Cellular respiration notes
o We eat to take in the fuels to make ATP which will then be used to help us build
biomolecules and grow and move and… live!
o heterotrophs = “fed by others” vs. autotrophs = “self-feeders”
o
o Tens of millions of ATPs in each cell…each cell uses about 10 million ATPs per
second…need to recycle…cant be making them from scratch all the time
o Happening in just about every cell of your body (pinch skin on arm), bone cells,
heart cells, lungs…everywhere!
o Local anesthetic please…
o Table sugar…disaccharide called sucrose…which is made from glucose and
fructose …two monosaccharides.
o Will use glucose as our example.
o Hitting on the MAJOR points…for every step I mention there are about 10-20
other intermediate steps…the classical equation of cellular respiration implies that
it is just that…a simple equation. In fact, the whole process of breaking down a
glucose mol. In a cell to extract the energy takes hundreds of steps.
SO, “Why do you suppose it takes so many steps?”. I mean, what is the biological
advantage of doing it in so many steps? Describe example of burning a sugar cube or
pouring gasoline all over the floor…idea here is that combustion = making heat energy
by burning fuels in one step ….respiration = making ATP (& less heat) by burning fuels
in many small steps
o By having many steps in which only a little energy is lost as heat during each
step, you avoid a dangerous heat buildup. You also have more control of the
process.
o GLYCOLYSIS
o Mobilization: essentially preparing and reshaping the glucose mol. for
other things.
o First, take an ATP mol., strip the phosphate off, and fasten the phosphate
to the glucose to make glucose-6-phosphate. Notice this has already cost
us energy to get things going.
o glucose-6-phosphate gets its internal shape adjusted in some steps I have
not shown here and add another phosphate from another ATP giving us
fructose-1,6-bisphosophate.
o So, at end of mobilization we are operating at a deficit of 2 ATPs
o Cleavage: split the fructose-1,6-bisphosophate into two 3-carbon mols.,
each called glyceraldehydes-3-phosphate.
o VERY IMPT: we started with one-6 carbon mol. Now we have two 3(C)
mols. We are going to follow the fate of only one of these to avoid
repetition but you have to realize the exact same thing is happening to the
other 3-carbon molecule…
o Oxidation: oxidation (from chem. Class) is the loss of an electron, adding
O, releasing energy, exergonic, removing H
o what is next is we strip a proton and two electrons off the
glyceraldehydes-3-phosphate and fasten them to an ion called NAD+…
o The NAD+ having picked up the 2 electrons and the proton is said to be
reduced (stores energy, endergonic, removal of O) and is now called
NADH
o the molecule left after the oxidation of glyceraldehydes-3-phosphate is
called 1,3-bisphosphoglycerate (3C).
o NAD+ is very impt. Without it we’d be stuck right here with all of this
glyceraldehyde-3-phosphate..and nowhere to go with it. We need a
good supply of NAD+ and shortly we will see where it comes from.
o Conversion to Pyruvate: (last step in glycolysis)
 Take 1,3-bisphosphoglycerate and carry it through a series of
separate reactions and rearrange its internal structure into
something called pyruvate or pyruvic acid.
 In doing so, we liberate enough energy to produce 2 ATPs
So, at beginning of glycolysis we spent 2 ATPs…we have just made 4 ATPs (2 from
each of the glyceraldehydes-3-phosphates)…
We now have two, 3-carbon pyruvate molecules and a net gain of 2 ATPs at the end of
glycolysis.
Approx. 95% of the energy that was in the original glucose molecule is stilled tied up
inside the two pyruvate molecules. …now we just need to begin ripping apart these
pyruvates to start getting loads of energy.
ASK:
most ancient form of energy capture… starting point for all cellular respiration
inefficient
generate only 2 ATP for every 1 glucose
in cytosol
why does that make evolutionary sense?
Evolutionary perspective
Life on Earth first evolved without free oxygen (O2) in atmosphere…
energy had to be captured from organic molecules in absence of O2
Organisms that evolved glycolysis are ancestors of all modern life
all organisms still utilize glycolysis
The enzymes of glycolysis are very similar among all organisms. The
genes that code for them are highly conserved.
They are a good measure for evolutionary studies. Compare
eukaryotes, bacteria & archaea using glycolysis enzymes.
Bacteria = 3.5 billion years ago
glycolysis in cytosol = doesn’t require a membrane-bound
organelle
O2 = 2.7 billion years ago
photosynthetic bacteria / proto-blue-green algae
Eukaryotes = 1.5 billion years ago
membrane-bound organelles!
Processes that all life/organisms share:
Protein synthesis
Glycolysis
DNA replication
REMEMBER that in glycolysis we needed a supply of NAD+ and that ended up
producing a supply of NADH?
ASK: Can someone figure out a way to get us all the NAD+ we wanted?
ANSWER: Re-oxidize the NADH. That would give you NAD+…but we would still
have some H left over. AND what you do with that left over H represents one of the
great biochemical divisions between groups of organisms.
(1) if you take that H and donate it to an organic mol. in the absence of oxygen, the
process is called fermentation. This is called anaerobic respiration and is
characteristic of single-celled organisms like bacteria and yeasts. (biological and
human importance: alcoholic fermentation…yeast takes care of the surplus H
from the oxidation of NADH by grabing a pyruvate molecule and then splitting it
into a mol. of carbon dioxide which it dumps into the atmosphere and a 2-carbon
mol. called acetaldehyde…the acetaldehyde picks of the extra H and what is left
is good ol’ ethanol…ethyl alcohol; , baking of bread)
(2) If the H is dontate to an oxygen to make water, we then have oxidative, or aerobic
respiration which we will talk about tomorrow.
Lactic acid:
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Type of fermentation
Normally muscles operate by oxidative respiration which we’ll discuss next time.
There are time when the demand for energy release is greater than the capacity of
the circ. System to bring oxygen to the muscle cells.
There is a shortage of oxygen
Normally if a higher organism’s cell runs out of oxygen it shuts down its
operation
But there is a kind of “emergencies only” metabolic pathway that lets you get a
little energy out of glucose, even without oxygen.
Combine pyruvate and NADH and covert it into lactic acid and NAD+
Unfortunately lactic acid tends to be toxic as it starts to build up in the absence of
sufficient oxygen, eventually the muscle will stop functioning.
This is the point where you just cant do that last bench press no matter how hard
you try
When you stop the physical activity youre still breathing hard and the incoming
oxygen permits the breakdown of the lactic acid into nontoxic products, so there
are no permanent effects.
The Citric Acid Cycle and Electron Transport

Today you will learn about something entirely beautiful. Ideas can be beautiful,
as well as things. You can have a gorgeous painting or an ugly painting. You can
have a beautiful idea or an ugly idea. A beautiful ideas has symmetry and is an
elegant way of going about something. You will be stunned when you see how
pretty this idea is, and you will be amazed at the cleverness of the people who
figured it out.

Aerobic respiration. Remember, starting with pyruvate. This time we will end
up with a quite a few ATPs and a couple of simple compounds that are not broken
down further by the cell. These compounds are carbon dioxide and water.
These represent by-products---not waste products. A waste is something you
don’t use at all in a process, like the rock part of gold ore; a by-product is
something that is left over after you finish your process, like the exhaust that
comes out of your car’s tailpipe. The carbon dioxide is just dumped—it diffuses
out of the cell and into the circ. System and eventually gets to the atmosphere.
Humans simply breathe it out. The by-product water can be used if the cell needs
it, or if the cell has enough water, it can be dumped – breathed out, sweated out,
or peed out.

Oxidize the pyruvate….which means the pyruvate is donating electrons to
something else. An oxidizing agent picks up the electrons.
After oxidizing the pyruvate, something drastic happens…the pyruvate mol.
yields a couple of electrons and a tagalong hydrogen, all of which we use to
reduce NAD+ into NADH.
At the same time, we strip off a carbon dioxide, which leaves us with a molecule
with how many carbons? (yes, TWO)
This 2C mol is a functional group called an acetyl group.
This acetyl group immediately gets combined with a carrier mol. ….its function
is to carry an impt mol. or group from one mol. to another. This particular
carrier mol. is called coenzyme A
The combined acetyl group and the coenzyme A are called acetyl coenzyme A or
acetyl CoA
Remind students that we will at a later point recover some of those electrons from
the NADH in this step to make ATPs….but for now lets see what happens to the
acetylCoA
AcetylCoA is a VERY important compound. It can be produced by the
decarboxylation (the removal of CO2) of pyruvate. You can also get acetylCoA
by breaking down proteins and fats. It is in some ways a “crossroads” compound
b/c it is the point at which the REAL extraction of energy begins…regardless of
the source of the energy –containing compound.
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going to get rid of the acetyl group but leave lots of protons (H+) and electrons
that we can use to make ATPs.
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First thing is to combine the acetyl group with a 4C organic acid called
oxaloacetic acid.
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This produces a 6-carbon compd. called citric acid…yup, orange juice citric acid.
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Remind them that you are leaving out many steps but hitting on the major
transitions
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Take the 6C citric acid and pull off a CO2 which disappears; we wont see it again
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We pull off a couple of electrons and hydrogen and reduce an NAD+ to NADH.
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What we are left with is a 5C compound called alpha-ketoglutaric acid.
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Taking our alpha-ketoglutaric acid we pull off another CO2 , reduce an NAD+ to
NADH and because we are breaking a lot of bonds in this step, we can make an
ATP from ADP and phosphate group. This is called substrate-levelphosphorylation.
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A lot going on…what we are left with is a 4-carbon compd called succinic acid.
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Next step is kind of interesting. By rearranging this mol. of succinic acid in a way
that changes its single bonds into double bonds, we can pull out a hydrogen and a
couple of electrons. Up until now, what have we done with this H and these
electrons? (we have reduced NAD+ to an NADH)
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But now, because of the way we got these electrons and the H (single to double
bond move) we have to use another electron carrier mol. called FAD. FAD can
pick up two Hydrogens when it is reduced, so what we end up with when we
rearrange our 4carbon succinic acid is another 4 carbon acid called fumaric acid
or FADH2
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Patience…we are almost done. We now add a water to our 4-carbon fumaric
acid, not to dissolve it, but to donate the hydroxyl group in the water to the
fumaric acid. When we have done this we have another 4-carbon acid, malic
acid.
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Now, watch carefully. The hand is quicker than the eye. We break a little bond,
pull off a H and a couple of electrons which I give to my beautiful assistant
holding a NAD+, which she reduces to NADH and PRESTO…I have oxaloacetic
acid…which is what we started with and the acetyl group has completely
disappeared! TA DA!
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MAIN POINT: What we really want to do in this whole process is pull as many
protons and electrons out of the original glucose mol. as we can because we can
use these in a way I will describe shortly to make ATPs
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MAIN POINT: the acetyl group we started with has plenty of these protons and
electrons but to pry them out we have to , as it were, prepare the acetyl mol. We
do this by making it into citric acid when we combine it with oxaloacetic acid.
This is where the beautiful part comes in…clearly we will need a big supply of
oxaloacetic acid if we have a lot of acetyl molecules. It would take a lot of energy
to synthesize these oxaloacetic acids but by having this cyclic process, the end
product can be recycled over and over at very little cost. Essentially it is a chain
of equations that chase their tails.
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So, what happened to the acetyl group? Remember along the way we liberated 2
carbon dioxides? The formula of the cetyl group is C2H3O. You can see that if
you are going to give off 2 CO2 molecules in the cycle, and you are going to start
and end with oxaloacetic acid you are missing something….oxygen.
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Where does the oxygen come from? From oxygen in the air? No.
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It comes from the water. By adding water at the appropriate place, pull it apart to
get the oxygen, and use the leftover hydrogen from the water to fill vacant bond
locations where I pulled off my carbons.
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THUS, you really need oxaloacetic acid, acetyl CoA, and water to make the Krebs
cycle work. (named after Sir Hans Krebs…the genius who first worked out the
details)
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Summary: after the citric acid wheel has made one turn, and processed 1 acetyl
molecule, we have 1 ATP, 3 NADH and 1 FADH2 each containing hydrogen and
electrons picked up during the Krebs cycle.
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Remember however, that a mol. of glucose yields 2 acetyl molecules so after the
2 acetyls pass through the citric acid cycle, there are a total of 2ATPs, 6 NADH
and 2 FADH2
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Now we want to see how the energy contained in those electrons can be used to
make ATPs
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<<remind them of mito. structure>>
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take our NADH and FADH2 mols. to the inside of the inner membrane and here
is the first critical event.
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We are going to take the hydrogens and electrons off the NADH and FADH2 and
separate them.
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Different things will happen to them. Keep it straight that one thing is happening
to the electrons and something different is happening to the hydrogens.
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Wait a minute! If you are taking electrons and hydrogens off the NADH what
do you think happens to the NAD part? Guess. (answer: it gets changed back to
NAD+ where it can go back to the citric acid cycle and pick up more hydrogens
and electrons!)
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Look at hydrogens first: there they are…sitting at the entrance to the channels.
Remember diffusion right? Hydrogens would diffuse through the holes of the
membrane and after awhile would reach equilibrium…the concentration of H
outside would be the same as the conc inside.
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Initially you started with more hydrogens on the inside…lets say you wanted to
finish with more hydrogens on the outside…could you do it? How?
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You could spend some energy. You could pump those hydrogens through the
membrane …as many as you had energy for. What would your source of energy
be? (answer: the electrons! You could use the energy in the electrons you pulled
off the NADH. They are sitting in the right spot…right there on the inside with
the hydrogens…)
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Remember from chem. class that electrons can exist at different energy
levels…if you remove a little energy from the electron it slips down to a lower
energy level.
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The electrons arriving from the citric acid cycle are at a very high energy level.
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We pass these electrons through a series of electron-transport molecules. Each
time we pass the electron on to the next transport mol, the electron loses a little
energy. Sort of like a leaky bucket. Guess what we use that energy for? Of
course, we pump protons out!
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Go through image on ppt starting with the truck and working through the
lineup…electrons are being passed along this electron-transport chain which
provides energy to operate the proton pump.
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Cytochrome a3 takes 4 electrons, picks up 4 hydrogens on the outside of the inner
membrane and uses the electrons and the hydrogens to reduce a molecule of
oxygen to 2 molecules of water.
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Nobody knows exactly how the proton pump works. The reactions work so fast
that we cant tell what is happening…potential Nobel prize for you!
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So, now we have all those protons on the outside of the inner membrane and we
use some of them along with the electrons and free oxygen, to form water, which
is our final stable compound, the end product of respiration.
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Why do we want all those protons out there??
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We have used a lot of energy to get those protons out there…what will happen to
all those protons? (answer: they are going to want to get back inside)
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“want” is not really the right term however a diffusion gradient is created…
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as protons are forced back into the membrane the energy contained in the protons
is used to bind phosphate to ADP to make ATP.
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In addition to the diffusion gradient there is another source of energy. More
positive protons outside membrane relative to inside so there is a difference in
electrical potential between the two sides…that difference in electrical potential is
used to do work as well….to make ATP
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most of the energy released from the glucose is converted to ATP in this ETC in a
process called chemiosmosis.