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JOHN ESSIGMANN: We're now on
storyboard 12, session 13.

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Let's take a look
first at panel A.

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I mentioned earlier
that respiration

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is the oxidative metabolism
of all metabolic fuels,

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carbohydrates as well as lipids.

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If we were starting
with a carbohydrate then

00:00:36.410 --> 00:00:40.250
respiration starts with the
pyruvate dehydrogenase reaction

00:00:40.250 --> 00:00:42.770
and then proceeds
into the TCA cycle,

00:00:42.770 --> 00:00:47.330
and then into electron transport
and oxidative phosphorylation.

00:00:47.330 --> 00:00:50.570
If the acetylcholine comes from
fatty acid oxidation, which

00:00:50.570 --> 00:00:52.460
we'll cover later,
then we do not

00:00:52.460 --> 00:00:55.520
have to do the pyruvate
dehydrogenase step.

00:00:55.520 --> 00:00:58.820
Three molecules of NADH
and one molecule of FADH2

00:00:58.820 --> 00:01:01.370
are produced as the
carriers of electrons

00:01:01.370 --> 00:01:03.740
from the intermediates
in the TCA cycle

00:01:03.740 --> 00:01:08.120
from each input molecule
of acetyl coenzyme A.

00:01:08.120 --> 00:01:09.740
As I mentioned a
number of times,

00:01:09.740 --> 00:01:13.970
we look at NADH and FADH2 as
relatively mobile electron

00:01:13.970 --> 00:01:15.124
carriers.

00:01:15.124 --> 00:01:16.790
They're going to be
picking up electrons

00:01:16.790 --> 00:01:19.460
from intermediates and
biochemical pathways

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and then they bring
those electrons

00:01:21.500 --> 00:01:23.810
into the mitochondrial
inner membrane, where

00:01:23.810 --> 00:01:26.900
the reducing equivalents are
passed along to the electron

00:01:26.900 --> 00:01:28.310
transport chain.

00:01:28.310 --> 00:01:30.260
Ultimately the
electrons will end up

00:01:30.260 --> 00:01:34.120
being deposited into
oxygen to make water.

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Let's turn to panel B
where I'm going to start

00:01:36.520 --> 00:01:38.440
laying out the big picture.

00:01:38.440 --> 00:01:40.930
In this small cartoon
we see fuel being

00:01:40.930 --> 00:01:43.420
oxidized to carbon dioxide.

00:01:43.420 --> 00:01:46.090
The electrons are passed
to either in NAD-plus,

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or FAD to form the
reduced cofactor.

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The reduced co-factors
find their way

00:01:51.910 --> 00:01:54.220
to the mitochondrial
inner membrane

00:01:54.220 --> 00:01:56.110
and the electrons, or
reducing equivalents,

00:01:56.110 --> 00:01:59.050
are passed to oxygen
to make water.

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This process is
highly exergonic.

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And we'll do a model
calculation in a minute

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to show just how
energy yielding it is,

00:02:06.310 --> 00:02:09.830
resulting in the liberation
of a lot of free energy.

00:02:09.830 --> 00:02:13.480
That energy is captured
by the movement of protons

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from one side of the
mitochondrial inner membrane

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to the other side
of the membrane.

00:02:18.310 --> 00:02:21.970
In this process you're taking
a low concentration of protons

00:02:21.970 --> 00:02:25.540
and creating a relatively
high concentration of protons.

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That's an uphill process that's
going to require an energy

00:02:28.990 --> 00:02:31.870
input, and the energy
from nutrient oxidation

00:02:31.870 --> 00:02:35.650
is what powers this
generation of an ion gradient.

00:02:35.650 --> 00:02:38.890
Concentrating the protons
in a small defined space

00:02:38.890 --> 00:02:41.230
is kind of like
charging a battery.

00:02:41.230 --> 00:02:44.830
It took energy to create that
high concentration of protons.

00:02:44.830 --> 00:02:48.820
We'll see that nature invented a
way to channel the protons back

00:02:48.820 --> 00:02:53.110
through a device and a way to
capture the energy released

00:02:53.110 --> 00:02:55.390
when the gradient is dissipated.

00:02:55.390 --> 00:02:57.820
That energy can be
captured in various ways,

00:02:57.820 --> 00:03:01.860
enabling us to be able to
do useful things with it.

00:03:01.860 --> 00:03:03.740
For example, the
energy could be used

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to accomplish the otherwise
energy requiring process

00:03:06.830 --> 00:03:10.160
of putting a phosphate
onto ADP to make ATP,

00:03:10.160 --> 00:03:13.970
and that way the energy is
captured in a chemical bond.

00:03:13.970 --> 00:03:16.280
Alternatively, let's think
of a situation in which

00:03:16.280 --> 00:03:18.380
you may need to generate heat.

00:03:18.380 --> 00:03:20.060
You could allow
the protons simply

00:03:20.060 --> 00:03:23.090
to flow back across the
membrane through a channel.

00:03:23.090 --> 00:03:24.830
The energy of the
proton gradient

00:03:24.830 --> 00:03:27.170
would then be released as heat.

00:03:27.170 --> 00:03:30.260
Thirdly, we can perhaps allow
the protons to flow back

00:03:30.260 --> 00:03:33.530
through a device that
creates rotary movement

00:03:33.530 --> 00:03:35.780
and that's how, for
example, a flagellar

00:03:35.780 --> 00:03:38.690
motor can spin to move
a bacterium from one

00:03:38.690 --> 00:03:40.400
place to another.

00:03:40.400 --> 00:03:43.490
Let's now turn to
panel C. We've seen

00:03:43.490 --> 00:03:45.590
earlier that
oxidation can result

00:03:45.590 --> 00:03:48.710
in the production
of NADH or FADH2.

00:03:48.710 --> 00:03:51.590
To begin let's consider NADH.

00:03:51.590 --> 00:03:54.650
In this panel you can
see the NADH oxidized

00:03:54.650 --> 00:03:56.210
where the electrons
flow-- and it

00:03:56.210 --> 00:03:57.890
doesn't matter what
the path of the flow

00:03:57.890 --> 00:04:01.250
is-- all the way to
oxygen. Thermodynamics

00:04:01.250 --> 00:04:04.210
gives us the tools to
calculate how much energy you

00:04:04.210 --> 00:04:06.910
would get in this process.

00:04:06.910 --> 00:04:09.520
JoAnne taught you a lot
about thermodynamics

00:04:09.520 --> 00:04:11.710
in biological systems,
And this is just

00:04:11.710 --> 00:04:13.540
a repeat of what she said.

00:04:13.540 --> 00:04:15.520
But what I'm going
to do is put what

00:04:15.520 --> 00:04:19.149
she said into a concrete,
practical example.

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I've drawn out at
the bottom of panel C

00:04:21.430 --> 00:04:24.640
the overall reaction, showing
electrons going from NADH

00:04:24.640 --> 00:04:27.940
to oxygen in the
forward direction.

00:04:27.940 --> 00:04:31.360
Now, of course, we could also
think about the back reaction,

00:04:31.360 --> 00:04:34.630
where electrons would flow
from water into NAD-plus

00:04:34.630 --> 00:04:36.400
to form NADH.

00:04:36.400 --> 00:04:39.110
At this point this is just an
equation on a piece of paper

00:04:39.110 --> 00:04:40.840
and we don't know
in which direction

00:04:40.840 --> 00:04:43.240
the reaction is
overall favorable.

00:04:43.240 --> 00:04:45.850
That is, is it favorable
in the forward direction

00:04:45.850 --> 00:04:49.120
as drawn, left to right, or
in the reverse direction,

00:04:49.120 --> 00:04:50.560
right to left?

00:04:50.560 --> 00:04:52.990
The reaction from left
to right is the direction

00:04:52.990 --> 00:04:57.130
we usually think about in the
context of nutrient oxidation.

00:04:57.130 --> 00:05:00.070
Interestingly, the
reaction from right to left

00:05:00.070 --> 00:05:01.670
is photosynthesis.

00:05:01.670 --> 00:05:04.060
So both directions
are biologically used,

00:05:04.060 --> 00:05:06.010
but we'll see that
one of the directions

00:05:06.010 --> 00:05:09.010
will require substantial
energy input in order

00:05:09.010 --> 00:05:11.880
to make it biologically useful.

00:05:11.880 --> 00:05:14.370
Probably you can appreciate
that photosynthesis

00:05:14.370 --> 00:05:17.130
is the energy requiring
process, because we all

00:05:17.130 --> 00:05:18.840
know that sunlight
is needed to make

00:05:18.840 --> 00:05:22.440
the process thermodynamically
and kinetically favorable.

00:05:22.440 --> 00:05:24.960
We don't cover photosynthesis
in 5.07, so let

00:05:24.960 --> 00:05:27.080
me say a few words about it.

00:05:27.080 --> 00:05:30.660
In photosynthesis nature
takes electrons from water

00:05:30.660 --> 00:05:34.110
and uses them to reduce
NADP-plus to NADPH.

00:05:34.110 --> 00:05:37.560
Note that I said NADP-plus,
and not NAD-plus,

00:05:37.560 --> 00:05:40.770
but for the purposes
here they are equivalent.

00:05:40.770 --> 00:05:43.380
In the case of photosynthesis
we know intuitively

00:05:43.380 --> 00:05:45.810
that the overall process
is powered by light,

00:05:45.810 --> 00:05:48.630
so in going from right to
left the process intuitively,

00:05:48.630 --> 00:05:51.390
once again, should
require energy.

00:05:51.390 --> 00:05:53.760
By contrast, nutrient
oxidation, where

00:05:53.760 --> 00:05:56.430
we go from left to
right in this equation,

00:05:56.430 --> 00:05:59.280
should be a process
that generates energy.

00:05:59.280 --> 00:06:03.220
But intuition aside,
let's do the calculation.

00:06:03.220 --> 00:06:06.060
So the question is,
in which direction

00:06:06.060 --> 00:06:09.270
is the equation at the bottom
of panel C thermodynamically

00:06:09.270 --> 00:06:14.600
favorable-- left to
right or right to left?

00:06:14.600 --> 00:06:17.380
Let's take a look
now at panel D.

00:06:17.380 --> 00:06:19.450
You'll see here that I
have split the master

00:06:19.450 --> 00:06:22.060
equation into half reactions.

00:06:22.060 --> 00:06:24.340
I always write out
the half reaction

00:06:24.340 --> 00:06:26.330
in the direction of reduction.

00:06:26.330 --> 00:06:28.870
For example, look at the
second half reaction.

00:06:28.870 --> 00:06:31.540
It shows that half
a mole of oxygen

00:06:31.540 --> 00:06:34.880
plus two protons, plus two
electrons, go to water.

00:06:34.880 --> 00:06:36.790
Again, I've written
out these reactions

00:06:36.790 --> 00:06:38.250
in the direction of reduction.

00:06:38.250 --> 00:06:40.330
It's just the way I do it.

00:06:40.330 --> 00:06:42.370
Next I go to the
redox chart, that

00:06:42.370 --> 00:06:45.940
is the table of redox potentials
of electrochemical reactions,

00:06:45.940 --> 00:06:49.330
and I figure out what the
standard energies are for each

00:06:49.330 --> 00:06:51.070
of these half reactions.

00:06:51.070 --> 00:06:56.470
As you can see, it's 0.32
volts, and, plus 0.82 volts

00:06:56.470 --> 00:06:59.660
respectively, for the
two half reactions.

00:06:59.660 --> 00:07:02.260
Next I use a variant
of the Nernst equation

00:07:02.260 --> 00:07:04.630
to calculate the free
energy and ultimately

00:07:04.630 --> 00:07:06.740
the directionality
of the reaction.

00:07:06.740 --> 00:07:10.840
The equation I use is
delta G naught prime equals

00:07:10.840 --> 00:07:13.810
N times Faraday's constant,
times the difference

00:07:13.810 --> 00:07:16.980
in the reduction potentials
of the two half reactions.

00:07:16.980 --> 00:07:20.380
To find delta E
naught prime, we look

00:07:20.380 --> 00:07:22.360
at the reaction that
I've written out,

00:07:22.360 --> 00:07:24.340
the overall reaction,
and we looked

00:07:24.340 --> 00:07:27.550
at see which is the
electron acceptor,

00:07:27.550 --> 00:07:30.040
in which is the
electron donor the way

00:07:30.040 --> 00:07:32.110
the reaction was written.

00:07:32.110 --> 00:07:34.480
Then we subtract the
reduction potential

00:07:34.480 --> 00:07:40.130
of the electron receptor from
that of the electron donor.

00:07:40.130 --> 00:07:43.070
The way the equation is
written, left to right, oxygen

00:07:43.070 --> 00:07:44.930
is the electron acceptor.

00:07:44.930 --> 00:07:49.460
It's reduction potential is plus
0.82 volts, so delta E naught

00:07:49.460 --> 00:07:55.580
prime is plus 0.8 to
minus a minus 0.32,

00:07:55.580 --> 00:08:00.870
or a total of plus 1.14 volts.

00:08:00.870 --> 00:08:02.630
In the Nernst
equation, the number

00:08:02.630 --> 00:08:04.970
of electrons transferred
in this case is two,

00:08:04.970 --> 00:08:08.600
and Faraday's constant
is 96.4 kilojoules

00:08:08.600 --> 00:08:11.340
per mole times volts.

00:08:11.340 --> 00:08:13.650
If you do the math,
or as we say at MIT,

00:08:13.650 --> 00:08:15.960
plug and chug, what
you find out is

00:08:15.960 --> 00:08:18.950
that the free energy change of
the reaction that's written,

00:08:18.950 --> 00:08:25.500
the NADH oxidation reaction, is
minus 220 kilojoules per mole.

00:08:25.500 --> 00:08:29.100
This number is negative and that
means the reaction is favorable

00:08:29.100 --> 00:08:31.520
as drawn.

00:08:31.520 --> 00:08:35.090
That is, the reaction
goes from left to right.

00:08:35.090 --> 00:08:37.940
The 220 kilojoules is
the amount of energy

00:08:37.940 --> 00:08:40.580
that's available for the
three purposes of the pathway.

00:08:40.580 --> 00:08:47.140
That is, ATP synthesis, heat
generation, or movement.

00:08:47.140 --> 00:08:51.910
If we were going to make ATP,
we would divide 220 by 32,

00:08:51.910 --> 00:08:54.670
because we get about
32 kilojoules of energy

00:08:54.670 --> 00:08:57.855
by hydrolysis of ATP,
and we can calculate

00:08:57.855 --> 00:08:59.230
that we're going
to get something

00:08:59.230 --> 00:09:03.400
in the order of about 3
ATPs for every NADH that

00:09:03.400 --> 00:09:07.560
gives up two electrons to
the electron transport chain.

00:09:07.560 --> 00:09:10.740
We could easily do the same
oxidation reaction and study

00:09:10.740 --> 00:09:13.890
FADH2, but in this
case, we would calculate

00:09:13.890 --> 00:09:17.280
that we would get actually less
energy, because the oxidation

00:09:17.280 --> 00:09:21.330
potential of flavins, as
compared to NAD, is different.

00:09:21.330 --> 00:09:24.780
In that case, that
is, FADH2 oxidation,

00:09:24.780 --> 00:09:28.950
you would get only about
two ATPs per FADH2 oxidized.

00:09:28.950 --> 00:09:32.960
So the FADH2 produced in
the succinate dehydrogenase

00:09:32.960 --> 00:09:35.550
step of the TCA
cycle is less energy

00:09:35.550 --> 00:09:38.760
yielding than, for example,
the oxidation of malate

00:09:38.760 --> 00:09:43.850
to oxaloacetate that occurs
later in the pathway.

00:09:43.850 --> 00:09:46.150
Let's turn now to storyboard 13.

00:09:46.150 --> 00:09:49.100
We now have an idea of
the rough amount of energy

00:09:49.100 --> 00:09:52.870
that's going to be generated
by nutrient oxidation.

00:09:52.870 --> 00:09:54.910
Next we're going to
look a little bit more

00:09:54.910 --> 00:09:57.700
in detail at the mechanism
by which the electrons are

00:09:57.700 --> 00:10:00.550
transported from the
reduced substances

00:10:00.550 --> 00:10:04.840
that constitute our electron
donors, NADH and FADH2,

00:10:04.840 --> 00:10:08.830
to molecular oxygen, or
whatever the terminal electron

00:10:08.830 --> 00:10:12.920
acceptor is in the biological
system under study.

00:10:12.920 --> 00:10:15.380
As was seen, the
electron transfer

00:10:15.380 --> 00:10:18.620
process that we've been
studying liberates energy,

00:10:18.620 --> 00:10:21.290
and that energy is going to
be used to power pumps that

00:10:21.290 --> 00:10:25.520
will transport protons from
the matrix of the mitochondrian

00:10:25.520 --> 00:10:29.300
out into the intermembrane space
between the mitochondrial inner

00:10:29.300 --> 00:10:31.400
and outer membranes.

00:10:31.400 --> 00:10:32.870
In the case of
electron transport

00:10:32.870 --> 00:10:35.660
with the goal of ATP
synthesis, the protons

00:10:35.660 --> 00:10:38.360
that are generated in
the intermembrane space

00:10:38.360 --> 00:10:40.640
will be allowed to flow
back through a device

00:10:40.640 --> 00:10:42.620
that mechanically
couples motion--

00:10:42.620 --> 00:10:44.600
that is the spinning
of a shaft--

00:10:44.600 --> 00:10:47.660
to drive conformational
changes in enzymes

00:10:47.660 --> 00:10:51.500
that will allow the otherwise
endergonic synthesis of ATP

00:10:51.500 --> 00:10:54.800
from ADP in inorganic phosphate.

00:10:54.800 --> 00:10:58.900
That machine is called
the ATP synthase.

00:10:58.900 --> 00:11:00.970
Let's look at
panel A. This panel

00:11:00.970 --> 00:11:04.150
shows the details of the
electron transport system.

00:11:04.150 --> 00:11:05.809
It looks a little
bit complicated,

00:11:05.809 --> 00:11:08.350
but let's not lose sight of the
fact that what it's all about

00:11:08.350 --> 00:11:12.280
is powering pumps,
pumps that pump protons.

00:11:12.280 --> 00:11:14.020
In the lower left
of the panel we

00:11:14.020 --> 00:11:18.340
see the TCA cycle
generating NADH and FADH2.

00:11:18.340 --> 00:11:22.270
The NADH approaches complex
one of the mitochondrial inner

00:11:22.270 --> 00:11:24.270
membrane.

00:11:24.270 --> 00:11:29.310
Complex one is in an NADH
dehydrogenase enzyme.

00:11:29.310 --> 00:11:31.980
The enzyme has a flavin
that accepts the electrons

00:11:31.980 --> 00:11:36.090
from NADH, passes them along
to iron sulfur centers,

00:11:36.090 --> 00:11:38.064
and then to a variety
of cytochromes.

00:11:38.064 --> 00:11:40.230
It moves the electrons up
to the point where they're

00:11:40.230 --> 00:11:42.000
going to be
transferred to coenzyme

00:11:42.000 --> 00:11:45.270
Q. In its oxidized
form, coenzyme Q

00:11:45.270 --> 00:11:47.370
binds to complex one.

00:11:47.370 --> 00:11:49.650
The oxidized form
of coenzyme Q will

00:11:49.650 --> 00:11:52.140
be reduced first
to a semiquinone

00:11:52.140 --> 00:11:55.380
and then to a hydroquinone,
which are located, as shown,

00:11:55.380 --> 00:11:58.710
inside the mitochondrial
inner membrane.

00:11:58.710 --> 00:12:01.110
We usually draw them
as being free floating

00:12:01.110 --> 00:12:04.440
within the membrane, but
that's probably inaccurate.

00:12:04.440 --> 00:12:06.270
These co-factors
are probably bound

00:12:06.270 --> 00:12:10.140
to physical entities inside the
mitochondrial inner membrane.

00:12:10.140 --> 00:12:14.430
The picture also shows FADH2
from the TCA cycle interacting

00:12:14.430 --> 00:12:17.430
with complex two, which is
a flavin containing enzyme,

00:12:17.430 --> 00:12:20.010
and it will also
transfer its electrons

00:12:20.010 --> 00:12:22.230
to the oxidized
form of coenzyme Q,

00:12:22.230 --> 00:12:25.190
ultimately to create
the reduced coenzyme

00:12:25.190 --> 00:12:28.590
QH2 which is the hydroquinone.

00:12:28.590 --> 00:12:31.520
Just as a point of
reference to the TCA cycle,

00:12:31.520 --> 00:12:35.900
complex two is also known
as succinate dehydrogenase.

00:12:35.900 --> 00:12:38.780
We haven't done fatty
acid oxidation yet,

00:12:38.780 --> 00:12:41.300
but there's a step in
fatty acid oxidation

00:12:41.300 --> 00:12:45.050
in which an alkane is
converted to an alkene.

00:12:45.050 --> 00:12:47.360
The electrons from
that oxidation reaction

00:12:47.360 --> 00:12:50.810
go through a flavin
protein called ETF-pre,

00:12:50.810 --> 00:12:54.770
for electron transferring
flavor protein, and once again

00:12:54.770 --> 00:12:57.320
those electrons
flow into coenzyme Q

00:12:57.320 --> 00:13:01.230
to form the reduced
form of coenzyme Q.

00:13:01.230 --> 00:13:04.470
Remember when we talked about
the glycerol three phosphate

00:13:04.470 --> 00:13:05.120
shuttle?

00:13:05.120 --> 00:13:07.350
I mentioned that there's
a mitochondrial membrane

00:13:07.350 --> 00:13:11.280
associated glycerol three
phosphate dehydrogenase.

00:13:11.280 --> 00:13:14.490
You can see that enzyme at the
top part of the inner membrane

00:13:14.490 --> 00:13:16.010
as I've drawn it.

00:13:16.010 --> 00:13:18.150
And once again,
flavin in that enzyme

00:13:18.150 --> 00:13:20.730
will carry the electrons
into coenzyme Q,

00:13:20.730 --> 00:13:25.300
generating reduced form
of the co-factor QH2.

00:13:25.300 --> 00:13:27.520
The left part of this
picture pretty neatly

00:13:27.520 --> 00:13:31.870
shows how nutrient oxidation
can channel the electrons

00:13:31.870 --> 00:13:34.240
into a common mobile
electron carrier,

00:13:34.240 --> 00:13:37.000
coenzyme Q. Lots
of different fuels

00:13:37.000 --> 00:13:41.130
give up their electrons to
a common electron carrier.

00:13:41.130 --> 00:13:43.840
The hydroquinone QH2
will then go and interact

00:13:43.840 --> 00:13:47.250
with complex three of the
electron transport chain.

00:13:47.250 --> 00:13:49.990
In complex three, electrons
will be transported

00:13:49.990 --> 00:13:52.960
through a number of different
electron relay stations

00:13:52.960 --> 00:13:55.900
and ultimately be picked
up by cytochrome C, which

00:13:55.900 --> 00:13:59.750
is initially in its plus
three oxidation state.

00:13:59.750 --> 00:14:02.740
Cytochrome C is reduced
by the single electron

00:14:02.740 --> 00:14:04.870
coming through complex three.

00:14:04.870 --> 00:14:09.520
In this process its iron is
reduced to its plus two state.

00:14:09.520 --> 00:14:11.980
This electron on
cytochrome C then

00:14:11.980 --> 00:14:14.710
migrates across
the outer surface

00:14:14.710 --> 00:14:16.930
of the inner membrane
of the mitochondrian

00:14:16.930 --> 00:14:19.630
to interact with complex four.

00:14:19.630 --> 00:14:21.430
When it interacts
with complex four,

00:14:21.430 --> 00:14:24.910
the reduced form cytochrome
C gives up its electron

00:14:24.910 --> 00:14:27.370
to a copper residue
on the copper

00:14:27.370 --> 00:14:31.910
A subunit of complex four.

00:14:31.910 --> 00:14:35.810
In the figure, this
complex is called CuA.

00:14:35.810 --> 00:14:40.560
the more common name for complex
four is cytochrome C oxidase.

00:14:40.560 --> 00:14:45.180
So cytochrome c oxidase
oxidizes is the iron back

00:14:45.180 --> 00:14:49.590
to its iron three oxidation
state, then cytochrome C

00:14:49.590 --> 00:14:52.050
migrates back to
complex three where

00:14:52.050 --> 00:14:54.910
it's able to pick
up another electron.

00:14:54.910 --> 00:14:58.390
We can think of cytochrome C as
a mobile electron carrier that

00:14:58.390 --> 00:15:01.420
shuttles an electron
along the inner surface

00:15:01.420 --> 00:15:04.790
of the mitochondrial
inner membrane.

00:15:04.790 --> 00:15:08.150
Looking back at complex four,
or cytochrome C oxidase,

00:15:08.150 --> 00:15:11.480
the electrons are
passed from cytochrome A

00:15:11.480 --> 00:15:13.550
to a series of other
electron carriers,

00:15:13.550 --> 00:15:16.700
and ultimately they flow
into molecular oxygen.

00:15:16.700 --> 00:15:20.250
Molecular oxygen is anchored
on one side to heme A3

00:15:20.250 --> 00:15:23.110
and on the other
side to copper B.

00:15:23.110 --> 00:15:26.470
Oxygen undergoes a four
electron reduction and picks

00:15:26.470 --> 00:15:30.910
up four protons along the way
to form two molecules of water.

00:15:30.910 --> 00:15:34.150
If the electrons started with
NADH and ends up in oxygen

00:15:34.150 --> 00:15:37.690
to form water, you get
220 kilojoules of energy.

00:15:37.690 --> 00:15:39.440
And as I said, you
get somewhat less

00:15:39.440 --> 00:15:42.910
of your electrons started
out as a reduced flavin.

00:15:42.910 --> 00:15:45.070
Now let's look at
panel B. I want

00:15:45.070 --> 00:15:47.920
to say a few words at the
outset about proton pumps,

00:15:47.920 --> 00:15:51.220
keeping in mind that the
reason electrons were moved

00:15:51.220 --> 00:15:55.330
through the electron transport
chain was to power these pumps.

00:15:55.330 --> 00:15:59.080
In the lower left part of the
figure, we can see complex one.

00:15:59.080 --> 00:16:03.070
The transit of electrons
through complex one from NADH

00:16:03.070 --> 00:16:05.830
results in the transport
of four protons

00:16:05.830 --> 00:16:09.610
from the mitochondrial matrix
into the intermembrane space.

00:16:09.610 --> 00:16:13.330
That is, two electrons
from NADH are transported,

00:16:13.330 --> 00:16:15.700
and coincident with
that, four protons

00:16:15.700 --> 00:16:19.060
are pumped into the
intermembrane space.

00:16:19.060 --> 00:16:20.740
Later we'll see
that complex three

00:16:20.740 --> 00:16:23.530
is the location of something
called the Q cycle.

00:16:23.530 --> 00:16:25.660
I'm going to cover
the proton pumping

00:16:25.660 --> 00:16:28.450
properties of the Q
cycle in some detail

00:16:28.450 --> 00:16:30.400
in the next storyboard.

00:16:30.400 --> 00:16:32.620
The passage of
those two electrons

00:16:32.620 --> 00:16:35.710
through complex three
results in the transport

00:16:35.710 --> 00:16:40.960
of an additional four protons
into the intermembrane space.

00:16:40.960 --> 00:16:44.320
Lastly, the transit of
electrons through complex four,

00:16:44.320 --> 00:16:46.660
the cytochrome C
oxidase, results

00:16:46.660 --> 00:16:48.820
in the transport of
another two protons

00:16:48.820 --> 00:16:51.750
into the intermembrane space.

00:16:51.750 --> 00:16:55.050
Now let's look at panel
C. Adding things up,

00:16:55.050 --> 00:16:56.820
if we start with
two electrons coming

00:16:56.820 --> 00:17:00.270
from NADH we transport
about 10 protons

00:17:00.270 --> 00:17:01.530
into the intermembrane space.

00:17:01.530 --> 00:17:05.880
That's enough to make about
three molecules of ATP.

00:17:05.880 --> 00:17:09.359
If our electrons start
with FADH2 reduced flavin,

00:17:09.359 --> 00:17:12.230
we only transport
about six protons.

00:17:12.230 --> 00:17:14.550
That's enough to make two ATPs.

00:17:14.550 --> 00:17:17.490
If you remember, making ATP
is only one of the things

00:17:17.490 --> 00:17:20.430
that we can do with the
power of the proton gradient.

00:17:20.430 --> 00:17:22.140
I mentioned earlier
that we can also use

00:17:22.140 --> 00:17:24.800
it to generate heat and motion.

00:17:24.800 --> 00:17:27.140
Let me talk for a
minute about why one

00:17:27.140 --> 00:17:29.060
would want to generate heat.

00:17:29.060 --> 00:17:31.160
Newborn babies are
like small balls.

00:17:31.160 --> 00:17:34.410
They have a high
surface to volume ratio.

00:17:34.410 --> 00:17:36.320
Their high surface
to volume ratio

00:17:36.320 --> 00:17:39.090
makes heat loss a very
significant reality,

00:17:39.090 --> 00:17:41.690
and, in fact, a problem
for the newborn.

00:17:41.690 --> 00:17:44.390
They have, therefore,
specialized mitochondria

00:17:44.390 --> 00:17:47.600
in their neck in an
area called brown fat.

00:17:47.600 --> 00:17:50.630
The fat is brown because it
is loaded with highly colored

00:17:50.630 --> 00:17:51.950
mitochondria.

00:17:51.950 --> 00:17:53.870
These mitochondria
have a protein

00:17:53.870 --> 00:17:57.650
that enables the protons pumped
into the intermembrane space

00:17:57.650 --> 00:18:00.950
to flow back freely into
the mitochondrial matrix

00:18:00.950 --> 00:18:02.840
with the generation of heat.

00:18:02.840 --> 00:18:06.530
That is, they don't make ATP in
the brown fat, they make heat.

00:18:06.530 --> 00:18:09.680
This helps promote thermal
regulation in the baby.

00:18:09.680 --> 00:18:11.780
This is also the
mechanism by which

00:18:11.780 --> 00:18:14.240
hibernating animals,
such as a bear,

00:18:14.240 --> 00:18:16.790
can maintain body
temperature during the winter

00:18:16.790 --> 00:18:19.440
when the bear is hibernating.

00:18:19.440 --> 00:18:22.200
This process overall
is called uncoupling

00:18:22.200 --> 00:18:24.690
of electron transport,
from the process

00:18:24.690 --> 00:18:27.300
that we're going to be
looking at next, oxidative

00:18:27.300 --> 00:18:28.470
phosphorylation.

00:18:28.470 --> 00:18:31.830
Oxidative phosphorylation
is the process by which

00:18:31.830 --> 00:18:35.180
we're going to be making ATP.

00:18:35.180 --> 00:18:37.730
Uncoupling is also
a process used

00:18:37.730 --> 00:18:40.070
by some flowers
that have to come up

00:18:40.070 --> 00:18:42.500
through frozen ground
in the springtime.

00:18:42.500 --> 00:18:45.170
For example, the skunk
cabbage and the crocus

00:18:45.170 --> 00:18:47.960
are very good at uncoupling
electron transport

00:18:47.960 --> 00:18:50.180
from oxidative phosphorylation.

00:18:50.180 --> 00:18:53.090
They let the protons in
the proton gradient flow

00:18:53.090 --> 00:18:55.370
back across the
mitochondrial inner membrane,

00:18:55.370 --> 00:18:58.520
and by doing so these
plants are able to generate

00:18:58.520 --> 00:19:00.620
heat that will
allow them to grow

00:19:00.620 --> 00:19:02.630
at subfreezing temperatures.

00:19:02.630 --> 00:19:07.020
In other words, the plant
itself becomes a little heater.

00:19:07.020 --> 00:19:08.850
At this point, let me
give you a little bit

00:19:08.850 --> 00:19:12.120
of a preview of how we use
this proton gradient in order

00:19:12.120 --> 00:19:13.890
to synthesize ATP.

00:19:13.890 --> 00:19:15.750
As we have seen, it
took energy in order

00:19:15.750 --> 00:19:19.170
to create a gradient in
which there are protons

00:19:19.170 --> 00:19:22.980
in the intermembrane space, and
protons are chemical entities,

00:19:22.980 --> 00:19:25.770
so we've created a
chemical gradient.

00:19:25.770 --> 00:19:29.190
But also, we're putting a
very high positive charge

00:19:29.190 --> 00:19:32.640
density in the small,
enclosed intermembrane space.

00:19:32.640 --> 00:19:36.450
So we have also created an
electrochemical gradient.

00:19:36.450 --> 00:19:39.960
It is the release of those
gradients that empowers

00:19:39.960 --> 00:19:42.420
many of our vital processes.

00:19:42.420 --> 00:19:46.350
For a final comment please see
panel D. Peter Mitchell figured

00:19:46.350 --> 00:19:49.230
out how the energy in that
electrochemical gradient

00:19:49.230 --> 00:19:51.510
could be released and
converted into the energy

00:19:51.510 --> 00:19:53.640
it takes to make chemical bonds.

00:19:53.640 --> 00:19:56.070
Mitchell's conclusions
serve as the basis

00:19:56.070 --> 00:19:58.230
of what is called the
chemiosmotic coupling

00:19:58.230 --> 00:20:02.870
hypothesis, and we'll be looking
at that in some detail later.