How long can you hold your breath? Most
people can only manage between 30 and 45
seconds before they need to start
breathing again. Just 3 to 4 minutes
without oxygen is often enough to cause
brain damage or death.
Fun fact: before I started BOGObiology, I
worked as a medic for a number of years.
We often referred to the rule of three:
humans can survive about three weeks
without food, three days without water,
and just three minutes without oxygen.
The oxygen clock starts ticking the
second the person stops breathing.
This is why we'd drive really, really fast to
get to all of our calls. But why do we
need oxygen so badly?
How do our cells use it, and what happens
to them if they don't get it? This video
will review the process of cellular
respiration in order to answer these
questions and more. This is definitely
going to get pretty complicated
particularly when we get to the
reactions portion with the Krebs cycle
and electron transport chain. If you'd
like to download a set of guided notes
I've left a link to them in the video description.
Ok here we go! In respiration
our goal is to use glucose and oxygen in
order to generate ATP plus some water
carbon dioxide and heat on the side.
Notice the similarities between this
cellular respiration equation and the
equation for photosynthesis. The two
processes are essentially complementary.
ATP is a universal cellular energy
currency which the body spends to do
virtually every action that keeps us
alive. There are two kinds of cellular
respiration aerobic and anaerobic.
Aerobic respiration requires lots of
oxygen but it also gives you the most
bang for your glucose buck. Anaerobic
respiration occurs when there is very
little or no oxygen. It yields a little
bit of energy but not nearly as much as
aerobic respiration. This video will
mostly cover aerobic respiration. If
you'd like me to make a detailed video
about anaerobic respiration /
fermentation be sure to let me know in
the comments. In eukaryotes respiration
takes place in the cytoplasm and in the
mitochondria the mitochondria have inner
and outer compartments and a portion of
cellular respiration takes place in each
one. The outer compartment is called the
inter membrane space and the inner
compartment is called the matrix.
Aerobic respiration consists of three major
steps; glycolysis the Krebs cycle and the
electron transport chain. In glycolysis uses
up glucose and also invests a tiny bit
of ATP in order to generate some more
ATP. The krebs cycle generates still more
ATP and some carbon dioxide as a waste
product.
We also throw in a little bit of water
to the krebs cycle but not much.
The electron transport chain uses up oxygen
and generates water plus a lot of ATP.
So, now that we've seen the overall picture
we're going to dive into the process
itself beginning with glycolysis. The
first step in both aerobic and anaerobic
respiration is glycolysis which occurs
in the cytoplasm of the cell. This step
does not require any oxygen which is why
it's common to both types of respiration.
We'll start with a molecule of glucose
which has 6 carbons but we need to break
it into pieces in order to use it. To
jumpstart this breakdown, we're going to
invest 2 ATP into glycolysis glycolysis
will eventually yield 4 ATP for a net
yield of 2. It first forms a very
unstable compound called
Fructose 1 6 bisphosphate
and the formation costs 2
ATP. Then this molecule splits into two
kinds of 3 carbon molecules; DHAP
(dihydroxyacetone phosphate) and PGAL
(glyceraldehyde 3-phosphate). Eventually
all the D HAP converts into PGAL; a more
useful molecule for our purposes.
Note that glyceraldehyde-3-phosphate is
a really long name so luckily it has
several nicknames. Different parts of the
world use GALP,  G2P, GADP etc all to refer
to the same molecule. After still more
chemical reactions the PGAL is going to
be converted into pyruvate. The process
of converting PGAL into pyruvate
eventually generates 4 ATP and it also
involves two molecules of something
called NADH. The pyruvate making process
generates waste products of electrons
and protons. NADH is known as a mobile
electron carrier. It will transport these
particles to another set of reactions
later on and then come back for more,
much like a dump truck. When the NAD+
is loaded up with the electrons and
proton, we say it's been "reduced" into
NADH. When the NADH is unloaded we say
it's oxidized back into NAD+.
Remember O.I.L.R.I.G. oxidation is losing and reduction is gaining.
Cellular respiration also uses another mobile electron carrier called fadh2. In summary
we started with one glucose molecule and
broke it into
pyruvate and also recharged two NADH.
It's often really useful to keep score
as we go through the reactions. As we
progress, we'll be updating a chart that
looks like this. So far we've made four ATP
and spent 2. Then we recharged 2
molecules of NADH and zero fadh2. Next up
we have the prep steps. These are
technically part of glycolysis but my
students found it far easier to
understand how glycolysis and the Krebs
cycle are connected when we outlined
this particular set of reactions
independently. The prep steps occur in
the cytoplasm just like glycolysis. We
need to slice and dice the products of
glycolysis a little bit in order to use
them in the Krebs cycle. During the prep
steps we're going to modify our 3 carbon
molecule of pyruvate using something
called coenzyme A. Coenzymes store
energy in their bonds and help enzymes
work more effectively. At the end of the
prep steps we generate 2 molecules of
something called acetyl coenzyme A or
Acetyl CoA. We also generate 2 molecules
of CO2 and two reloaded molecules of
NADH. Notice how pyruvate had 3 carbons
and how those 3 carbons get reshuffled
into a molecule with two carbons and a
molecule with one carbon. We haven't
magically lost any carbons anywhere in
here they've just been rearranged.
Remember also the aerobic respiration
produces carbon dioxide as a waste
product and this is one of the places
that it comes from. Before moving on to
the Krebs cycle let's update our
scorecard. Here we made zero ATP, 2 NADH
and zero FADH2. Now for the Krebs cycle.
The Krebs cycle, also known as the citric
acid cycle, takes place in the inner
compartment of the mitochondria known as
the matrix. The Krebs cycle is going to
use the products of glycolysis and the
prep steps and work to recharge a few
ATP molecules and reload a bunch of nadh
and another carrier molecule called
fadh2. We will cash in these carrier
molecules for ATP later on. Each of the
following steps are performed by enzymes
but the exact mechanisms of how they
work are beyond the scope of this video.
We're going to kick off the Krebs cycle
with something we just made in the prep
steps; acetyl co a, which has two carbons.
The acetyl co a from the prep steps adds
on to a new four carbon molecule called
oxaloacetate to form an intermediate
molecule. By looking at the diagram so
far you can probably guess how many
carbons this intermediate molecule has.
Two carbons plus four carbons equals six
carbons. From here we add a series of
enzymes to convert each molecule into
the next one. The next molecule is
isocitrate which is similar to citrate
and also has six carbons. Next we form
alpha ketoglutarate which only has five
carbons. So what happened to that sixth
carbon? It's released in the form of
carbon dioxide. Next up is a molecule
called Succinyl CoA which has four
carbons. Based on the last step you can
probably guess what happened to that
fifth carbon; it was released in the form
of a second molecule of carbon dioxide.
Next up is a molecule called succinate
which also has four carbons, then comes
fumarate which has four carbons, and then
malate which also has four carbons. We
also add a molecule of water here to get
this final molecule. Last we convert the
malate back into oxaloacetate where we
started and the cycle can begin again.
I'm not usually a big fan of
memorization but if you're forced to
memorize the krebs cycle here's a little
trick that I learned in undergrad.
"Cindy is kinky so she $%&#s more often". However
if you need something a little more
g-rated you might go with 'Cindy is keto
so she feeds more obnoxiously". So now
we've mapped out how the Krebs cycle
cycles carbon and where the carbon
dioxide waste product comes from. Let's
go back in and add in ATP and also add
in all of our electron carriers.
We reload three molecules of NADH during
the Krebs cycle the first when we
convert isocitrate into
alpha-ketoglutarate and the second when
we convert alpha-ketoglutarate into
Succinyl CoA. The third is when we
convert malate into oxaloacetate. We
recharge a single molecule of ATP
between Succinyl CoA and Succinate and then
we also reload a new molecule called
FAD into fadh2 between succinate and fumerate. However all of the above is per
molecule of pyruvate and since each
glucose is broken into TWO molecules of
pyruvate, this cycle can turn twice per
molecule of glucose. So let's do a little
Krebs Cycle math. One rotation of this
cycle makes one ATP 3 NADH 1 FADH2 and
1 co2 but since the cycle turns twice
we actually make double that for each
molecule of glucose we put in. In total
we now have 4 ATP 10 NADH
and 2 FADH2. Now let's move on to the
electron transport chain. The electron
transport chain is the real moneymaker
of cellular respiration; in a really
efficient cell it can make about 34 ATP
per molecule of glucose. This last set of
steps is essentially two major parts; the
electron transport chain and something
called chemiosmosis. The ETC creates a
powerful proton gradient with lots of
potential energy. The chemiosmosis
exploits this gradient to generate
recharged ATP. We call these two
processes together oxidative
phosphorylation. To start with let's
review how the e.t.c establishes that
gradient. To make the gradient we need a
membrane with more protons on one side
and fewer protons on the other side. The
membrane can have channels in it but
they need to be one-way channels to keep
the protons from sneaking back to the
other side and re-establishing
equilibrium. In respiration this gradient
occurs across the membrane that
separates the compartments of the
mitochondria. It's in between the
mitochondrial matrix, the inner
compartment, and the inter membrane space,
the outer compartment. This membrane is
studded with protein complexes several
of which include proton pumps. These
one-way pumps maintain the gradient. NADH
and FADH2 are going to deliver electrons
and protons to the area on the matrix
side of the membrane. Every time an
electron contacts one of these pumps
it's going to pump another proton from
the matrix into the intermembrane space
and make the gradient stronger. Where do
the protons for the gradient come from?
Conveniently they're also delivered by
the NADH and the FADH2. But why is the
process called a "chain"? This is because a
high-energy electron is transported
through a chain of proteins. At each step
the electron's energy is reduced and that
energy is used to do something useful.
It works much like a conveyor belt
delivering electrons from one protein to
the next. Electrons can enter at two
different points but they always travel
in the same direction. Let's work through
the process first a molecule of NADH is
broken down into hydrogen, electrons and
NAD. This pair of electrons from the NADH
are going to flow through the electron
transport chain starting at complex I.
Look at the diagram and see how many
proton pumps you think
they will pass through. The pair of
electrons delivered by the NADH will
flow through three different proton
pumps pumps; I, III and IV. Each time
they touch one, the pump will suck a new
proton into the intermembrane space
strengthening the proton gradient. Along
the way they will be transferred through
to other protein complexes; ubiquinone
and cytochrome c, but these complexes
don't do any pumping. But what about
FADH2? FADH2 also delivers electrons. It
delivers them to complex II. Complex II
then transfers the electrons to
ubiquinone then to complex III,
cytochrome C, and then complex IV. The
pathway is almost the same it just uses
a different on-ramp. To make sure we're
on the same page, look carefully at the
diagram and figure out how many protons
get pumped as a result of one molecule
of FADH2. Since FADH2's electrons only
make it through proton pumps III and
IV, we can conclude that each molecule
of FADH2 will result in pumping two
protons into the intermembrane space.
Regardless of whether the electrons
originated from NADH or from FADH2 they
need to go somewhere once they reach the
end of the electron transport chain.
This is where we finally get to understand
why oxygen is so important. Oxygen is
known as the final electron acceptor in
the electron transport chain. The spent
electrons bind with protons and oxygen
to form molecules of water. Without
oxygen to pick up the electrons at the
end of the chain, the proteins would
become "clogged" with electrons. The pumps
would stop working, the gradient would
disappear, and then we couldn't recharge
any more ATP. Essentially, Cyanide and
suffocation in general cause death via
electron constipation. Unless oxygen
arrives promptly to deal with the "clog"
the prognosis is ...crappy!
Now that we've discussed how the electron transport
chain makes a gradient, we should discuss
how the gradient is used. Currently there
are a ton of protons in the
intermembrane space of the mitochondria
and very few in the matrix. This gradient
has a lot of potential energy and the
protons are desperate to re-establish
equilibrium. The only route that flows
from the intermembrane space back into
the matrix is via the ATP synthase
protein. Notice how there is just one ATP
synthase passage
for every three proton pumps. This means
that the competition to leave through
the one available exit is pretty fierce.
This flow of ions from high to low
concentration across a semipermeable
membrane is known as chemiosmosis. Every
time a proton passes through the ATP
synthase protein, it recharges a
molecule of ADP back into ATP. It tacks a
phosphate group onto ADP making it into
ATP. We call this process "phosphorylation".
Remember how we figured out how many
protons a molecule of NADH and FADH2
would yield under ideal conditions? This
is where we cash in those molecules for
ATP. For each molecule of NADH, we pumped
three protons and can recharge three
molecules of ATP. For each molecule of
FADH2, we pumped two protons and thus can
recharge two molecules of ATP. In total
we made four ATP, plus another 30 from
NADH, and another 4 from FADH2. So in
summary we used both glucose and oxygen
to generate carbon dioxide, ATP and a
little bit of water. So that's pretty
much it on cellular respiration and I
hope you found this video useful! If you
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