lowers activation energy
o In energy payoff the cell repays ATP
investment with interest
 Each G3P gets phosphorylated
twice
 NAD+ is reduced to NADH by
electrons released through the
oxidation of glucose
 Yields 4ATP (2 net) and 2NADH
 All carbon is accounted for in pyruvate, none released as CO2
 Glycolysis occurs whether or not there is O2
o But if there is O2 the chemical energy in pyruvate and NADH can be
extracted by pyruvate oxidation, citric acid cycle, and phosphorylation
 Products: 2 pyruvate, 2 NADH and 2 ATP (net, 4 total)
9.3: After pyruvate is oxidized, the citric acid cycle completes the energyyielding oxidation of organic molecules
Oxidation of Pyruvate to Acetyl CoA (Intermediate phase)
 Products of intermediate phase
o 2 acetate, 2CO2, 2NADH
 If oxygen is present then pyruvate enters a mitochondria via active transport
 Pyruvate is converted into acetyl CoA by a multienzyme complex that
catalyzes 3 reactions:
1. Pyruvate’s oxidized carboxyl group (-COO) is removed and
released as a molecule of CO2
2. Remaining fragment is oxidized forming acetate, extracted
electrons are transferred to NAD+, storing energy in form of NADH
3. Coenzyme A is attached via sulfur atom to acetate forming acetyl
CoA, which has high potential energy
The Citric Acid/Krebs Cycle
 Breaks pyruvate into 3CO2, generating 1ATP per
substrate-level phosphorylation
 Most of chemical energy is transferred to NAD+
and coenzyme FAD
 Reduced NADH and FADH2 shuttle high energy
electrons to ETC
 Cycle has 8 steps, each catalyzed by an enzyme
 Energy molecules produced:
o Acetyl group of acetyl CoA joins cycle by
combining with oxaloacetate forming
citrate (1)
 Rest of steps decompose citrate
back to oxaloacetate (cycle)
o Each acetyl group that enters cycle, 3NAD+
reduced to NADH (3, 4, 8)
o Electrons are transferred to FAD becoming
FAD2 (6)
o Substrate-level phosphorylation produces GTP which can be used to
make ATP or act like ATP to power work (5)
 Some form ATP directly (only ATP in citric acid cycle)
9.4: During oxidative phosphorylation, chemiosmosis couples electron
transport to ATP synthesis
The Pathway of Electron Transport
 Electron transport chain = collection of molecules embedded in the inner
mitochondrial membrane in eukaryotes (plasma membrane in prokaryotes)
o Cristae increases surface area providing space for more chain
 Most molecules are proteins
o Nonprotein prosthetic groups bound, essential for enzyme function
 Electrons removed from glucose by NAD+ (during glycolysis + citric acid
cycle) are transferred from NADH to flavoprotein (1st molecule of ETC) in
complex 1
o As it returns to oxidized form it passes electrons to iron-sulfur protein
 Passes electrons to ubiquinone (only nonprotein)
 Cytochromes = proteins, remaining electron carriers
before oxygen
o Heme group accepts electrons
o Oxygen = very electronegative, accepts electrons
and pair of hydrogen ions

FADH2 also adds electrons to the ETC
o Adds at complex 2 = lower energy level than
NADH  while NADH and FADH2 add same
number of electrons, FADH provides 1/3
less energy than NADH
 ETC doesn’t make ATP directly- instead the
electrons break a large free-energy drop into
smaller steps releasing manageable amounts
Chemiosmosis: The Energy-Coupling Mechanism
 Chemiosmosis = process uses energy stored in the
form of a hydrogen ion gradient to drive ATP
synthesis
 ATP synthase = enzyme that actually makes ATP
from ADP and P
o Works like an ion pump in reverse
o Uses energy of an ion gradient for power
 Power source = difference in concentration
gradient of H+ (or difference in pH) on either side of the mitochondrial
membrane
o Creating H+ gradient = function of ETC
o Uses flow of electrons to pump H+ across
the membrane from mitochondrial matrix
 intermembrane space
o H+ wants to diffuse back, ATP synthase
provides only route out
 ATP synthase is a multisubunit complex with 4
main parts made of multiple polypeptides
o Uses exergonic flow of H+ to drive
phosphorylation
o Protons move one by one into binding
sites on the rotor, causing it to spin,
catalyzing ATP production from ADP and P
 Certain parts of the ETC accept and release
protons (H+) along with electrons
o Electron transfers cause H+ to be taken up
and released into surrounding solution
o Arranged in a way that H+ is accepted
from mitochondrial matrix and deposited
into intermembrane space
o Resulting H+ gradient with capacity to
perform work = proton-motive force 
drives H+ back across membrane through
H+ channels provided by ATP synthases
 Chemiosmosis occurs in elsewhere in other
variations
o Chloroplasts use to generate ATP, where light drives electron flow and
H+ gradient formation
o Prokaryotes use in plasma membranes to rotate flagella, pump waste
An Accounting of ATP Production by Cellular Respiration
 Energy flow in respiration: glucose  NADH  ETC  proton-motive force
 ATP
 Departments of metabolic process= glycolysis, inter, citric acid cycle, and ETC
o 4 ATP created in substrate-level phosphorylation in glycolysis and
citric acid cycle
o Much more ATP created in oxidative phosphorylation (each NADH
that transfers a pair of electrons generates ~30 ATP)
 Why are numbers of ATP inexact?
o Phosphorylation and redox reactions aren’t coupled so ratio of
number of NADH to ATP is not a whole number
 1 NADH transports 10H+, 4H+ generate 1 ATP  1 NADH
generates 2.5 ATP
 Since FADH2 enters later, it only moves enough H+ to generate
1.5 ATP
o ATP yield varies depending on type of shuttle used to transport
electrons from cytosol to mitochondrion
 NAD+ shuttle yields more ATP than FAD
o Proton-motive force is used to drive other kinds of work (powers
uptake of pyruvate from cytosol)
 Efficiency of respiration:
o Complete oxidation releases 686 kcal per mol
o Phosphorylation of ADP  ATP stores 7.3 per ATP
o (7.3*32 ATP)/686 = .34  34% of potential chemical energy in
glucose is transferred to ATP = efficient
Rest of the energy stored in glucose is lost to heat (we use
some to maintain body temp, dissipate rest through sweat)
o Sometimes beneficial to reduce efficiency
 Hibernating mammals winter in state of inactivity: ongoing
oxidation of stored fuel, generating body heat without ATP
production

9.5: Fermentation and anaerobic respiration enable cells to produce ATP
without the use of oxygen
ATP generation without oxygen?!
 Without the electronegative oxygen to pull electrons down the ETC, oxidative
phosphorylation would stop
 Anaerobic respiration uses ETC
o Takes place in prokaryotic organisms that live without oxygen
o Use other, less electronegative substances as final electron acceptors
 Fermentation harvests chemical energy without cellular respiration (oxygen
or an ETC)
o Consists of glycolysis + reactions to regenerate NAD+ by transferring
electrons from NADH to pyruvate, which is reused to oxidize sugar by
glycolysis, creating 2ATP by substrate-level phosphorylation
o Glycolysis generates 2ATP without oxygen present
o Fermentation extends glycolysis by allowing continuous generation of
ATP through substrate-level phosphorylation of glycolysis
o Needs sufficient supply of NAD+ to accept electrons during oxidation
 Instead of transferring electrons to ETC to recycle NAD+ from
NADH fermentation transfers electrons from NADH pyruvate
Types of Fermentation
 Alcohol fermentation
o Converts pyruvate to ethanol
 Releases CO2 from pyruvate, converting
it to acetaldehyde
 NADH reduces acetaldehyde to ethanol,
regenerating NAD+
o Bacteria and yeast do alcohol fermentation
 CO2 bubbles released allow bread to rise
 Lactic acid fermentation:
o NADH directly reduces pyruvate, forming
lactate as an end product and not releasing
CO2
o Muscle cells do when oxygen is scarce (early
stages of exercise when sugar catabolism for
ATP outpaces muscle’s supply of oxygen)
 Lactate that accumulates goes to liver to
be converted back to pyruvate to be used
in the mitochondria
o Used by fungi and bacteria to make cheese and yogurt
Comparing Fermentation with Anaerobic and Aerobic Respiration
 All use…
o Pathways for producing ATP by harvesting chemical energy from food
o Glycolysis to oxidize glucose into pyruvate producing 2ATP through
substrate-level phosphorylation
o NAD+ as oxidizing agent to accept electrons from food during
glycolysis
 Mechanism for oxidizing NADH back to NAD+ is different
 Different final electron acceptors:
o Fermentation = pyruvate or acetaldehyde
o Aerobic respiration = oxygen
o Anaerobic respiration = a different electronegative molecule
 Respiration harvests much more ATP because it harnesses energy stored
pyruvate by oxidizing it using ETC
o Aerobic respiration yields 16x more ATP than fermentation
 Obligate anaerobes carry out only fermentation or anaerobic respiration
o Can’t survive in the presence of oxygen (toxic)
 Facultative anaerobes can survive using fermentation
or respiration
o To make same amount of ATP it has to
consume sugar at a much faster rate when
fermenting than when respiring
o Human muscle cells
 Some cell types can only carry out aerobic oxidation
(brain cells)
9.6: Glycolysis and citric acid cycle connect to many other metabolic pathways
The Versatility of Catabolism
 Free glucose molecules = uncommon- get
most of calories from fats, proteins,
sucrose, and starch
o Organic molecules in food can be
used by respiration to make ATP
 Glycolysis can accept a wide range of carbs
for catabolism
o Starch, glycogen, and sucrose can
be hydrolyzed into glucose
 Proteins can must be digested into amino
acids before being used as fuel
o Used to build new proteins
o Enzymes convert excess amino
acids into intermediates of
glycolysis and citric acid cycle
 First their amino groups are
removed = deamination
 Can harvest energy from fats from food or
storage
o After fats are digested to glycerol
and fatty acids glycerol is converted
to glyceraldehyde 3-phosphate =
intermediate of glycolysis
o Beta oxidation breaks fatty acids into two-carbon fragments which
enter krebs cycle as acetyl CoA
 Most of energy of a fat is stored in fatty acids
 Generates NADH and FADH2 which enter ETC
o Fats make good fuel because of their chemical structure and high
energy level of electrons (compared to carbs)
 Gram of fat oxidized produces more than twice a carb
Biosynthesis/Anabolic Pathways
 Food also provides carbon skeletons that cells need to make molecules
o Some monomers can be used directly
 If the body needs molecules not found in food glycolysis and citric acid cycle
intermediates can be diverted into anabolic pathways as precursors for the
sell to synthesize molecules
o Consume rather than generate ATP
 Glycolysis and citric acid cycle function as metabolic interchanges that allow
cells to convert some molecules to others
o If we eat more food than necessary we store fat
Regulation of Cellular Respiration via Feedback Mechanisms
 Supply and demand regulates metabolism
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Feedback inhibition: when the end product of an anabolic pathway inhibits
the enzyme that catalyzes an early step of the pathway
Controls catabolism by regulating enzyme activity in pathway
If ATP concentration drops, respiration speeds up
When there is too much ATP, respiration slows down
Phosphofructokinase = important switch- enzyme that catalyzes step 3 of
glycolysis  can speed up or slow down entire process
o Allosteric enzyme: inhibited by ATP and stimulated by AMP
o As ATP accumulates, inhibition slows glycolysis
o If citrate accumulates in mitochondria, some passes to the cytosol 
inhibits phosphofructokinase  decreases supply of acetyl to CAC
 Works the other way if citrate consumption increases
 Synchronizes rates of glycolysis and citric acid cycle
Class notes:
Two ways to make ATP
 Substrate level Phosphorylation makes 4 ATP
o Compound + P  ADP  ATP
 Oxidative Phosphorylation makes 30ish ATP (kills it!)
o Gradient with membrane potential- relieve membrane potential and
use that energy to make ATP
o ATP synthase keeps membrane door shut to accumulate H+ to build
gradient, H+ is so ready to leave that once it opens they all rush out 
uses energy of H+ rushing to make ATP from ADP and P = electron
transport chain
o Proteins embedded in membrane, each more electronegative than the
next so electrons jump down proteins  energy of them jumping is
used to pump H+ in, powering gradient
 Electrons come from carbohydrates
 NAD+ and FAD+ = coenzymes, oxidizing agents, represent
stored energy that is tapped to synthesize ATP
 Take hydrogen and electrons from other places and
bring them to site of oxidative phosphorylation
 NADH carries energy to make 3ATP because it deposits
its electrons at the first protein
 FADH carries energy to make 2ATP because it deposits
its electrons at the second protein
 Glycolysis (2 NADH)  intermediate step (2NADH)  Krebs (6NADH,
2AFOH)  ETC
Product
NADH
FADH2
CO2
ADP
ATP
(substrate
level)
ATP
(oxidative)
Glycolysis
2
0
0
2
4
Inter
2
0
2
0
0
Citric Acid
6
2
4
0
2
ETC
0
0
0
0
0
Total
10
2
6
2
6-2 = 4
0
0
0
34
34