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CATHERINE DRENNAN:
And now I just want

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to revisit-- when we
started the unit we listed

00:00:30.450 --> 00:00:33.340
a bunch of things that
affected the rates of reaction,

00:00:33.340 --> 00:00:35.040
and we see where we are.

00:00:35.040 --> 00:00:36.980
We've talked about mechanism.

00:00:36.980 --> 00:00:39.780
We've talked about the
nature of the material,

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The Arrhenius constant depends
on the nature of the material,

00:00:43.330 --> 00:00:45.300
the activation energy
barrier depends

00:00:45.300 --> 00:00:48.650
on the nature of the
reactants of the material.

00:00:48.650 --> 00:00:51.480
Concentrations and
pressure-- partial pressures,

00:00:51.480 --> 00:00:52.770
temperatures.

00:00:52.770 --> 00:00:55.540
The only thing we haven't
talked about are catalysts.

00:00:55.540 --> 00:00:57.700
So that's what we're
going to focus on today.

00:00:57.700 --> 00:01:00.020
We're going to learn
about catalysts and how

00:01:00.020 --> 00:01:03.750
they affect kinetics.

00:01:03.750 --> 00:01:05.840
So a catalyst, this
is something that's

00:01:05.840 --> 00:01:09.300
used by non-scientists,
a lot of laymen talk

00:01:09.300 --> 00:01:12.010
about catalyzing something.

00:01:12.010 --> 00:01:16.620
There's many companies
with a name catalyst in it.

00:01:16.620 --> 00:01:18.590
So a catalyst is
a substance-- this

00:01:18.590 --> 00:01:23.910
is its technical definition--
that will speed up a reaction,

00:01:23.910 --> 00:01:27.430
but it is not, itself,
consumed by the reaction.

00:01:27.430 --> 00:01:30.000
It doesn't undergo
any permanent change.

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So it can be thought of a sort
of a helping hand, a lift up.

00:01:34.370 --> 00:01:37.990
It makes the reaction go faster.

00:01:37.990 --> 00:01:41.780
But it does not appear in the
overall balanced equation,

00:01:41.780 --> 00:01:44.560
because it's not
being transformed,

00:01:44.560 --> 00:01:47.080
it's not being converted
to something else.

00:01:47.080 --> 00:01:50.900
It's just speeding
up the reaction.

00:01:50.900 --> 00:01:56.390
OK so now let's go back to our
reaction coordinate diagrams

00:01:56.390 --> 00:02:00.030
and think about what
a catalyst is doing.

00:02:00.030 --> 00:02:05.610
So back again, potential energy
vs. the reaction coordinate.

00:02:05.610 --> 00:02:08.860
We have the potential energy
of our reactants up here,

00:02:08.860 --> 00:02:12.970
potential energy of our products
here, delta E, the difference

00:02:12.970 --> 00:02:14.280
between them.

00:02:14.280 --> 00:02:17.780
But again, before the
reactants can go onto products,

00:02:17.780 --> 00:02:21.630
they must overcome an
activation energy barrier.

00:02:21.630 --> 00:02:25.040
So EA for the forward direction.

00:02:25.040 --> 00:02:27.860
And if they're going from
products to reactants,

00:02:27.860 --> 00:02:30.320
they don't have to
just do that, they

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have to go way up here first.

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And this is the
activation energy barrier

00:02:36.230 --> 00:02:39.540
without a catalyst, the
transition state, the activated

00:02:39.540 --> 00:02:40.630
complex.

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That's the height to
which the molecules

00:02:43.780 --> 00:02:47.990
need to get in potential energy
to be able to react and go on.

00:02:47.990 --> 00:02:50.250
So we can draw now our curve.

00:02:50.250 --> 00:02:54.530
So from reactants we go
up, overcome that barrier,

00:02:54.530 --> 00:02:58.250
reach this state, and
then can go onto products.

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So they come together,
and you end up

00:03:00.510 --> 00:03:02.910
at a lower potential
energy in this case.

00:03:02.910 --> 00:03:05.070
But before you get
there, you have

00:03:05.070 --> 00:03:07.700
to overcome this
activation energy barrier.

00:03:07.700 --> 00:03:08.200
OK.

00:03:08.200 --> 00:03:10.940
So this is the diagram
we've seen before.

00:03:10.940 --> 00:03:13.740
What is the catalyst doing?

00:03:13.740 --> 00:03:18.950
So what the catalyst does is
it decreases this barrier.

00:03:18.950 --> 00:03:24.720
So now we have a dashed line
for the barrier with a catalyst,

00:03:24.720 --> 00:03:27.930
and we can draw a
new curve over here

00:03:27.930 --> 00:03:30.400
so you don't have
to get as high,

00:03:30.400 --> 00:03:35.230
you don't have as large
a barrier anymore.

00:03:35.230 --> 00:03:38.010
And we can put in
the new barriers.

00:03:38.010 --> 00:03:41.680
So in dashed lines now we have
the activation energy barrier

00:03:41.680 --> 00:03:46.620
for the forward direction, and
the activation energy barrier

00:03:46.620 --> 00:03:48.280
for the reverse direction.

00:03:48.280 --> 00:03:50.570
Both of them are less.

00:03:50.570 --> 00:03:52.950
This line is below.

00:03:52.950 --> 00:03:57.440
The catalyst has lowered the
activation energy barrier.

00:03:57.440 --> 00:04:00.230
They typically act by
reducing the barrier,

00:04:00.230 --> 00:04:06.730
both for the forward direction
and the reverse direction.

00:04:06.730 --> 00:04:11.450
So we can also say-- and people
do-- that catalysts stabilize

00:04:11.450 --> 00:04:15.180
or lower the energy of
this transition state,

00:04:15.180 --> 00:04:17.760
also known as the
activated complex.

00:04:17.760 --> 00:04:22.220
So they bring this down,
they lower the energy needed.

00:04:22.220 --> 00:04:26.440
It's easier to get over the
hump when you have a catalyst

00:04:26.440 --> 00:04:30.950
and therefore it
speeds up the reaction.

00:04:30.950 --> 00:04:35.000
So catalysts have no effect
on the thermodynamics

00:04:35.000 --> 00:04:36.160
of the system.

00:04:36.160 --> 00:04:39.510
They're affecting the
kinetics of the system,

00:04:39.510 --> 00:04:44.040
and this is because free
energy, our friend delta G,

00:04:44.040 --> 00:04:45.230
is a state function.

00:04:45.230 --> 00:04:47.290
It's independent of path.

00:04:47.290 --> 00:04:49.880
OK with these things
in mind, tell me

00:04:49.880 --> 00:04:53.840
with a clicker question what
happens to the equilibrium

00:04:53.840 --> 00:04:58.470
constant if you have
a catalyst present?

00:05:13.560 --> 00:05:14.060
All right.

00:05:14.060 --> 00:05:15.010
10 more seconds.

00:05:31.300 --> 00:05:32.320
And that is true.

00:05:32.320 --> 00:05:35.020
It is not changed.

00:05:35.020 --> 00:05:38.180
So the equilibrium
constant is not

00:05:38.180 --> 00:05:41.380
changed by the
presence of a catalyst

00:05:41.380 --> 00:05:44.900
because this is a
thermodynamic property.

00:05:44.900 --> 00:05:48.590
So delta G is not changed,
and the equilibrium constant

00:05:48.590 --> 00:05:49.740
is not changed.

00:05:49.740 --> 00:05:53.590
So it doesn't depend on path,
and this is a path difference.

00:05:53.590 --> 00:05:56.700
The catalyst changes
the path, but it

00:05:56.700 --> 00:06:00.130
doesn't change the beginning
state or the end state.

00:06:00.130 --> 00:06:02.780
And so just to help
you remember this,

00:06:02.780 --> 00:06:06.330
I'll give you a little
trick to remember this.

00:06:06.330 --> 00:06:08.570
So again, catalysts
effect the kinetics,

00:06:08.570 --> 00:06:09.980
not the thermodynamics.

00:06:09.980 --> 00:06:14.220
And one way to remember this
is that the Chinese symbol

00:06:14.220 --> 00:06:17.980
for catalysts and marriage
broker are the same.

00:06:17.980 --> 00:06:21.180
So a marriage broker
increases the rate

00:06:21.180 --> 00:06:24.080
at which a couple comes
together, usually introduces

00:06:24.080 --> 00:06:26.070
the two people to each other.

00:06:26.070 --> 00:06:29.070
Of course online services
can do this as well,

00:06:29.070 --> 00:06:34.260
but none of these things
can make a couple stable

00:06:34.260 --> 00:06:36.920
if the couple is not stable.

00:06:36.920 --> 00:06:40.430
So online dating services,
marriage brokers,

00:06:40.430 --> 00:06:44.370
increase the kinetics, increase
the rate at which people meet,

00:06:44.370 --> 00:06:47.730
increase the
encounter, but do not

00:06:47.730 --> 00:06:50.600
change the thermodynamics
of the relationship.

00:06:50.600 --> 00:06:54.140
A couple is stable or
unstable regardless

00:06:54.140 --> 00:06:57.400
of the marriage broker,
regardless of the catalyst.

00:06:57.400 --> 00:07:02.320
So affects kinetics,
not thermodynamics.

00:07:02.320 --> 00:07:08.250
All right, so there are two
major types of catalysts,

00:07:08.250 --> 00:07:10.880
homogeneous
catalysts-- and that is

00:07:10.880 --> 00:07:13.370
just when the catalyst
and the reactants

00:07:13.370 --> 00:07:15.360
are in the same phase.

00:07:15.360 --> 00:07:18.640
An example that has actually
been in the news a bit

00:07:18.640 --> 00:07:23.210
this fall is the
ozone layer, depletion

00:07:23.210 --> 00:07:26.970
of the ozone by
chlorofluorocarbons,

00:07:26.970 --> 00:07:28.310
all in the gas phase.

00:07:28.310 --> 00:07:32.930
So this would be the
catalyst for the depletion

00:07:32.930 --> 00:07:35.570
is in the same phase as
the thing it's depleting.

00:07:35.570 --> 00:07:38.430
And here's a little
picture of the increase

00:07:38.430 --> 00:07:40.650
in the ozone hole over time.

00:07:40.650 --> 00:07:42.820
But there was some
good news this fall

00:07:42.820 --> 00:07:45.040
that it seemed like
the rate of increase

00:07:45.040 --> 00:07:48.030
was not as dramatic, that
it was staying a little bit

00:07:48.030 --> 00:07:51.160
more level, which is
exciting to know that if we

00:07:51.160 --> 00:07:55.620
stop bad behavior,
that we can and we

00:07:55.620 --> 00:07:57.220
can have a positive effect.

00:07:57.220 --> 00:08:00.315
So we shouldn't just say, oh,
we polluted so much already,

00:08:00.315 --> 00:08:01.190
what's a little more?

00:08:01.190 --> 00:08:03.660
We've already done
all the damage.

00:08:03.660 --> 00:08:04.630
There's no point.

00:08:04.630 --> 00:08:06.190
No, no there is a point.

00:08:06.190 --> 00:08:09.560
If we stop doing damage,
good thing-- better things

00:08:09.560 --> 00:08:10.280
will happen.

00:08:10.280 --> 00:08:12.820
So that was some
good news that people

00:08:12.820 --> 00:08:14.880
were hearing about this fall.

00:08:14.880 --> 00:08:20.640
OK along the pollution lines
of destroying our planet,

00:08:20.640 --> 00:08:25.170
there's also heterogeneous
catalyst, so a different phase.

00:08:25.170 --> 00:08:28.620
And a common example of this
is the catalytic converter

00:08:28.620 --> 00:08:29.980
in a car.

00:08:29.980 --> 00:08:35.020
And so catalytic converters
use of metals, solid phase

00:08:35.020 --> 00:08:38.030
to help catalyze
reactions of gases,

00:08:38.030 --> 00:08:40.650
so solid gas, different phase.

00:08:40.650 --> 00:08:42.669
And they try to
convert these gases

00:08:42.669 --> 00:08:47.570
to last less toxic pollutants.

00:08:47.570 --> 00:08:49.710
And so I'll just give
you a little example

00:08:49.710 --> 00:08:51.230
of how this could work.

00:08:51.230 --> 00:08:53.230
I'm not a catalytic
converter, but just

00:08:53.230 --> 00:08:56.780
in general with this little
movie-- so we have this metal

00:08:56.780 --> 00:08:58.250
surface here.

00:08:58.250 --> 00:09:02.410
And the metal surface
will absorb H2 gas

00:09:02.410 --> 00:09:04.790
and help to dissociate H2.

00:09:04.790 --> 00:09:08.060
So here's a hydrogen,
here's a hydrogen absorbed

00:09:08.060 --> 00:09:09.790
onto this metal surface.

00:09:09.790 --> 00:09:13.710
And then you can flow something
over the metal surface,

00:09:13.710 --> 00:09:17.440
and that will be reduced
by the hydrogens.

00:09:17.440 --> 00:09:21.490
So let me get this to go.

00:09:21.490 --> 00:09:25.210
So here we see,
now the hydrogens

00:09:25.210 --> 00:09:30.980
are popping off and going
to reduce ethene over here.

00:09:30.980 --> 00:09:34.820
So this is an example of a
heterogeneous catalyst, where

00:09:34.820 --> 00:09:37.380
we have metal in a
solid phase that's

00:09:37.380 --> 00:09:41.110
catalyzing a reaction
that involves materials

00:09:41.110 --> 00:09:42.930
in a different phase.

00:09:42.930 --> 00:09:45.420
OK so two types.

00:09:45.420 --> 00:09:49.410
But there is also my
very, very favorite type,

00:09:49.410 --> 00:09:52.610
which is enzymes.

00:09:52.610 --> 00:09:54.390
So we're going to
talk just briefly

00:09:54.390 --> 00:09:58.380
about enzyme catalysis,
which will give you a leg

00:09:58.380 --> 00:10:01.470
up when you go on to
courses that have something

00:10:01.470 --> 00:10:03.990
to do with biochemistry.

00:10:03.990 --> 00:10:08.630
And these days biochemistry is
sort of everywhere on campus.

00:10:08.630 --> 00:10:10.590
You might think I
can escape biology

00:10:10.590 --> 00:10:11.970
to go into chemical engineering.

00:10:11.970 --> 00:10:13.879
No, no you can't.

00:10:13.879 --> 00:10:15.420
There are a lot of
chemical engineers

00:10:15.420 --> 00:10:17.700
that are working
only with enzymes.

00:10:17.700 --> 00:10:21.940
So a little bit about
enzymes as catalysts.

00:10:21.940 --> 00:10:26.910
So enzymes, large
protein molecules,

00:10:26.910 --> 00:10:29.230
20,000 grams per mole or more.

00:10:29.230 --> 00:10:30.950
That's a tiny protein.

00:10:30.950 --> 00:10:32.570
And they're made
up of amino acids,

00:10:32.570 --> 00:10:34.970
and you've seen a lot of
amino acids in this class.

00:10:34.970 --> 00:10:39.000
We've been using those
to think about PKA's.

00:10:39.000 --> 00:10:42.380
And so here we have an
amino acid with a sidechain,

00:10:42.380 --> 00:10:45.260
it's abbreviated R.
There's 20 different R's,

00:10:45.260 --> 00:10:47.330
20 different amino acids.

00:10:47.330 --> 00:10:51.700
And amino acids come together
forming peptide bonds,

00:10:51.700 --> 00:10:54.690
where we have a connection
between this carbonyl

00:10:54.690 --> 00:10:57.570
and the nitrogen of
the next amino acid.

00:10:57.570 --> 00:11:02.740
So amino acid one amino acid
two and here's the peptide bond.

00:11:02.740 --> 00:11:07.220
These then form long
chains, and will fold up

00:11:07.220 --> 00:11:09.610
into a compact structure.

00:11:09.610 --> 00:11:14.060
So here is an example of
a structure of an enzyme.

00:11:14.060 --> 00:11:17.220
And I'll just tell you a
little bit about this enzyme.

00:11:17.220 --> 00:11:20.840
So here there are four
polypeptide chains, so one

00:11:20.840 --> 00:11:24.250
in green, one in red, one
in yellow, and one in blue.

00:11:24.250 --> 00:11:27.030
And they form this
compact structure.

00:11:27.030 --> 00:11:30.040
And this picture
shows these ribbons.

00:11:30.040 --> 00:11:33.980
Here is alpha helices,
there's squiggly, the arrows,

00:11:33.980 --> 00:11:35.480
or beta strands.

00:11:35.480 --> 00:11:38.200
And so they draw ribbons through
the alpha carbon position,

00:11:38.200 --> 00:11:39.800
so you don't see
all the atoms here

00:11:39.800 --> 00:11:43.370
you just kind of see how the
chains wrap around each other

00:11:43.370 --> 00:11:46.800
to form this overall
protein structure.

00:11:46.800 --> 00:11:52.150
So this particular enzyme
catalyzes the last step

00:11:52.150 --> 00:11:55.720
in the biosynthesis of
an antibiotic fosfomycin.

00:11:55.720 --> 00:11:59.060
So it converts this reactant
or substrate molecule

00:11:59.060 --> 00:12:02.030
into the fosfomycin antibiotic.

00:12:02.030 --> 00:12:05.230
Fosfomycin is used in
combination therapy

00:12:05.230 --> 00:12:08.490
to treat MRSA infections.

00:12:08.490 --> 00:12:10.630
So I have always
tried to give you

00:12:10.630 --> 00:12:13.130
examples of important
areas of science

00:12:13.130 --> 00:12:17.110
that smart people should go
into and solve these problems,

00:12:17.110 --> 00:12:20.570
and I'll just mention antibiotic
resistance with this figure.

00:12:20.570 --> 00:12:22.720
This was published in
the journal Nature.

00:12:22.720 --> 00:12:25.350
They called it a perfect
storm, because here we

00:12:25.350 --> 00:12:29.830
see the increase in
antibiotic resistant strains.

00:12:29.830 --> 00:12:31.260
This is MRSA here.

00:12:31.260 --> 00:12:33.970
Up to 60% over here.

00:12:33.970 --> 00:12:36.730
And these are--
this data is old.

00:12:36.730 --> 00:12:40.490
And then that go up, and
here in blue going down

00:12:40.490 --> 00:12:44.230
are the new antibiotics that
have been approved for use.

00:12:44.230 --> 00:12:48.030
So we have much more
resistance and many fewer

00:12:48.030 --> 00:12:50.320
antibiotics being approved.

00:12:50.320 --> 00:12:53.570
And so this what has been
called the perfect storm,

00:12:53.570 --> 00:12:57.520
and this situation
the y data here 2010.

00:12:57.520 --> 00:12:58.790
It's not any better.

00:12:58.790 --> 00:13:02.830
In fact, it's worse now, so one
important area is to come up

00:13:02.830 --> 00:13:05.170
with new antibiotics.

00:13:05.170 --> 00:13:09.640
All right so many of the targets
of antibiotics are enzymes.

00:13:09.640 --> 00:13:13.360
Many of the ways to make
antibiotics is using enzymes,

00:13:13.360 --> 00:13:18.000
and so enzyme catalysis is
very important for medicine,

00:13:18.000 --> 00:13:20.950
and also for engineering
and biofuels.

00:13:20.950 --> 00:13:23.370
And people are using enzymes
for pretty much everything

00:13:23.370 --> 00:13:24.490
these days.

00:13:24.490 --> 00:13:24.990
All right.

00:13:24.990 --> 00:13:28.310
So a couple of
terminology-- reactants.

00:13:28.310 --> 00:13:29.820
We've been talking
about reactants.

00:13:29.820 --> 00:13:32.330
If it's an enzyme, it's
called a substrate.

00:13:32.330 --> 00:13:36.240
These terms can really
be used interchangeably.

00:13:36.240 --> 00:13:38.240
The substrate will
bind to what's

00:13:38.240 --> 00:13:41.530
known as the active
site on an enzyme,

00:13:41.530 --> 00:13:44.670
and so as someone who determines
three dimensional structures

00:13:44.670 --> 00:13:47.860
of enzyme, it pains me to draw
a picture of an enzyme structure

00:13:47.860 --> 00:13:49.690
like this, but I did it anyway.

00:13:49.690 --> 00:13:50.870
So here's my enzyme.

00:13:50.870 --> 00:13:52.230
That's its active site.

00:13:52.230 --> 00:13:54.330
Here is the substrate
molecule, which

00:13:54.330 --> 00:13:56.090
is about the same
size as the enzyme--

00:13:56.090 --> 00:13:58.690
usually that's not the
case, but anyway-- binding.

00:13:58.690 --> 00:14:02.130
And so then when you have enzyme
plus substrate bind together,

00:14:02.130 --> 00:14:06.400
we have our ES complex,
ES for enzyme substrate.

00:14:06.400 --> 00:14:11.746
And then the enzyme will undo
catalysis, forming product.

00:14:11.746 --> 00:14:13.370
And product will be
released, and we'll

00:14:13.370 --> 00:14:15.790
have free enzyme again.

00:14:15.790 --> 00:14:19.610
So this is a very
simple mechanism

00:14:19.610 --> 00:14:25.220
or steps of enzyme
catalysis, but that's OK.

00:14:25.220 --> 00:14:28.510
It sometimes can be written
in a very simple way.

00:14:28.510 --> 00:14:32.030
And so now, using
what you have already

00:14:32.030 --> 00:14:35.320
learned how to do in
our reaction mechanism,

00:14:35.320 --> 00:14:40.300
we can derive rate laws and
rate expressions for enzymes.

00:14:40.300 --> 00:14:42.630
So you know biochemistry
is really not

00:14:42.630 --> 00:14:45.070
much different than anything
else we've been doing.

00:14:45.070 --> 00:14:47.150
All the things you've
been learning in chemistry

00:14:47.150 --> 00:14:48.710
apply to biochemistry.

00:14:48.710 --> 00:14:51.570
Biochemistry or life
is really just a series

00:14:51.570 --> 00:14:53.960
of chemical reactions
that obey all

00:14:53.960 --> 00:14:57.840
of the same laws and
principles as everything else.

00:14:57.840 --> 00:15:02.230
So here we're going to write
an expression for the enzyme

00:15:02.230 --> 00:15:04.070
coming together
with its substrate,

00:15:04.070 --> 00:15:07.390
forming an intermediate
enzyme substrate complex,

00:15:07.390 --> 00:15:11.020
and going on to form
free enzyme and product.

00:15:11.020 --> 00:15:15.320
In step one, enzyme and
substrate will come together.

00:15:15.320 --> 00:15:17.070
And in the forward
direction, we have

00:15:17.070 --> 00:15:20.890
k1 to form the enzyme
complex, and it's also

00:15:20.890 --> 00:15:22.390
a reversible step.

00:15:22.390 --> 00:15:26.750
In step two, the complex goes
on to form enzyme and product.

00:15:26.750 --> 00:15:28.930
So we can now write
these laws, or I

00:15:28.930 --> 00:15:33.380
should say you can figure out
how to write these expressions.

00:15:33.380 --> 00:15:37.118
These are, again, elementary
steps, elementary reactions.

00:15:53.350 --> 00:15:54.355
10 more seconds.

00:16:12.150 --> 00:16:16.430
OK let's just take
a look at that.

00:16:16.430 --> 00:16:20.090
So over here, again the rate
of the forward direction,

00:16:20.090 --> 00:16:24.820
we have the forward rate
constant K1 times enzyme times

00:16:24.820 --> 00:16:26.510
substrate.

00:16:26.510 --> 00:16:29.150
And for the reverse
direction, it's

00:16:29.150 --> 00:16:34.480
k minus 1 times our
intermediate ES.

00:16:34.480 --> 00:16:38.360
So now that you remember
how those are done,

00:16:38.360 --> 00:16:41.240
you can tell me-- you can
just yell it out-- what

00:16:41.240 --> 00:16:42.670
am I going to put for this rate?

00:16:47.380 --> 00:16:48.870
K2 times ES.

00:16:51.760 --> 00:16:52.260
All right.

00:16:52.260 --> 00:16:56.340
So we can always, from
an elementary step

00:16:56.340 --> 00:16:59.270
or elementary reaction,
write the rate law just

00:16:59.270 --> 00:17:02.350
based on the stoichiometry,
using our rate constants

00:17:02.350 --> 00:17:05.960
and our reactants here.

00:17:05.960 --> 00:17:08.900
Or for the reverse
direction here.

00:17:08.900 --> 00:17:13.140
And then we can write the
overall rate at which product

00:17:13.140 --> 00:17:14.530
is being formed.

00:17:14.530 --> 00:17:16.230
So the rate of
product formation,

00:17:16.230 --> 00:17:19.470
we can write it from the slow
step or from our last step

00:17:19.470 --> 00:17:22.460
if we don't know anything
about slow steps.

00:17:22.460 --> 00:17:24.390
So the rate at which
product is formed

00:17:24.390 --> 00:17:30.530
can be expressed as DPDT, the
change in product over time.

00:17:30.530 --> 00:17:34.690
And you can also write it by the
rate law for this second step,

00:17:34.690 --> 00:17:37.260
K2 times ES.

00:17:37.260 --> 00:17:40.060
But we're not done, because
ES is an intermediate.

00:17:40.060 --> 00:17:43.070
It's formed in the
first step, and consumed

00:17:43.070 --> 00:17:44.450
in the second step.

00:17:44.450 --> 00:17:46.630
And so it's an
intermediate, so we now

00:17:46.630 --> 00:17:51.260
have to solve for ES in terms
of rate constants, products,

00:17:51.260 --> 00:17:53.600
and reactants.

00:17:53.600 --> 00:17:56.090
So how are we going to do this?

00:17:56.090 --> 00:17:59.360
And why don't you tell
me how we do this?

00:17:59.360 --> 00:18:03.720
And again, this is the
change in ES over time.

00:18:03.720 --> 00:18:07.720
So asking for the rate of change
of the intermediate over time.

00:18:18.710 --> 00:18:19.963
All right 10 more seconds.

00:18:34.444 --> 00:18:34.944
OK.

00:18:34.944 --> 00:18:36.430
Yep.

00:18:36.430 --> 00:18:41.340
So if you remember back
to the mechanism lecture,

00:18:41.340 --> 00:18:46.410
you can solve for ES by
looking at the rate at which ES

00:18:46.410 --> 00:18:49.700
is formed, the rate at
which it's decomposed,

00:18:49.700 --> 00:18:52.590
and the rate at
which it's consumed.

00:18:52.590 --> 00:18:56.170
So the rate of formation
is the forward direction

00:18:56.170 --> 00:19:00.800
of the first step minus the
rate at which it decomposes,

00:19:00.800 --> 00:19:03.760
which is the back direction
of the first step.

00:19:03.760 --> 00:19:07.830
So we have plus K1 E times
S minus k minus 1 times

00:19:07.830 --> 00:19:12.360
the intermediate concentration,
and then minus the consumption

00:19:12.360 --> 00:19:15.710
minus K2 times ES.

00:19:15.710 --> 00:19:18.420
So we put all those
steps together,

00:19:18.420 --> 00:19:22.780
and then we need to use the
steady state approximation

00:19:22.780 --> 00:19:27.640
to take this to solve for ES.

00:19:27.640 --> 00:19:30.820
So again, the steady
state approximation

00:19:30.820 --> 00:19:35.430
says that the rate at which
an intermediate forms equals

00:19:35.430 --> 00:19:37.850
the rate at which the
intermediate goes away

00:19:37.850 --> 00:19:41.700
or the net rate is 0.

00:19:41.700 --> 00:19:45.950
So that is again the
steady state approximation,

00:19:45.950 --> 00:19:48.950
and they use that in enzyme
kinetics as well as pretty much

00:19:48.950 --> 00:19:53.280
every problem you have in
reaction mechanisms-- that's

00:19:53.280 --> 00:19:55.110
going to be on the final.

00:19:55.110 --> 00:19:59.200
All right so using that
steady state approximation,

00:19:59.200 --> 00:20:02.070
we can just take this
expression that we just talked

00:20:02.070 --> 00:20:05.440
about and set it
equal to 0, and that

00:20:05.440 --> 00:20:09.470
will allow for us to solve
for our intermediate, which

00:20:09.470 --> 00:20:12.290
is in this case ES.

00:20:12.290 --> 00:20:15.421
So we set that
whole thing into 0.

00:20:15.421 --> 00:20:15.920
All right.

00:20:15.920 --> 00:20:18.760
So this so far is
exactly the same

00:20:18.760 --> 00:20:22.230
as you would do any problem
in reaction mechanisms.

00:20:22.230 --> 00:20:26.670
But now, because it's enzymes,
there is a slight difference.

00:20:26.670 --> 00:20:29.640
So a slight difference.

00:20:29.640 --> 00:20:33.820
And that is that instead
of solving for ES in terms

00:20:33.820 --> 00:20:37.030
of E or free enzyme,
we want to solve

00:20:37.030 --> 00:20:42.310
for ES in terms of the total
concentration of enzyme, e

00:20:42.310 --> 00:20:45.030
to the 0 or O over here.

00:20:45.030 --> 00:20:49.230
So total enzyme equals free
enzyme plus bound enzyme

00:20:49.230 --> 00:20:51.250
because your enzyme is
either free or bound.

00:20:51.250 --> 00:20:55.320
It only has two options, and
so that's your total enzyme.

00:20:55.320 --> 00:21:00.010
And the reason why we want
to do this is practical.

00:21:00.010 --> 00:21:02.350
We don't necessarily
know if we're

00:21:02.350 --> 00:21:06.000
studying its reaction how
much of our enzyme is free

00:21:06.000 --> 00:21:07.490
and how much is bound.

00:21:07.490 --> 00:21:09.550
But if we're good
scientists, we know

00:21:09.550 --> 00:21:13.650
how much enzyme we put
into our experiment.

00:21:13.650 --> 00:21:16.150
So total enzyme, if we
can solve for things

00:21:16.150 --> 00:21:18.190
and do things in
terms of total enzyme,

00:21:18.190 --> 00:21:20.490
that makes our life much easier.

00:21:20.490 --> 00:21:22.740
So it's a very practical reason.

00:21:22.740 --> 00:21:25.380
So what we can do
now is replace E,

00:21:25.380 --> 00:21:28.520
which is our free enzyme,
with our total enzyme

00:21:28.520 --> 00:21:31.290
minus our bound enzyme.

00:21:31.290 --> 00:21:32.810
So that's what
we're going to do.

00:21:32.810 --> 00:21:35.580
I'm going to put back those
expressions we just had.

00:21:35.580 --> 00:21:37.870
So this was the
clicker question,

00:21:37.870 --> 00:21:40.000
then we set it equal to zero.

00:21:40.000 --> 00:21:42.570
And now we have
this E term here.

00:21:42.570 --> 00:21:44.500
We want to get rid
of that because we

00:21:44.500 --> 00:21:46.330
don't know how much
of our enzyme is free,

00:21:46.330 --> 00:21:49.060
but we do know how much
we put in our total.

00:21:49.060 --> 00:21:53.380
So we're going to place this E
with total enzyme minus bound

00:21:53.380 --> 00:21:54.270
enzyme.

00:21:54.270 --> 00:21:59.230
So we have a k1, now instead
of times E we have times E0

00:21:59.230 --> 00:22:01.820
times our substrate.

00:22:01.820 --> 00:22:06.780
And then we have this ES term,
so minus k1 again, ES times

00:22:06.780 --> 00:22:07.820
substrate.

00:22:07.820 --> 00:22:09.630
And then you had
these two terms.

00:22:09.630 --> 00:22:11.620
We just put those down here.

00:22:11.620 --> 00:22:14.430
OK so now we're back.

00:22:14.430 --> 00:22:18.610
Now we want to solve
for the intermediate ES,

00:22:18.610 --> 00:22:20.650
and we'll solve for
that intermediate ES

00:22:20.650 --> 00:22:24.370
in terms now of total enzyme.

00:22:24.370 --> 00:22:24.870
All right.

00:22:24.870 --> 00:22:27.040
So now we need to do
some rearrangement,

00:22:27.040 --> 00:22:30.370
just putting that expression
up here that we just saw.

00:22:30.370 --> 00:22:33.300
And now we're going to
rearrange our ES terms.

00:22:33.300 --> 00:22:36.180
Everything with an ES to
one side of the equation,

00:22:36.180 --> 00:22:38.510
and then solve for it.

00:22:38.510 --> 00:22:41.475
So we have all of our
ES terms on one side,

00:22:41.475 --> 00:22:45.750
you remove that one, you move
this one, we move that one.

00:22:45.750 --> 00:22:47.510
And on the other
side, we just have

00:22:47.510 --> 00:22:50.930
this term with k1, total
enzyme and substrate.

00:22:50.930 --> 00:22:55.290
Now we can pull out the
ES terms, so ES is here.

00:22:55.290 --> 00:22:58.240
We have k1 times
substrate, k minus 1,

00:22:58.240 --> 00:23:00.500
k2, and then this
term over here,

00:23:00.500 --> 00:23:03.040
k1 total enzyme substrate.

00:23:03.040 --> 00:23:06.570
Now we divide, and we
get this term over here.

00:23:06.570 --> 00:23:10.190
So now we've solved for ES.

00:23:10.190 --> 00:23:10.995
One more change.

00:23:13.760 --> 00:23:16.790
There is a constant that's
easy to measure called

00:23:16.790 --> 00:23:18.960
the Michaelis-Menten Constant.

00:23:18.960 --> 00:23:25.140
And we want to now
introduce this term, big Km,

00:23:25.140 --> 00:23:32.340
and this term is equal sub
k minus 1 plus k2 over k1.

00:23:32.340 --> 00:23:36.820
Now we want to get this new
constant, Michaelis-Menten

00:23:36.820 --> 00:23:40.500
Constant, into this expression
because it's easy to measure.

00:23:40.500 --> 00:23:42.550
Again, practical.

00:23:42.550 --> 00:23:45.090
So let's do that.

00:23:45.090 --> 00:23:48.150
So here's this Km
term again, and we

00:23:48.150 --> 00:23:53.610
want this Km term to
appear in this solution

00:23:53.610 --> 00:23:55.990
to our intermediate.

00:23:55.990 --> 00:23:59.900
We have k minus 1
here, k2, like that,

00:23:59.900 --> 00:24:01.670
but there is no
k1 underneath it.

00:24:01.670 --> 00:24:03.680
So let's put one there.

00:24:03.680 --> 00:24:08.410
So what we're going to do is
we're going to divide by k1.

00:24:08.410 --> 00:24:11.290
So we'll divide
the top term by k1.

00:24:11.290 --> 00:24:15.680
We'll divide and divide
this k1 S term by k1

00:24:15.680 --> 00:24:19.020
and we'll divide k
minus 1 plus k2 by k1,

00:24:19.020 --> 00:24:24.351
and we do that because then
we can get our big Km in here.

00:24:24.351 --> 00:24:24.850
All right.

00:24:24.850 --> 00:24:27.660
So with all of these
dividing by k1s,

00:24:27.660 --> 00:24:31.110
we can simplify this expression.

00:24:31.110 --> 00:24:32.710
And so we'll do that.

00:24:32.710 --> 00:24:35.360
So we'll cancel those k1s.

00:24:35.360 --> 00:24:39.100
We can cancel these k1s.

00:24:39.100 --> 00:24:41.920
And then we can get this.

00:24:41.920 --> 00:24:46.650
Our total enzyme concentration
times substrate over

00:24:46.650 --> 00:24:51.110
substrate concentration plus
Km, because that term equals Km.

00:24:51.110 --> 00:24:54.820
And now we're happy because
we can measure a Km,

00:24:54.820 --> 00:24:57.610
and we know how much
total enzyme we put in.

00:24:57.610 --> 00:24:59.670
So we just solved
for our intermediate

00:24:59.670 --> 00:25:03.659
in terms of things we
can actually measure.

00:25:03.659 --> 00:25:04.450
But we're not done.

00:25:04.450 --> 00:25:07.090
This is just the expression
for intermediate.

00:25:07.090 --> 00:25:10.280
Now we have to put it
back into our rate law.

00:25:10.280 --> 00:25:12.450
So let's do that.

00:25:12.450 --> 00:25:13.960
Almost done.

00:25:13.960 --> 00:25:17.530
Here is our expression
for our intermediate.

00:25:17.530 --> 00:25:19.580
The rate of product
formation, the change

00:25:19.580 --> 00:25:23.810
in product over time, equals
K2 times ES, this intermediate.

00:25:23.810 --> 00:25:29.420
Now we can plug that in
to that term and do that.

00:25:29.420 --> 00:25:31.380
And we get this
expression, which

00:25:31.380 --> 00:25:33.880
is known as the
Michaelis-Menten Equation,

00:25:33.880 --> 00:25:36.770
k2 times total enzyme
times substrate over

00:25:36.770 --> 00:25:40.440
substrate times-- plus Km.

00:25:40.440 --> 00:25:45.030
And let me just show you
some pictures of Maude Menten

00:25:45.030 --> 00:25:46.520
and Michaelis.

00:25:46.520 --> 00:25:52.550
So Michaelis was a professor
in Germany, and he was Jewish.

00:25:52.550 --> 00:25:55.610
And he had a bit
of a rocky career,

00:25:55.610 --> 00:25:58.230
and was encouraged to do things
that, perhaps, no one cared

00:25:58.230 --> 00:26:01.920
about that much, like
study enzymes or something.

00:26:01.920 --> 00:26:06.250
And he worked with Maude
Menten, who was Canadian.

00:26:06.250 --> 00:26:11.720
So Maude Menten couldn't find
a faculty position in Canada

00:26:11.720 --> 00:26:14.710
at the time, so she got
a position in the US

00:26:14.710 --> 00:26:17.010
at University of Pittsburgh.

00:26:17.010 --> 00:26:20.310
Michaelis decided Germany
was not a good place to be,

00:26:20.310 --> 00:26:25.000
and ended up in New York City
at Rockefeller University.

00:26:25.000 --> 00:26:28.250
Maude Menten, although she
published an enormous number

00:26:28.250 --> 00:26:31.370
of papers, and really
Michaelis-Menten Kinetics

00:26:31.370 --> 00:26:32.790
is one of the most
famous things--

00:26:32.790 --> 00:26:34.750
if you ask a
biochemist one thing

00:26:34.750 --> 00:26:38.350
that everyone will know about
it's Michaelis-Menten kinetics.

00:26:38.350 --> 00:26:40.520
She was not promoted
to full professor

00:26:40.520 --> 00:26:43.530
until she was 70 years old,
despite the fact that she

00:26:43.530 --> 00:26:46.760
had accomplished more
than most anybody else.

00:26:46.760 --> 00:26:49.640
And then she retired
at 71 years of age.

00:26:49.640 --> 00:26:53.470
So she was a full professor for
one year before she retired.

00:26:53.470 --> 00:26:55.830
But Michaelis has had
a rough time, too,

00:26:55.830 --> 00:26:59.860
and didn't get his
position that was

00:26:59.860 --> 00:27:03.330
worthy of his accomplishments
until he was in his 50s

00:27:03.330 --> 00:27:05.370
because of being a German Jew.

00:27:05.370 --> 00:27:08.270
So both of them had a
pretty rocky career,

00:27:08.270 --> 00:27:11.380
but they were two of the
most prominent figures

00:27:11.380 --> 00:27:13.890
really in
biochemistry, setting--

00:27:13.890 --> 00:27:16.460
we still use Michaelis-Menten
kinetics all the time

00:27:16.460 --> 00:27:17.440
in biochemistry.

00:27:17.440 --> 00:27:19.670
So this is really
pioneering work.

00:27:19.670 --> 00:27:23.280
OK so let me now
show you how to apply

00:27:23.280 --> 00:27:28.560
the Michaelis-Menten equation
to different conditions.

00:27:28.560 --> 00:27:33.030
So here we have a plot,
a change in product,

00:27:33.030 --> 00:27:34.870
so the rate at which
product is being

00:27:34.870 --> 00:27:39.090
formed vs. our
substrate concentration.

00:27:39.090 --> 00:27:43.680
So as we-- at low substrate
concentrations down here,

00:27:43.680 --> 00:27:47.730
there's a very fast change
in the amount of product

00:27:47.730 --> 00:27:50.320
that's being produced per time.

00:27:50.320 --> 00:27:53.710
So at low substrate
concentration,

00:27:53.710 --> 00:27:57.470
when you add more substrate
it increases the rate

00:27:57.470 --> 00:27:58.880
significantly.

00:27:58.880 --> 00:28:01.060
And this is because there's
a lot of free enzyme.

00:28:01.060 --> 00:28:04.120
So there's enzyme waiting
around to catalyze a reaction.

00:28:04.120 --> 00:28:07.450
You give it more substrate,
you get more product quickly.

00:28:07.450 --> 00:28:12.880
But this levels off up
here, and at high substrate

00:28:12.880 --> 00:28:15.760
concentration,
adding more substrate

00:28:15.760 --> 00:28:17.450
doesn't really
help the rate any.

00:28:17.450 --> 00:28:20.130
It's leveling off, and that's
because all the active sites

00:28:20.130 --> 00:28:23.440
are already filled, so
adding more substrate

00:28:23.440 --> 00:28:24.830
doesn't make it any faster.

00:28:24.830 --> 00:28:26.620
You need to form
product to release it

00:28:26.620 --> 00:28:28.250
for substrate to bind.

00:28:28.250 --> 00:28:32.450
And so all the active site are
filled, the rate levels off.

00:28:32.450 --> 00:28:35.010
So this is the behavior
that you observe

00:28:35.010 --> 00:28:39.620
when typical Michaelis-Menten
kinetics are in play.

00:28:39.620 --> 00:28:42.220
So now let's think about
those two conditions again,

00:28:42.220 --> 00:28:45.340
or two conditions, one at
high substrate concentration

00:28:45.340 --> 00:28:49.370
and one in this range here.

00:28:49.370 --> 00:28:53.870
So going back to our equation,
when substrate concentration is

00:28:53.870 --> 00:28:56.450
much greater than
Km-- and I'm going

00:28:56.450 --> 00:29:01.720
to define Km for you other than
the rate constant in a minute.

00:29:01.720 --> 00:29:03.520
So when that is
true, we can look

00:29:03.520 --> 00:29:05.520
at the Michaelis-Menten
equation and just

00:29:05.520 --> 00:29:09.310
think about what happens if this
substrate concentration is way,

00:29:09.310 --> 00:29:11.710
way bigger than Km.

00:29:11.710 --> 00:29:15.160
So Km, then is much, much
smaller than substrate,

00:29:15.160 --> 00:29:16.860
and it kind of doesn't matter.

00:29:16.860 --> 00:29:20.210
So it's very small
and we can ignore it.

00:29:20.210 --> 00:29:24.290
And if we cancel out Km, then
we can simplify this equation

00:29:24.290 --> 00:29:27.680
even further, and cancel
out our substrates

00:29:27.680 --> 00:29:30.600
and we're left with this, that
the rate of product formation

00:29:30.600 --> 00:29:34.690
is just k2 times
our total enzyme.

00:29:34.690 --> 00:29:36.400
And this has a special name.

00:29:36.400 --> 00:29:41.620
This is called Vmax, the
maximum velocity of the enzyme.

00:29:41.620 --> 00:29:45.660
So maximum velocity
or maximum rate

00:29:45.660 --> 00:29:49.800
equals k2 times your total
enzyme concentration.

00:29:49.800 --> 00:29:52.480
So this is one equation that
you'll find on your equation

00:29:52.480 --> 00:29:55.010
sheet for the final exam.

00:29:55.010 --> 00:29:58.530
And if we go back for a second
and look at our plot up here,

00:29:58.530 --> 00:30:03.130
we can now write Vmax,
the maximum velocity

00:30:03.130 --> 00:30:06.570
for that particular
enzyme concentration,

00:30:06.570 --> 00:30:08.820
k2 times total enzyme.

00:30:08.820 --> 00:30:12.710
This is the maximum
rate we're going to get.

00:30:12.710 --> 00:30:15.830
So now let's think about this
down here at low substrate

00:30:15.830 --> 00:30:20.210
concentrations again, and
particularly at a concentration

00:30:20.210 --> 00:30:24.810
where substrate equals Km,
substrate concentration equals

00:30:24.810 --> 00:30:25.850
Km.

00:30:25.850 --> 00:30:30.780
So if substrate concentration
and Km are the same thing,

00:30:30.780 --> 00:30:34.415
we can just put an extra
substrate in there,

00:30:34.415 --> 00:30:36.350
Km equals substrate.

00:30:36.350 --> 00:30:41.860
So on the bottom we have two
substrate concentrations now,

00:30:41.860 --> 00:30:45.200
and that allows us to
cancel out our substrates.

00:30:45.200 --> 00:30:50.000
And we're left with this
equation 1/2 k2 times

00:30:50.000 --> 00:30:52.480
the total concentration
of enzyme,

00:30:52.480 --> 00:30:55.780
which is the half maximal rate.

00:30:55.780 --> 00:30:57.700
That's half of Vmax.

00:30:57.700 --> 00:31:00.440
Vmax was k2 times total enzyme.

00:31:00.440 --> 00:31:07.410
This is half of that, and
this is the definition of Km.

00:31:07.410 --> 00:31:10.880
Km is the concentration
of substrate for which

00:31:10.880 --> 00:31:14.260
the rate is half maximal.

00:31:14.260 --> 00:31:19.110
So if we go back
now to our plot,

00:31:19.110 --> 00:31:23.610
this is the maximum rate at
half of that maximal rate.

00:31:23.610 --> 00:31:27.300
The substrate
concentration equals Km.

00:31:27.300 --> 00:31:31.110
So experimentally,
you can plot your data

00:31:31.110 --> 00:31:34.600
for the formation of
product at various substrate

00:31:34.600 --> 00:31:40.420
concentrations, calculate
Vmax, and figure out

00:31:40.420 --> 00:31:43.480
what was the concentration
of substrate when

00:31:43.480 --> 00:31:48.960
the rate was half that maximal
rate, and you can determine Km.

00:31:48.960 --> 00:31:51.650
That's why you want
Km in your equation,

00:31:51.650 --> 00:31:55.321
because it's something that's
not that hard to measure.

00:31:55.321 --> 00:31:55.820
OK.

00:31:55.820 --> 00:31:59.560
So let's apply this now.

00:31:59.560 --> 00:32:05.100
Let's think about
an enzyme, and we're

00:32:05.100 --> 00:32:08.590
told this is enzyme
carbonic anhydrase.

00:32:08.590 --> 00:32:13.710
It catalyzed CO2 to
bicarbonate, which

00:32:13.710 --> 00:32:17.260
is the buffering system
that happens in your blood,

00:32:17.260 --> 00:32:20.750
the Michaelis-Menten
constant for this enzyme,

00:32:20.750 --> 00:32:25.030
we have Km 8 times 10
to the minus 5 molar,

00:32:25.030 --> 00:32:31.379
and a k2 value of 6 times 5 to
the fifth, I think-- or sixth.

00:32:31.379 --> 00:32:31.920
I don't know.

00:32:31.920 --> 00:32:33.378
I don't have my
glasses, [? for ?].

00:32:33.378 --> 00:32:35.070
Hopefully you can
see better than me.

00:32:35.070 --> 00:32:35.570
All right.

00:32:35.570 --> 00:32:42.100
So now with these values,
calculate the maximal reaction

00:32:42.100 --> 00:32:46.940
rate if the enzyme concentration
is this, which I think

00:32:46.940 --> 00:32:51.940
is 5 times 10 to
the something molar.

00:32:51.940 --> 00:32:53.309
They should make bigger fonts.

00:32:53.309 --> 00:32:54.600
Oh it's easier to read on that.

00:32:54.600 --> 00:32:55.635
OK, clicker question.

00:33:10.530 --> 00:33:11.220
All right.

00:33:11.220 --> 00:33:11.990
10 more seconds.

00:33:25.850 --> 00:33:27.490
Yep.

00:33:27.490 --> 00:33:30.430
So here you just had to say OK.

00:33:30.430 --> 00:33:33.020
If you had your glasses--
and I have my now.

00:33:33.020 --> 00:33:36.240
Enzyme concentration
times k2 is going

00:33:36.240 --> 00:33:39.780
to give you the maximum rate,
so Vmax equals K2 times enzyme

00:33:39.780 --> 00:33:41.461
concentration.

00:33:41.461 --> 00:33:41.960
All right.

00:33:41.960 --> 00:33:46.510
So we can put that down Vmax
k2 enzyme concentration.

00:33:46.510 --> 00:33:50.990
Multiply those out together,
and you get the rate,

00:33:50.990 --> 00:33:53.670
and it's in molar per second.

00:33:53.670 --> 00:34:00.150
Now what about the concentration
of substrate for the rate

00:34:00.150 --> 00:34:03.979
to be 1.5 molar per second?

00:34:03.979 --> 00:34:05.020
Another clicker question.

00:34:21.320 --> 00:34:21.820
All right.

00:34:21.820 --> 00:34:22.499
10 more seconds.

00:34:37.960 --> 00:34:39.489
Wow.

00:34:39.489 --> 00:34:41.100
OK.

00:34:41.100 --> 00:34:52.730
So what is this number compared
to the number we had a before?

00:34:52.730 --> 00:34:55.210
It's the half maximal rate.

00:34:55.210 --> 00:34:59.690
So what is the enzyme--
the substrate concentration

00:34:59.690 --> 00:35:02.620
at the half maximal rate?

00:35:02.620 --> 00:35:03.680
Km.

00:35:03.680 --> 00:35:04.460
Yeah.

00:35:04.460 --> 00:35:08.060
So all you had to do--
that's the definition of Km

00:35:08.060 --> 00:35:11.850
is look for the Km
value and say that is

00:35:11.850 --> 00:35:15.330
the substrate concentration
when the rate is half maximal.

00:35:15.330 --> 00:35:17.520
And so this is the
kind of problem

00:35:17.520 --> 00:35:21.950
that you'll have that the
extra problems have in them.

00:35:21.950 --> 00:35:23.770
And this can be the
complete answer.

00:35:23.770 --> 00:35:26.060
You don't have to show
any work for these.

00:35:26.060 --> 00:35:27.660
So a lot of these
problems are just

00:35:27.660 --> 00:35:33.270
looking for you to identify
or know what Km means.

00:35:33.270 --> 00:35:37.290
So again, that's all
you have to do for this.

00:35:37.290 --> 00:35:40.460
So check out the extra
problems on kinetics.

00:35:40.460 --> 00:35:42.530
They're not really
extra, they're

00:35:42.530 --> 00:35:45.760
on enzymes and things,
reaction mechanisms that

00:35:45.760 --> 00:35:47.460
haven't been on a problem set.

00:35:47.460 --> 00:35:49.800
They will be on the final exam.

00:35:49.800 --> 00:35:53.130
OK and then we'll talk briefly
about inhibitors, clicker

00:35:53.130 --> 00:35:55.920
competition Wednesday,
and we're going

00:35:55.920 --> 00:35:58.090
to review a lot of
the topics that we've

00:35:58.090 --> 00:35:59.460
covered on Wednesday.

00:35:59.460 --> 00:36:01.000
So it's going to
be a lot of fun.

00:36:01.000 --> 00:36:03.230
And our last video.

00:36:03.230 --> 00:36:03.730
All right.

00:36:03.730 --> 00:36:07.000
So quickly, we've got to get
to our clicker competition.

00:36:07.000 --> 00:36:13.330
So let's finish
lecture 34 notes.

00:36:13.330 --> 00:36:15.830
So the last thing we've
been talking about

00:36:15.830 --> 00:36:18.670
is one of the most exciting
things in chemistry, which

00:36:18.670 --> 00:36:22.560
is catalysis, how do
you speed up reactions?

00:36:22.560 --> 00:36:25.780
But we have to end
on a slow note, which

00:36:25.780 --> 00:36:29.820
is that inhibitors are
the opposite of catalysts,

00:36:29.820 --> 00:36:33.370
and they slow down reactions.

00:36:33.370 --> 00:36:35.380
And if we're talking
about enzymes,

00:36:35.380 --> 00:36:40.440
which we were doing on Monday,
then inhibitors will often

00:36:40.440 --> 00:36:43.970
bind to the enzyme E,
forming an EI complex,

00:36:43.970 --> 00:36:46.080
an enzyme inhibitor complex.

00:36:46.080 --> 00:36:48.480
And they often bind
in the active site,

00:36:48.480 --> 00:36:51.810
and so therefore substrate,
which we have here,

00:36:51.810 --> 00:36:54.200
little substrate S, cannot bind.

00:36:54.200 --> 00:36:55.810
It's a very simple idea.

00:36:55.810 --> 00:36:57.420
If you want to
design an inhibitor

00:36:57.420 --> 00:37:00.600
to stop an enzyme from doing
what it's doing-- and in fact

00:37:00.600 --> 00:37:03.780
the pharmaceutical industry
is largely about this,

00:37:03.780 --> 00:37:07.930
designing inhibitors to bind to
key enzymes to stop processes.

00:37:07.930 --> 00:37:10.279
So often what you do
in designing this,

00:37:10.279 --> 00:37:12.570
you want something that kind
of looks like a substrate.

00:37:12.570 --> 00:37:14.930
But most ideally
you want something

00:37:14.930 --> 00:37:18.830
that actually resembles the
transition state-- a transition

00:37:18.830 --> 00:37:20.030
state analog.

00:37:20.030 --> 00:37:23.520
So you remember catalysts work
by lowering the transition

00:37:23.520 --> 00:37:27.430
state or activation energy
barriers, or activated complex.

00:37:27.430 --> 00:37:29.710
So they lower that energy.

00:37:29.710 --> 00:37:32.690
And so something that resembles
the transition state, where

00:37:32.690 --> 00:37:36.810
bonds are partly broken, partly
formed, it's not reactants,

00:37:36.810 --> 00:37:39.430
it's not products,
it's in the middle.

00:37:39.430 --> 00:37:42.050
Those molecules, those
analogs of transition

00:37:42.050 --> 00:37:45.110
states will bond very tightly
and will block the enzyme

00:37:45.110 --> 00:37:46.101
from doing its job.

00:37:46.101 --> 00:37:47.850
And this is really--
I told you about it--

00:37:47.850 --> 00:37:49.910
we had World AIDS
Day I mentioned

00:37:49.910 --> 00:37:52.590
that one of the
reasons why AIDS is not

00:37:52.590 --> 00:37:55.280
such a huge problem in the
US anymore, it's not a death

00:37:55.280 --> 00:37:59.010
sentence anymore, is because
the pharmaceutical industry

00:37:59.010 --> 00:38:02.925
designed transition state
analogs targeting HIV protease.

00:38:02.925 --> 00:38:04.300
And they really
worked very well.

00:38:04.300 --> 00:38:06.730
So for in the developing
world, there's

00:38:06.730 --> 00:38:10.010
a good regime of
pharmaceuticals that we can take

00:38:10.010 --> 00:38:12.010
that keep the viral load low.

00:38:12.010 --> 00:38:14.910
Now it's different in
other parts of the world,

00:38:14.910 --> 00:38:16.880
but a lot of the
pharmaceutical industry

00:38:16.880 --> 00:38:19.610
is about designing
inhibitors for enzymes.

00:38:19.610 --> 00:38:21.850
OK so we've been
talking about catalysis.

00:38:21.850 --> 00:38:24.807
We talked about catalytic
mechanisms, catalysts,

00:38:24.807 --> 00:38:26.390
we talked about
effect of temperature,

00:38:26.390 --> 00:38:27.620
all sorts of things.

00:38:27.620 --> 00:38:29.990
And so we're going
to end our catalysis

00:38:29.990 --> 00:38:34.650
unit with our final video in
the series In Their Own Words.

00:38:34.650 --> 00:38:36.250
And this is a former
graduate student.

00:38:36.250 --> 00:38:38.260
She actually just
defended I'm talking

00:38:38.260 --> 00:38:40.720
about her work in Tony
Synskey's laboratory,

00:38:40.720 --> 00:38:45.150
and why kinetics are
important to our research

00:38:45.150 --> 00:38:46.924
and development of biofuels.

00:38:46.924 --> 00:38:47.590
[VIDEO PLAYBACK]

00:38:47.590 --> 00:38:48.464
- My name is Jingnan.

00:38:48.464 --> 00:38:51.430
I'm from Chongqing China,
and I'm a third year graduate

00:38:51.430 --> 00:38:55.640
student working in the chemistry
and biology department.

00:38:55.640 --> 00:38:57.840
My research she's on
converting carbon dioxide,

00:38:57.840 --> 00:39:02.690
an environmental pollutant,
into a useful biofuel.

00:39:02.690 --> 00:39:07.140
Right now, currently, we
burn ethanol in our gasoline.

00:39:07.140 --> 00:39:09.130
And ethanol is
not an ideal fuel,

00:39:09.130 --> 00:39:11.010
because it's a
shorter chain link,

00:39:11.010 --> 00:39:12.640
and the combustion
of heat is not

00:39:12.640 --> 00:39:16.000
as high as longer
chain length alcohols.

00:39:16.000 --> 00:39:18.430
Also, ethanol traps
a lot of water,

00:39:18.430 --> 00:39:22.100
so it can cool off the engine.

00:39:22.100 --> 00:39:24.390
When they first found
the Ralstonia eutropha

00:39:24.390 --> 00:39:27.670
they realized that this organism
can store a lot of its carbon

00:39:27.670 --> 00:39:30.930
as a polymer chain of esters.

00:39:30.930 --> 00:39:33.450
And these polyesters,
when isolated,

00:39:33.450 --> 00:39:36.481
can be used as
biodegradable plastics.

00:39:36.481 --> 00:39:40.360
for my research, I'm trying
to turn this carbon storage

00:39:40.360 --> 00:39:44.460
organism into storing the carbon
as biofuels, so an alcohol

00:39:44.460 --> 00:39:47.920
that can burn in our engines.

00:39:47.920 --> 00:39:51.400
To change these organisms from
making biodegradable plastics

00:39:51.400 --> 00:39:53.960
to make biofuels,
first I have to get rid

00:39:53.960 --> 00:39:58.530
of the gene that actually makes
the biodegradable plastics,

00:39:58.530 --> 00:40:01.030
and then fine tune
another pathway

00:40:01.030 --> 00:40:06.660
to shun the excess carbon
into making biofuels.

00:40:06.660 --> 00:40:08.510
I really have to
think about kinetics,

00:40:08.510 --> 00:40:10.440
because I wanted
my pathway to go

00:40:10.440 --> 00:40:13.670
as fast as it can to produce
as much product as possible

00:40:13.670 --> 00:40:15.490
within a period of time.

00:40:15.490 --> 00:40:19.240
So there are certain parameters
for kinetics that I can change,

00:40:19.240 --> 00:40:21.870
and certain parameters
that I cannot change.

00:40:21.870 --> 00:40:23.860
For the parameters
that I cannot change,

00:40:23.860 --> 00:40:26.990
is the temperature because
my organism would not survive

00:40:26.990 --> 00:40:28.960
under higher temperature.

00:40:28.960 --> 00:40:31.370
And for parameters that I
can change, for example,

00:40:31.370 --> 00:40:33.120
I can change that
enzyme by putting

00:40:33.120 --> 00:40:37.190
in a stronger and more efficient
enzyme from another organism

00:40:37.190 --> 00:40:40.200
to catalyze the
same exact reaction.

00:40:40.200 --> 00:40:43.170
I can also increase the
substrate concentration

00:40:43.170 --> 00:40:47.120
by eliminating another competing
pathway for the same substrate

00:40:47.120 --> 00:40:51.120
by deleting the gene, so hence
making more of the substrate

00:40:51.120 --> 00:40:53.700
out going into my product.

00:40:53.700 --> 00:40:56.750
Eventually we'll be able to
take the carbon dioxide that's

00:40:56.750 --> 00:40:59.200
released as a
pollutant, and trap it

00:40:59.200 --> 00:41:02.410
and use it as a carbon source
to make useful molecules.

00:41:02.410 --> 00:41:04.560
[END PLAYBACK]