SimUTtext 2020-2021

Section 1: Cellular respiration: food, breath, exercise

Cells use the energy stores in the food you eat to make ATP, which powers essential cellular
processes
Section 2: The electron transport chain (ETC)
The electron transport chain uses the energy stored in molecules such as NADH to charge a
battery that is used to make ATP from ADP and phosphate

SECTION 1
Fueling life’s work: 1
All of the work we do, from pedalling a bicycle to typing on a keyboard, requires energy, and
the source of that energy is the food we eat. But how do our bodies convert the energy stored
in the food we eat to the energy we use to function? A critical part of the answer lies in
molecules called Adenosine Triphosphate, or ATP, the cell’s energy “currency”. Without
sufficient ATP, we would be unable to breathe, move, or think.
This module explores how energy is stored and processed by cells, focusing in particular on the
elegant system our mitochondria use to transfer energy into ATP molecules. This process is so
central to life that it occurs very similarly in all animals, plants, and eukaryotes. Because the
transformation usually involves oxygen and carbon dioxide, it is called cellular respiration.
Adenosine Triphosphate: ATP is a molecule used in cells that stores and provides energy
used for many cellular processes. ATP gets its name from the three (“tri”) phosphate groups
it contains. ATP is converted into Adenosine diphosphate (ADP) by giving up one of its
phosphate groups, releasing energy that is then harnessed by the cell for work. In the
reverse process, ADP can combine with a phosphate group to make ATP, which requires
energy.
Adenosine Diphosphate: ADP is a molecule involved with energy transfer for many cellular
functions. ADP gets its name from the two (“di”) phosphate groups it contains. ADP can
combine with a phosphate group to make adenosine triphosphate (ATP), in a process that
requires energy. Later, ATP converts to ADP by giving up a phosphate group, releasing energy
that is used by the cell to do work.
Cellular Respiration: Cellular respiration is the process of breaking down glucose and other
food molecules into smaller pieces and using the energy released from these reactions to
generate ATP using an electron transport chain.
Eukaryotic Cell: A eukaryotic cell contains structures enclosed in membranes. All Eukaryotic
cells have a membrane-bound nucleus. The mitochondrion is another membrane-bound
organelle found in many eukaryotic cells.
Mitochondrion: A mitochondria is the organelle that produces most of the ATP generated from
cellular respiration when oxygen is present. Each mitochondrion is surrounded by an inner and
outer membrane. The matrix is surrounded by the mitochondrial inner membrane, while the
intermembrane space lies between the inner and outer mitochondrial membranes. Pyruvate
processing and the citric acid cycle occur in the mitochondrial matrix. The electron transport
chain and ATP synthase are located in the mitochondrial inner membrane.
Exercise and Respiration: 2
One activity that makes us very aware of respiration is exercising. The woman on the right is a
cyclist who’s decided to enter her first road race. She had recently started an ambitious training
program that requires discipline and a lot of exercise. She has had a good lunch and is now out
for an afternoon ride.
As the speed of the cyclist increases, the more glucose and oxygen she uses, and the more
carbon dioxide is produced.
When she is not pedaling, glucose is still being used. In order to perform essential activity in
your heart, lungs, and brain, to keep you alive, glucose is always being used.
Glucose: a sugar with six carbon atoms (6 C) and is an energy source for cellular respiration
Oxygen: refer to an oxygen atom, or the gas, O2. Oxygen is consumed by the electron transport
chain and is required for it to function.
Carbon Dioxide: a molecule consisting of one carbon atom bonded to two oxygen atoms.
Carbon dioxide is a product of cellular respiration.

Energy is stored and converted: 3

Doing work, such as pedalling a bike, requires energy. When our bodies need energy, the
energy in glucose is used to make ATP. Our bodies can also transfer energy from fats to ATP.
It is easy to verify that glucose stores energy. One way is to light it on fire. When burning,
glucose combines with oxygen to produce carbon dioxide and water vapour, while releasing
energy in the form of heat and light. This chemical reaction is:
Glucose + 6 O2  6 CO2 + 6 H2O + energy

This is the overall reaction that takes place during cellular respiration
The cyclist’s cells use the same overall reaction to transfer energy from glucose. But instead of
generating heat and light, the cyclist captures that energy in molecules of ATP. Capturing the
energy requires cellular respiration, which involves a sequence of reactions.
Energy can be converted between forms: 4
The idea that energy can be transferred from one entity (glucose) to another (ATP) is central to
understanding respiration. This module uses two conventions, shown in the animation to the
right, to help illustrate energy transfer.
First, components that are higher up on the page have higher potential energy.
Potential energy: stored energy that can be converted to work or to other forms of energy
Second, compressed springs represent high potential energy, while relaxed springs represent
low potential energy. The ball on the right is initially elevated, indicating high potential (stored)
energy. The spring is not compressed, indicating low potential energy.
As the ball falls down to lower potential energy, its energy is transferred to the spring, which
then becomes compressed. This energy transfer is mediated by the seesaw, which later on, will
represent biological enzymes.
Enzymes: molecules (usually proteins) that can increase the rate of a chemical reaction
Note that the ball’s potential energy could have bene used to conduct work instead of being
transferred to the spring. In cells, the potential energy stored in ATp is often used to perform
work.

In the reaction, Glucose + 6 O2  6 CO2 + 6 H2O + energy

Glucose has more potential energy

Storing energy in ATP: 5

How is potential energy “stored” in a molecule?
The chemical structure of ATP is illustrated. ATP stands for adenosine triphosphate because it
has three phosphate groups (orange circles). Each phosphate group is made of a phosphorous
atom covalently bonded to several oxygen atoms. If you look closely, you’ll notice negative
charges on some of the oxygen atoms. Because like charges repel, these negative oxygen
molecules electrically repel each other. When phosphate groups are bonded close together, it’s
like compressing a spring, due to their inherent repulsion.
Phosphate groups: Phosphate is a chemical composed of a phosphorus atom covalently
bonded to 4 oxygen atoms. In cellular environments, phosphate is negatively charged.
Phosphate can be joined with ADP to make ATP, in a process that requires energy. Phosphate is
also called inorganic phosphate.
Covalent Bond: in a molecule, a covalent bond holds atoms together via the sharing of
electrons.
Electrons: negatively charged particles in atoms. They are involved in covalent bonds when
shared between atoms.
The second panel shows a simplified ATP molecule. Note the bonds (latches) between
phosphate groups (labelled Pi, the symbol for inorganic phosphate) where potential energy is
stored (represented as compressed springs)
After the bond breaks (via hydrolysis) repulsion between the negative oxygen atoms splits ATP
into ADP and a phosphate while releasing the stored energy.

Hydrolysis: The process of breaking a covalent bond through the addition of a water molecule.
The conversion of ATP into ADP and phosphate is an example of hydrolysis.
The conversion of ATP into ADP releases stored potential energy.

Glucose stores a lot of energy: 6! She went 0.9km on one sugar cube!

Overall energetics of respiration: 7

A single molecule of glucose itself is quite energy-rich compared to a single molecule of ATP. As
shown in the animation, respiration can produce about 30 molecules of ATP from one glucose
molecules (the exact number varies with cell conditions)
Glucose falls down to lower Ep, becoming Carbon dioxide and water, while the phosphate is
lifted up, combining with ADP to form high, energy ATP!
Note, the cells use the energy stored in glucose to make ATP from ADP and phosphate. Glucose
is not converted into energy, but the energy stored in it is used to make ATP.

Cellular respiration overview: 8

Cellular respiration involves many steps, summarized in the diagram below. On the next page
you will watch a video explaining the four major processes, called (in order) glycolysis, pyruvate
processing, the citric acid cycle, and the electron transport chain.

Pay attention to where each of the following molecules are created and used:
- ATP: the ultimate product of respiration is ATP
- NADH and FADH2: in cellular respiration, these two molecules serve as carriers of
potential energy, via their electrons. They store less energy than glucose, but more than
ATP
- CO2: the carbon atoms in glucose are eventually incorporate into carbon dioxide
molecules.
- O2: as you’ll see later, oxygen is required for an organism to make maximum use of the
energy in glucose.
NADH: Nicotinamide adenine dinucleotide (NAD+) is an electron carrier molecule. In cellular
respiration, the role of NAD+ is to transfer high-energy electrons to the electron transport
chain, where that energy can be used to make ATP. In glycolysis, pyruvate processing, and the
citric acid cycle, NAD+ is reduced to NADH as it gains two electrons and two protons. NADH can
be oxidized back to NAD+ by transferring its electrons to Complex I in the electron transport
chain.
FADH2: Flavin Adenine Dinucleotide (FAD) is an electron carrier molecule. In cellular
respiration, the role of FAD is to transfer high energy electrons to the electron transport chain,
where that energy can be used to make ATP. FAD can be reduced to FADH2 in the citric acid
cycle, where it gains two electrons and two protons. FADH2 can be oxidized back to FAD (plus 2
protons) by transferring its electrons to Complex II.
Reduction-oxidation reaction (redox): redox reactions are chemical reactions where electrons
are transferred between molecules or atoms. In such reactions, one atom or molecule is
oxidized while the other is reduced. In REDUCTION, electrons move towards the atom or
molecule. In OXIDATION, electrons move away from the atom or molecule.

Video: 9
Cells are powered by the energy made available by cellular respiration.
In this process ATP is generated from energy stored in glucose. Glucose has six carbon atoms
represented by these yellow dots. The first step is glycolysis which occurs in the cytoplasm and
converts glucose into two molecules of pyruvate. Potential energy released in this process is
captured by forming two ATP molecules and two NADH molecules. Next is pyruvate processing,
pyruvate molecules move into the mitochondria where each release one carbon atom as
carbon dioxide- the remaining 2 carbon atoms from each pyruvate are incorporated into acetyl
coenzyme a also called acetyl CoA. Potential energy released in this process is transferred to
two NADH molecules.
Next acetyl Co a enters the citric acid cycle. There the two molecules of acetyl CoA release 4
carbon dioxide molecules. At this point all six carbon atoms from the glucose molecule are in
carbon dioxide molecules. Within the citric acid cycle the energy released during molecular
transformations is transferred to 2 ATP, 6 NADH, and two FADH2 molecules.
So far the energy from glucose has been used to make a total of four ATP but also notice that
many molecules of NADH and FADH2 have been made.
In the final step the energy that has previously been stored in molecules of NADH and FADH2 is
used in the electron transport chain to generate 25 to 30 more ATP molecules. Oxygen is
required for this process and is incorporated into water. Overall the cell makes about 30 ATP
molecules from the energy stored in the bonds of a single glucose molecule. Along the way the
six carbon atoms in glucose have been incorporated into six molecules of carbon dioxide.

Questions: 10
- THE ELECTRON TRANSPORT CHAIN (more specifically, ATP synthase) MAKES MOST OF
THE CELL’S ATP.
- PYRUVATE PROCESSING AND THE CITRIC ACID CYCLE PRODCUE CARBON DIOXIDE
- THE ELECTRON TRANSPORT CHAIN USES OXYGEN.

Questions: 11
Oxygen is a key ingredient in cellular respiration. That’s why the cyclist breathes more heavily
when pedaling faster.

Questions: 12
If the cyclist had decreased oxygen availability, she will still use glucose for energy, but without
oxygen, her body gets much less energy out of this glucose. This means that she will not
produce as much CO2, as well as she cannot pedal as fast.
The role of oxygen in cellular respiration is it allows the cyclist to go farther on less glucose.

Oxygen affinity for electrons: 13

Oxygen has a strong affinity for electrons, and this is one of the reasons that oxygen is so
important for cellular respiration. When two atoms are attached with a covalent bond,
electrons are shared between atoms. In the diagram, you can see one of the carbon atoms in a
glucose molecule. Because carbon (c) and hydrogen (h) have an equal affinity for electrons, the
electrons are, on average, near the centre of each bond. The (partial) glucose molecule
depicted is going to react with the oxygen atom.

Notice that oxygen must have a higher affinity for electrons than hydrogen does, because the
bottom 2 electrons end up closer to the OH group than they were to the hydrogen before the
reaction. Oxygen has a stronger affinity for electrons than does either carbon or hydrogen.

After the rection with oxygen, the electrons shift so that they are closer to oxygen than they are
to carbon, due to oxygen’s pull on them. Importantly, this shift reduces the potential energy of
the molecule. Because the potential energy is decreasing, energy is released; cells use this
energy to produce ATP.
In general, when electrons in a bond are more tightly held to an atom, as exemplified by their
proximity to oxygens nucleus, the less potential energy is in the bond.
NOTE: this useful generalization disguises some complex chemistry that lies beyond the scope
of this module.

Redox: 14
Because oxygen has an especially strong pull on electrons compared to other atoms, when a
molecule like glucose reacts with oxygen, chemists say that the molecule was oxidized. An atom
or molecule is oxidized when it loses an electron (or its shared electrons move away from it),
although this doesn’t necessarily require oxygen. Because electrons moving away from one
atom must move toward another, there is always a corresponding atom or molecule that gains
electrons. Chemists say that the atom gaining electrons has been reduced. This, the oxygen in
the scenario on the previous page has been reduced upon reacting with glucose.
Because reduction and oxidation always occur together, they are often referred to as redox
reactions (short for reduction-oxidation).
Plants are capable of taking CO2 from the air around them and using the carbon to produce
glucose, in a process that is the reverse of respiration. In this process is carbon oxidized or
reduced? Carbon is reduced!
- electrons in this reverse reaction (part of the process of photosynthesis) will move away from
the oxygen toward the carbon, the opposite of what happens to the carbon-based molecule in
the diagram above.

Redox Continued: 15
Redox reactions do not always involved oxygen. Any reaction where electrons are transferred
from one atom to another is called a redox reaction. These occur throughout cellular
respiration. You have seen that when carbon atoms from glucose are oxidized, electrons are
closer to oxygen, and energy is released. How do cells capture this energy?
To demonstrate, the animation shows on carbon atom within a molecule derived from glucose
on the left side, and an NAD+ molecule plus a free hydrogen ion (H+) on the right. NAD+ is used
during respiration to store and transfer high energy through redox reactions.
WHEN NAD+ and H+ are converted into NADH, NAD+ is reduced to form NADH. Because
oxidation and reduction occur together, this means that the carbon on the left hand size is
oxidized.


When NAD+ and H_ are converted to NADH, energy is transferred from glucose to NADH.

During glycolosis, pyruvate processing, and the citric acid cycle, cells use energy released from
the oxidation of glucose to push high-energy electrons onto NAD+ and FAD, making NADH and
FADH2. These molecules then shuffle the high-energy electrons to the electron tranpsort chain,
which harnesses the energy to product a large amount of the ATP used by cells.

Consequence of exercise: 16
When your bodu uses glucose for energy during exercise, you weigh less afterwards, why?
Because glucose is transformed into carbon dioxide and water that is lost through exhaling and
sweat.
Glucose and oxygen are converted into CO2 and H2O during respiration. The chemical products
have the same mass as the reactants, but during exercise, CO2 is exhaled and we lose
additional mass through evaporation of sweat from the skin. Cells do not convert molecules
directly into energy but rather transfer the energy to different molecules.

Section summary: 17
- Cells need energy to function
- Energy is stored in molecules such as glucose and ATP
- ATP is the energy currency of the cell. Its hydrolysis to ADP releases energy used to
power cellular processes.
- Cellular respiration is the process of breaking down glucose and other foods and using
the released energy to generate ATP by means of an electron transport chain.
- Cellular respiration involves four major processes: glycolysis, pyruvate processing, the
citric acid cycle, and the electron transport chain.
- Energy can be transferred from one place to another and converted between potential
energy and work.
- Reactions that transfer electrons are called redox reactions. A redox reaction always has
one atom or molecule that is oxidized and one that is reduced
- Cellular respiration uses oxygen to oxidize glucose which allows the cell to extract more
energy from glucose
- There are many redox reactions throughout cellular respiration. Among the most
important are those involving the electron carrier NAD+, which is reduced to NADH
during glycolysis, pyruvate processing, and the citric acid cycle, and oxidized back to
NAD+ by the electron transport chain.

Questions: 18
The potential energy in glucose, like potential energy in any molecule or object, can be used to
do work or can be converted to other forms energy that are used to do work.
Energy stored in ATP is used to work during muscle contractions
To enhance performance in a long-distance race, as racing speed is primarily limited by how
much oxygen can be delivered to the muscles, we can increase the amount of red blood cells in
the blood to allow the blood to carry more oxygen than before. Without enough oxygen, cells
produce far less ATP from glucose.
If the sweetener could not be used to make ATP, the person would have to make ATP from
other foods or from stored fats. If the sweetener still made the person feel like they had a full
stomach, they would not have to each as much real food overall, causing a person to lose
weight.
SECTION 2
Mitochondria and the ETC: 1
The previous section provided an overview of the processes involved in cellular respiration. This
section probes more deeply into the inner workings of the cool but complicated electron
transport chain (ETC). As its name implies, the ETC involves the transport of electrons. The
primary links in the chain are protein complexes, and the transport of electrons occurs via a
sequence of redox reactions involving those complexes. Importantly, the ETC connects the
transfer of electrons to the movement of protons, which, as you will see, ultimately enables
cells to produce the all-important ATP.
Electron Transport Chain: the mitochondrial electron transport chain is a set of proteins and
other molecules that moves protons (H+ ions) from the matrix into the intermembrane space.
This is accomplished by a series of reactions in which electrons from NADH or FADH2 are
ultimately passed to oxygen atoms. The term “electron transport chain” refers to both the set
of molecules and the overall process of successive redox reactions and proton pumping that
ultimately lead to the production of ATP.
The electron transport chain is located in the mitochondria of eukaryotic cells and, when
oxygen is available, the ETC contributes to most of the ATP production during cellular
respiration. This section explores how the ETC performs its role in cellular respiration and how
nature and drugs can modify it to work differently.

A magic diet drug? : 2

Recall that the cyclist n this module is training for a race. She is paying close attention to her
weight in order to reduce her body fat percentage, because she knows that her performance in
the race will be affected by her strength to weight ratio.
For this, and other purposes, the pharmaceutical industry dreams of a drug that could help
people shed pounds, even without exercise. Remarkably, a drug like this exists. It’s called
dinitrophenol (DNP) and was once marketed as a weight loss pill. Unfortunately, side effects
include fatigue, hyperthermia, and sometimes death – the drug’s effective dose is very close to
the lethal dose.
- DNP causes greater glucose and oxygen usage, and more CO2 exhaled, regardless of the
cyclist’s speed.

Where are the mitochondria? : 3

Most of the cells in your body have mitochondria, and cells that use a lot of ATP (such as muscle
cells) usually have the most mitochondria. As you can see, the mitochondria in a muscle are
distributed throughout the cell so that ATP is generated close to each of the myofibrils (the rod-
shaped units in a muscle fibre) where it is used.
To make ATP, the mitochondria need a source of potential energy. Recall from the previous
section that glycolysis, pyruvate processing, and the citric acid cycle produce only a few ATP
molecules per glucose molecule. These earlier steps in respiration also produce several
molecules of NADH and FADH2 per glucose molecules. NADH and FADH2 store potential energy
and carry it to the electron transport chain (ETC).

Meet the ETC players: 4

The image zooms in on the mitochondrial membranes. Notice that the mitochondrion has two
cell membranes. Within the inner membrane is a set of protein complexes located between the
mitochondrial matrix (the interior of the organelle) and the intermembrane space (between the
inner and outer membranes).
Inner membrane: the mitochondrial inner membrane is the inner of the two membranes
surrounding each mitochondrion and is the boundary between the matrix and intermembrane
space
Protein Complexes: a protein complex is a group of multiple proteins bound together
Mitochondrial Matrix: the mitochondrial matrix comprises the inside of the mitochondrial
inner membrane that surrounds each mitochondrion. This matrix is the location of pyruvate
processing and the citric acid cycle.
Intermembrane Space: the mitochondrial intermembrane space is the volume between the
inner and outer mitochondrial membranes that surround each mitochondrion.
The protein complexes of the electron transport chain include four membrane-bound
complexes named, Complex I through complex IV. Additionally, there are two smaller molecules
named coenzyme Q and cytochrome c (abbreviated Q and Cyt c). The term “electron transport
chain” refers not only to this entire group of molecules but also to the process they undertake.
The name “electron transport chain” is derived from the transfer of electrons from NADH or
FADH2 to oxygen. This transfer drives the energetic changes that ultimately produce ATP.
Another important protein in the mitochondrial membrane is ATP synthase, shown at the far
right. This protein uses energy generated by the ETC to combine ADP and phosphate together,
producing ATP.
ATP synthase: An enzyme that cells use to make ATP from ADP and a phosphate group. In
mitochondria, ATP synthase is located in the inner mitochondrial membrane and makes ATP
using the energy from protons (H+ ions) moving from the intermembrane space into the
mitochondrial matrix.

Overview of the ETC: 5

The simulation of the electron transport chain on the right provides an overview of how the ETC
works. The process is pretty involved, but do not worry about the details just yet. Try to see the
big picture. Note that there are two electrons (each with a little gray circle with a minus sign)
attached to the NADH molecule beneath the ETC. You can also find protons, shown either as
white circles with + signs or as hydrogen ions (H+) when occurring with other molecules.
Video:
And how energy that is stored in NADH is used to make most of the ATP cells get from glucose
when oxygen is present. As you've seen molecules of NADH are produced during respiration.
NADH shuttles high energy electrons to the electron transport chain. Energy is represented in
this compressed spring (of NADH) this energy is ultimately used to make ATP. Note in this
simulation, energy is represented by height higher up means higher energy. The process starts
with NADH giving its electrons to complex one this- results in the injection of high energy
electrons into complex one. Here the ETC is simulated as a marble run- watch as the electrons
roll down the marble run toward lower potential energy. Focus on moving electrons protons
and ATP. If things happen too quickly or slowly adjust the speed slider. Notice that the electrons
fall down to lower potential energy, which is coupled to the pumping of protons upward to
where they have higher potential energy. This is accomplished by some of the ETC complexes.
When electrons are at their lowest energy they are transferred to oxygen. A pair of hydrogen
ions is added to make water H2O, notice the protons that have been lifted into the
intermembrane space- due to the high concentration of positive charge here and the fact that
like charges repel protons, are repelled from this region and attracted to the matrix. Thus
protons in the intermembrane space have high potential energy. ATP synthase allows the
protons to re-enter the matrix as they do so they fall to lower potential energy. The energy they
release is used to make ATP from ADP. If you wish to see the simulation again press the reset
button to start over. As you've seen NADH carries high energy electrons to the electron
transport chain. The ETC creates a proton gradient- the energy from which is used by ATP
synthase to make ATP. On the following pages you can see in more detail how this occurs. The
key idea is the transfer of potential energy from electrons and NADH to protons in the
intermembrane space and ultimately to ATP.

NOTE NADH is oxidized and complex I is reduced. Since electrons leave NADH, NADH is
oxidized, and Complex I is reduced because it gains electrons.

Notice that protons move into the intermembrane space. This movement is powered by the
redox reactions that occur as electrons move from one complex to the next.
Imagine a toy with a ramp, down which you roll marbles. The red line on the right represents an
imaginary marble run for electrons. In the ETC’s electron run, the ramp represents potential
energy of electrons.

As electrons decrease in potential energy as they move through the ETC.

Charging the battery: 6
Because like charged repel on another, the process of concentrating protons into a confined
space requires an input of energy. For example, if you have ever used rechargeable batteries,
you know it requires energy to charge them. Like rechargeable batteries, mitochondria store
and then release potential energy via the concentration of like charges.
As you will see, pumping protons out of the mitochondrial matrix into the intermembrane
space is the key to how energy is stored and released in eukaryotic cells.
What do you notice about moving protons into the intermembrane space?
Notice that as more protons are moved, you have to drag the protons farther with your mouse
to see the proton cross the membrane (similar to when you were dragging phosphate onto ADP
in the last section). Energy is required to move additional protons across the membrane.
Why is it harder to move each additional proton into the intermembrane space?
As more protons are moved into the intermembrane space, it becomes electrically positive,
which will repel additional protons from this area.

ATP synthase uses the proton gradient: 7

The ETC pumps protons from the mitochondrial matrix into the intermembrane space. This
results in a proton gradient, with many more protons in the intermembrane space than in the
mitochondrial matrix. The subsequent repulsion among positively charged protons in the
intermembrane space, as well as the attraction of protons to the more negatively charged
mitochondrial matrix, propels protons to move across to the matrix. This propulsion is an active
process, mediated by electrical forces. In addition, passive diffusion of protons for the
intermembrane space, where they are highly concentrated, into the mitochondrial matrix,
where they are also sparce, occurs.
Gradient: a chemical gradient occurs when there is a difference in the concentration of the
substance in different locations
Diffusion: Molecules are in constant, random motion. When there is a difference in the
concentration of a type of molecule from one location to another, this random movement
results in a net movement of molecules from the region of higher concentration to lower
concentration. This process, diffusion, is the net movement of a substance from a region of
higher concentration to a region of lower concentration.
Thus, the ETC stores potential energy by pumping protons into the intermembrane space,
creating a proton gradient. Protons are powerfully repelled from the intermembrane space, and
enormous energy can be released when they move back into the mitochondrial matrix. ATP
synthase, depicted to the right of the ETC in the simulation, uses the energy released by
protons’ movement back into the mitochondrial matrix to join a phosphate group with an ADP
molecule, generating ATP.
As ATP is created, protons are moving back into the matric through ATP synthase. What
happens to the potential energy of these protons?
Their potential energy is transferred to ATP. When protons move back into the matrix, their
potential energy is lowered.
Dissecting the ETC: 8
Which of the molecules are necessary for the electrons from NADH to move all the way to
oxygen?
Complex I, III, and IV, Q, and Cytochrome C. Complex II NOT needed.

ETC:9
As the electron move through the ETC, its Ep decreases. This is because each complex or
molecules has a greater affinity for electrons (a stronger “pull” than the previous one).
NOTE when affinity is high (electrons are held tightly) potential energy is low
Ultimately, electrons in the ETC are transferred to oxygen (making H2O), where they have the
lowest potential energy, because oxygen has the highest affinity for elections.

So, the electrons potential energy is highest when they are associated with complex I (where
they are bound the least tightly).
The electrons potential energy is lowest when they are associated with oxygen, as electrons
attach to oxygen, and have lower potential energy than they had with any of the other
components of the ETC. this is why oxygen is the final electron acceptor, and this helps the ETC
extract more energy from the electrons than it could if some other component was at the ETCs
end.

The potential energy that electrons lose as they “fall down” the ETC is used to pump protons
from the matrix into the intermembrane space. Because protons are repelled from the
intermembrane space, their occupation of that space stores potential energy (like lifting up a
ball).

FADH2: 10
Recall from section 1 that, like NADH, FADH2 (produced by the citric acid cycle) also transfers
electrons to the ETC. FADH2 GOES TO COMPLEX II.
So, the electrons from FADH2 to move all the way to oxygen, Complex II, III, IV are required as
well as Q and CytC, COMPLEX I not required.

Page 11
NADH results in a higher ATP production.

Page 12:
What would happen if NADH transferred electrons directly to Complex II instead of Complex I?
Fewer protons would be pumped, so less of the energy stored in NADH would be transferred to
ATP. (IF NADH entered the ETC after complex I, fewer protons would be pumped, and some of
the energy stored in NADH would be wasted (not used to make ATP).
Why can FADH2 not transfer electrons to complex I?
The electrons associated with Complex I have higher potential energy than they do later in the
ETC. FADH2 electrons do not have as much potential energy required to transfer them to
complex I. (Not as much Ep stored in FADH2 compared to NADH).
Apply what you have learned: 13
You have seen now that we humans, along with almost all other animals and plants and other
eukaryotes, obtain energy from food. You have unraveled the inner workings of the ETC, a core
component of cellular respiration, and hopefully you can appreciate why mitochondria are so
important to our cells. With this background, you can now investigate and make predictions
about the mechanisms for many diseases and drugs that affect cellular respiration.
Two of the most common causes of disability and death in developed countries are strokes and
heart attacks. Both of these are harmful, ultimately, because cells in important systems cannot
obtain enough oxygen. In the absence of oxygen, cells in your brain and heart will begin to die
in minutes.
In section 1, you saw that reducing oxygen made the simulated cyclist less efficient at extracting
energy from glucose.

Molecular mechanism of Asphyxiation: 14

Initially, when the ETC is deprived of oxygen and you attempt to transfer electrons from NADH
and FADH2, there is not much of an immediate effect, Protons are pumped, and the resulting
proton gradient is used by ATP synthase to make ATP.

Eventually, if oxygen is withheld for longer, the ETC can no longer oxidize (accept electrons
from any additional NADH or FADH2). The electron chain will fill up with electrons until it
cannot accept anymore…

So, what is the role of oxygen in the ETC?

Oxygen keeps the ETC running by removing electrons from complex IV. Oxygen has the
strongest affinity for electrons, so its able to pull electrons away from Complex IV, which keeps
the ETC from being “clogged up with electrons”.

Cyanide poisoning: 16
Cyanide is a popular drug in murder mysteries because eating as little as 200mg (0.2 grams) can
be fatal. Symptoms of cyanide poisoning can include confusion, seizures, difficulty breathing,
coma, and cardiac arrest.
Cyanide works by affecting cellular respiration. The simulation will let you give a bit of cyanide
to an innocent cyclist. In reality, a cyanide poisoned cyclist would not be pedaling for very long,
but the simulation shows the energetic effects only, ignoring the effects on the heart/brain
which could be fatal.
What is the effect of cyanide?
The cyclist moves much more slowly, despite using more glucose. This means that some ATP is
being made, but fairly little per each molecule of glucose. i.e. ATP production from glucose is
reduced.

How does cyanide decrease the amount of energy extracted from glucose:17
Cyanide poisoning is most similar to oxygen deprivation. In the ETC view, cyanide binds to
complex IV, and prevents the transfer of electrons to O2.
The only treatment would to be using agents that can bind to cyanide and keep it from blocking
complex IV activity.

Effective and dangerous Diet Drug: 18

Recall the weight loss drug dinitrophenol (DNP) that the cyclist tried taking at the beginning of
this section. The drug called her to lose weight, but it greatly reduced her speed.
Why might DNP cause weight loss?
People taking DNP obtain less energy from each glucose molecule so they must “burn” more
glucose than they otherwise would. The cyclist uses a lot of glucose even when stopped.

19:
What is the molecular mechanism of DNP?
DNP causes the inner mitochondrial membrane to leak protons into the matric. When DNP is
present, some protons are able to move back through the inner mitochondrial membrane into
the matrix without being used to make ATP.
Why is the cyclist using more glucose when taking DNP?
when DNP is present, fewer intermembrane protons are available to ATP synthesize to make
ATP, resulting in fewer ATP molecules produced per glucose molecule. Cells therefore use more
glucose to produce the same amount of ATP. ATP production is less efficient.
DNP is dangerous because if too many protons leaked through the inner membrane, the cyclist
would not be able to produce enough ATP to stay alive. In addition, because protons that leak
back into the mitochondrial matrix release energy as heat, hyperthermia (overheating) can
result.

20:
A drug that dramatically reduces ATP production or prevents the ETC from functioning at all
would be lethal
A promising diet drug reduces (but does not eliminate) the number of ATP molecules produced
per NADH molecule

Section Summary: 21
- The electron transport chain, by creating a proton gradient that stores potential energy,
contributes to the majority of ATP production in cells when oxygen is present.
- The electron transport chain oxidizes NADH and FADH2 into NAD+ and FAD, and it
reduces O2 to water
- The potential energy in NADH and FADH2 is used to pump protons into the
mitochondrial matrix into the intermembrane space
- ATP is produced by ATP synthase which harnesses the potential energy released by
protons moving back into the mitochondrial matrix from the intermembrane space
- fewer protons are pumped per FADH2 molecule than per NADH so less ATP is produced
per FADH2 then per NADH
- without oxygen, the electron transport chain stops functioning and the cell must rely on
glycolysis to generate ATP
Questions: 22
Why does the potential energy of protons increase when they move from the mitochondrial
matrix into the intermembrane space
Because the intermembrane space is positively charged, and like charges repel eachother, so by
packing a bunch of positively charged protons into the small volume of the intermembrane
space is quite like compressing a stiff string.

Suppose a molecule called XADH (similar to FADH2) could directly transfer 2 electrons to Cyt c
in the ETC. Which statement would be TRUE about XADH?
The cell would produce fewer ATP molecules of XADH than it does per molecule of FADH2
because compared to FADH2, XADH electrons skip complex II, Q, and Complex III, resulting in
fewer protons pumped and thus less ATP made.