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PROFESSOR: Today is our final
clicker competition.

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The first question is up.

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00:00:27,390 --> 00:00:30,780
And I would just like to go over
the current standing for

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00:00:30,780 --> 00:00:34,710
the clicker competition as we're
getting started here.

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So, recitation 6 has two wins,
and there are other

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recitations and have one win, so
recitation 2, 3, 5, 7, and

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10 have one win.

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00:00:49,810 --> 00:00:53,740
If any of those recitation wins
today, we're going to go

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00:00:53,740 --> 00:00:59,780
to a tie breaker to decide the
overall recitation champion.

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00:00:59,780 --> 00:01:05,070
There are also recitations 1, 4,
9, and 11, who are looking

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for their first win.

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This is their last
chance today.

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So, if they win today, they can
not be overall champions,

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but they will have snacks,
and they will assure that

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recitations 2, 3, 5, 7, and
10 do not win the overall

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competition.

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So, you have a chance to
foil those recitations.

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And if we need to go to a tie
breaker, it will not be from

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current material, it's going
to be past material or past

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things that were mentioned.

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So, just keep that in mind.

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All right, and for the overall
winner, I just would like to

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00:01:47,560 --> 00:01:52,220
show you what you will win, so
members of the recitation will

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each get their own chemistry
t-shirt, and at some schools,

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of course, you would look at
this and say oh, they're on

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the varsity team, but at MIT,
it means that you are

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associated with course 5.

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So, Department of Chemistry at
Massachusetts Institute of

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Technology on the back, and we
have different colors and

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different sizes.

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All right, so time to get
started with the clicker

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competition.

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Go ahead and click in your
first responses.

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OK, let's just take
10 more seconds.

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All right.

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Big improvement from the first
time we asked this question

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last class where it's about
33%, now we're up to 89.

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And no, it is not temperature
dependent.

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And we're going to be
talking more about

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activation energy today.

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All right, so today we're going
to finish up kinetics,

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00:03:21,960 --> 00:03:24,950
and we're going to start with
the material that we didn't

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quite get to at the
end of last class.

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And I love this part, because
I love it when we can think

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about what we learned before in
a slightly different way.

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00:03:36,240 --> 00:03:39,240
So, when I first started
lecturing, I was talking about

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LeChatelier principle and, of
course, encouraged students to

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00:03:45,040 --> 00:03:48,240
sort of -- you know it's not too
intuitive to MIT students,

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00:03:48,240 --> 00:03:51,890
but LeChatelier's principle says
that if you apply stress

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to a system, it tends to respond
in such a way to

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minimize that stress.

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So it's all about minimizing
stress, which is something

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that's hard to kind to imagine
this time of year, a little

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easier to imagine activation
energy barriers, a little hard

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to imagine minimizing stress.

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00:04:08,950 --> 00:04:12,790
But we're back to talking
about minimizing stress.

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And we talked about adding
reagents and removing

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products, and we talked about
how reactions will shift to

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respond to stresses.

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And one of the things we talked
about is rationalizing

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the shift of reactions at
equilibrium when temperature

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has changed.

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00:04:30,370 --> 00:04:33,480
So, if you increase the
temperature of a particular

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reaction, it tends to shift in
the endothermic direction to

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remove that added heat
from the reaction.

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So, that's what we learned
before, but now we're going to

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think about this in a slightly
different way.

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So we're going to think about
this in terms of these

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reaction coordinate diagrams.
So, on one axis we have p e

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plotted -- what does
that stand for?

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Potential energy, right, so we
have potential energy going up

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on both sides.

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And here we have a view of an
endothermic reaction, and over

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here is an exothermic
reaction.

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So, let's just take
a look at this.

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For the endothermic reaction,
we have reactants and

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products, we have a delta e
between those, and we have a

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very large activation
energy barrier

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for the forward direction.

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And, of course, for anything to
react, there always has to

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be some barrier, you need some
amount of critical energy,

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because as the molecules come
close to each other, and if

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they're going to react and form
some kind of product, you

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00:05:34,950 --> 00:05:38,090
have to sort of distort bonds
and sort of rearrange things,

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00:05:38,090 --> 00:05:40,310
and that takes a certain
amount of energy.

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00:05:40,310 --> 00:05:42,610
So if they come together and
they have that energy, they'll

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00:05:42,610 --> 00:05:45,360
react and go on to products,
if they don't they'll break

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apart and go back and
be reactants.

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And how much temperature the
system has, is more likely

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00:05:52,810 --> 00:05:54,390
that they'll be able to react.

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So it's more likely, if there's
high temperature, they

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could overcome this activation
energy barrier.

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00:06:06,110 --> 00:06:07,760
All right, so in an endothermic
reaction, you have

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a big one in the forward
direction, and a much smaller

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activation energy in the
reverse direction.

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00:06:13,140 --> 00:06:16,420
For exothermic reaction it's
the reverse -- there's a

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00:06:16,420 --> 00:06:19,450
smaller barrier for the forward
direction, and a much

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larger barrier for the
reverse direction.

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00:06:24,240 --> 00:06:27,670
So, we can think about
the sign of delta e.

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So delta e, this difference here
which is related to delta

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h for liquids and solids, it's
pretty much the same for gases

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is 1% or 2% different.

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00:06:39,100 --> 00:06:41,440
So you have a positive value
here, and you can get a

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00:06:41,440 --> 00:06:45,370
positive delta e here if you
have a big number for the

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00:06:45,370 --> 00:06:49,260
forward activation energy
barrier minus a small number

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for the reverse, so that's
going to give

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you a positive number.

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00:06:52,550 --> 00:06:55,230
For an exothermic reaction,
delta e's going to be

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00:06:55,230 --> 00:06:58,360
negative, and you get a negative
number if you take a

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00:06:58,360 --> 00:07:01,840
small number here for the
forward activation energy, and

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00:07:01,840 --> 00:07:05,080
subtract it from a larger number
here for the reverse

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00:07:05,080 --> 00:07:06,530
activation energy.

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00:07:06,530 --> 00:07:09,040
And remember, this is one of the
equations that we're not

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going to give you, you need to
have that memorized because

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00:07:11,820 --> 00:07:14,490
it's part of understanding
what's going on in these

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00:07:14,490 --> 00:07:16,160
diagrams.

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So now let's think about what
increasing the temperature is

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going to do.

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So, it will help the molecules
if the is temperatures

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increase, they'll have enough
energy to overcome barriers.

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Now if the barriers are pretty
small, then it's not very hard

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00:07:30,850 --> 00:07:33,430
for the molecules to get over
them, regardless of the

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00:07:33,430 --> 00:07:34,450
temperature.

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But when the barrier is big,
then temperature is going to

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00:07:37,910 --> 00:07:39,390
make a big difference.

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00:07:39,390 --> 00:07:42,030
And you can sort of think about
this in your own life as

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00:07:42,030 --> 00:07:45,170
you have a small assignment to
do, you just jump in and do it

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and get it done and it's fine.

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00:07:46,380 --> 00:07:49,860
But if it's a very, very large
thing that you have to do, you

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00:07:49,860 --> 00:07:51,960
often need to procrastinate
longer before

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00:07:51,960 --> 00:07:53,190
you start doing it.

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00:07:53,190 --> 00:07:56,840
So, a small barrier's not so
much of a problem, but if it's

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00:07:56,840 --> 00:08:00,020
a big barrier, you need to
increase that temperature to

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00:08:00,020 --> 00:08:03,800
help the molecules get over
the bigger barriers.

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00:08:03,800 --> 00:08:06,450
So, let's think about what this
means in terms of the

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00:08:06,450 --> 00:08:09,040
direction that a reaction
might shift.

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00:08:09,040 --> 00:08:11,870
So, if you increase a
temperature over here with an

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00:08:11,870 --> 00:08:15,410
endothermic reaction, it makes
it easier to overcome the

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00:08:15,410 --> 00:08:16,550
bigger barrier.

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00:08:16,550 --> 00:08:19,550
The forward reaction barrier
is the bigger one, so

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00:08:19,550 --> 00:08:22,310
increasing the temperature will
help molecules get over

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00:08:22,310 --> 00:08:22,800
that barrier.

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00:08:22,800 --> 00:08:25,470
They're already doing fine with
the reverse barrier, it's

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00:08:25,470 --> 00:08:27,740
the forward barrier that we're
having trouble with.

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00:08:27,740 --> 00:08:30,330
So, if you increase the
temperature, that's going to

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shift the equilibrium toward
products, or it will shift the

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00:08:34,030 --> 00:08:36,500
reaction in the endothermic
direction.

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00:08:36,500 --> 00:08:38,900
That's what we had learned
before with LeChatelier's

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00:08:38,900 --> 00:08:41,650
principle, but now there's a new
way of thinking about why

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00:08:41,650 --> 00:08:43,190
that is true.

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00:08:43,190 --> 00:08:46,650
So, for an exothermic reaction,
if you increase the

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00:08:46,650 --> 00:08:48,800
temperature, that helps with
the bigger barrier.

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00:08:48,800 --> 00:08:52,970
Again, here the bigger barrier
is for the reverse reaction.

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00:08:52,970 --> 00:08:56,170
So, if you increase the
temperature of an exothermic

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00:08:56,170 --> 00:08:59,770
reaction, it's going to shift
it toward reactants.

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00:08:59,770 --> 00:09:03,710
More molecules can overcome that
reverse barrier, and so

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00:09:03,710 --> 00:09:08,260
you'll form more reactants,
it'll shift toward reactants

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00:09:08,260 --> 00:09:11,260
or it'll shift in the
endothermic direction.

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00:09:11,260 --> 00:09:14,030
Again, these are the same things
that we already knew

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00:09:14,030 --> 00:09:16,560
from LeChatelier, but it's a
different way of thinking

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00:09:16,560 --> 00:09:20,960
about why those things
are true.

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00:09:20,960 --> 00:09:25,650
So, a large activation energy
barrier means that rate

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00:09:25,650 --> 00:09:29,760
constants are very sensitive
to temperature.

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00:09:29,760 --> 00:09:33,990
And so, if you have a big
activation energy barrier,

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00:09:33,990 --> 00:09:36,950
increasing the temperature makes
a big difference -- if

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00:09:36,950 --> 00:09:39,620
it's a big barrier, then there's
going to have a big

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00:09:39,620 --> 00:09:42,130
difference if you have
higher temperature.

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00:09:42,130 --> 00:09:45,330
If it's a small barrier, then
increasing the temperature

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00:09:45,330 --> 00:09:47,690
doesn't make much
of a difference.

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00:09:47,690 --> 00:09:49,740
And so you can think about
that in terms of these

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00:09:49,740 --> 00:09:53,550
diagrams as well.

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00:09:53,550 --> 00:09:56,440
So, now we're done with
temperature and we're going to

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00:09:56,440 --> 00:10:00,530
talk about catalysis and
the use of catalysts.

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00:10:00,530 --> 00:10:03,060
And so, if you remember there
were factors affecting the

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00:10:03,060 --> 00:10:07,530
reaction, and we've talked about
everything on this list

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00:10:07,530 --> 00:10:08,890
except for catalysts.

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00:10:08,890 --> 00:10:13,170
So today we're going to
talk about catalysts.

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00:10:13,170 --> 00:10:17,010
So, a catalyst is a substance
that speeds up a reaction, but

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00:10:17,010 --> 00:10:20,600
it doesn't get consumed in the
reaction, it doesn't undergo

187
00:10:20,600 --> 00:10:22,410
any permanent change itself.

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00:10:22,410 --> 00:10:25,540
It's just added to speed
up the reaction.

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00:10:25,540 --> 00:10:31,820
So catalysts do not appear in
the overall balanced equation.

190
00:10:31,820 --> 00:10:34,200
So let's look at what a catalyst
is going to do, and

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00:10:34,200 --> 00:10:36,100
we're going to look at in
terms of these potential

192
00:10:36,100 --> 00:10:38,270
energy diagrams as well.

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00:10:38,270 --> 00:10:41,600
So here we here we have a
reaction, we're going from

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reactants down here
to products.

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00:10:43,990 --> 00:10:46,900
We have the delta e for the
reaction, we have a forward

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00:10:46,900 --> 00:10:49,910
activation energy barrier
and a reverse one.

197
00:10:49,910 --> 00:10:53,550
So, up here, at the top, that's
our barrier without a

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00:10:53,550 --> 00:10:56,410
catalyst. This is the transition
state or the

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00:10:56,410 --> 00:10:59,980
activated complex up here, so
you have to overcome the

200
00:10:59,980 --> 00:11:03,930
barrier, you form some kind of
activated complex, which then,

201
00:11:03,930 --> 00:11:06,940
if there's enough energy to
overcome that barrier, goes on

202
00:11:06,940 --> 00:11:08,680
to products.

203
00:11:08,680 --> 00:11:11,430
So when you add a catalyst
what happens is

204
00:11:11,430 --> 00:11:14,090
it lowers this barrier.

205
00:11:14,090 --> 00:11:17,750
So, in the blue line
here is the new

206
00:11:17,750 --> 00:11:19,770
activation energy barrier.

207
00:11:19,770 --> 00:11:22,900
This is the barrier with a
catalyst, and so this would

208
00:11:22,900 --> 00:11:27,380
then be the new transition
state with a catalyst.

209
00:11:27,380 --> 00:11:30,040
So when it lowers the barrier,
it's going to lower the

210
00:11:30,040 --> 00:11:32,670
barrier for the forward
reaction, so we have a new

211
00:11:32,670 --> 00:11:36,110
activation energy for the
forward reaction, and we're

212
00:11:36,110 --> 00:11:38,320
going to have a new
activation energy

213
00:11:38,320 --> 00:11:41,260
for the reverse direction.

214
00:11:41,260 --> 00:11:45,470
So catalysts work by reducing
both the forward and the

215
00:11:45,470 --> 00:11:48,800
reverse activation
energy barrier.

216
00:11:48,800 --> 00:11:51,610
And another way that you can
say this is that they

217
00:11:51,610 --> 00:11:54,070
stabilize the activated
complex or

218
00:11:54,070 --> 00:11:55,490
the transition state.

219
00:11:55,490 --> 00:11:59,060
So here you have an activated
complex with a much higher

220
00:11:59,060 --> 00:12:03,240
potential energy without the
catalysts, and by stabilizing,

221
00:12:03,240 --> 00:12:06,670
you lower in energy that
transition state.

222
00:12:06,670 --> 00:12:09,040
So that's another way
of expressing

223
00:12:09,040 --> 00:12:13,580
what a catalyst does.

224
00:12:13,580 --> 00:12:17,500
So, catalysts have no effect on
the thermodynamics of the

225
00:12:17,500 --> 00:12:20,960
reaction, they affect the
kinetics of the reaction, but

226
00:12:20,960 --> 00:12:22,210
they don't affect the

227
00:12:22,210 --> 00:12:25,680
thermodynamics of the reaction.

228
00:12:25,680 --> 00:12:28,330
And so, of course, when you
think of thermodynamics, you

229
00:12:28,330 --> 00:12:30,830
often think of delta g.

230
00:12:30,830 --> 00:12:37,890
So, why don't you tell me what
you think, what would happen

231
00:12:37,890 --> 00:12:40,610
about, so delta g is a state
function, it's independent of

232
00:12:40,610 --> 00:12:44,080
path, and so therefore, what
can you tell me about the

233
00:12:44,080 --> 00:12:48,020
equilibrium constant in the
presence of a catalyst?

234
00:12:48,020 --> 00:13:44,630
OK, let's just take
10 more seconds.

235
00:13:44,630 --> 00:13:49,560
Yup, very good.

236
00:13:49,560 --> 00:13:52,920
So, the equilibrium constant
is not changed.

237
00:13:52,920 --> 00:13:56,300
The thermodynamics, which
includes delta g and the

238
00:13:56,300 --> 00:14:01,390
equilibrium constant are not
affected, the rates of the

239
00:14:01,390 --> 00:14:06,980
reaction are affected.

240
00:14:06,980 --> 00:14:10,590
All right, so opposite of a
catalyst is an inhabitor, and

241
00:14:10,590 --> 00:14:14,410
we'll talk more about this at
the end of class, so it would

242
00:14:14,410 --> 00:14:18,930
-- inhibitor is slow or
sometimes stop the rate of the

243
00:14:18,930 --> 00:14:23,360
reaction, and one way that they
do this is by increasing

244
00:14:23,360 --> 00:14:27,250
the activation energy.

245
00:14:27,250 --> 00:14:30,820
So let's consider types
of catalysts now.

246
00:14:30,820 --> 00:14:34,260
You can have a homogeneous
catalyst, which is in the same

247
00:14:34,260 --> 00:14:37,480
phase as the reaction that it's

248
00:14:37,480 --> 00:14:39,710
catalyzing as the reactants.

249
00:14:39,710 --> 00:14:44,310
An example of this is depletion
of the ozone layer

250
00:14:44,310 --> 00:14:46,690
by chlorofluorocarbons.

251
00:14:46,690 --> 00:14:51,860
And so, this was one of the big
environmental challenges

252
00:14:51,860 --> 00:14:56,230
that the U.S. has faced, whether
it should ban these

253
00:14:56,230 --> 00:15:01,380
chlorofluorocarbons, and there
was a lot of debate on what

254
00:15:01,380 --> 00:15:05,360
the data really was about what
how much they affected the

255
00:15:05,360 --> 00:15:06,330
ozone layer.

256
00:15:06,330 --> 00:15:08,710
And I guess that debate is
somewhat still going on,

257
00:15:08,710 --> 00:15:11,580
although I think most people now
recognize that this is a

258
00:15:11,580 --> 00:15:15,640
serious problem and that
legislation is really needed

259
00:15:15,640 --> 00:15:16,960
to help correct it.

260
00:15:16,960 --> 00:15:18,230
So that's an example.

261
00:15:18,230 --> 00:15:21,780
In this case they're all gases,
so that's homogeneous

262
00:15:21,780 --> 00:15:24,650
catalyst, not a happy one.

263
00:15:24,650 --> 00:15:27,380
You could also have
heterogeneous catalysts, which

264
00:15:27,380 --> 00:15:28,760
are a different phase.

265
00:15:28,760 --> 00:15:30,810
And here's another example
that has to do with the

266
00:15:30,810 --> 00:15:31,790
environment.

267
00:15:31,790 --> 00:15:36,510
So a catalytic converter is an
example of a heterogeneous

268
00:15:36,510 --> 00:15:40,500
catalyst. So here you have a
solid metal surface, you can

269
00:15:40,500 --> 00:15:44,860
have palladium or platinum that
will catalyze reactions

270
00:15:44,860 --> 00:15:48,650
with gases, and so they
catalyze oxidation of

271
00:15:48,650 --> 00:15:52,800
hydrocarbons, carbon
monoxide, also

272
00:15:52,800 --> 00:15:55,540
reduction of nitrogen oxide.

273
00:15:55,540 --> 00:15:58,880
So this is all to reduce
pollution.

274
00:15:58,880 --> 00:16:01,690
So that's an example of a
heterogeneous catalyst. And

275
00:16:01,690 --> 00:16:05,450
let me just show you a little
movie of how that might work.

276
00:16:05,450 --> 00:16:10,260
So in this movie, in grey here
we have a metal surface, and

277
00:16:10,260 --> 00:16:14,510
this metal surface can break
the hydrogen bond of h 2.

278
00:16:14,510 --> 00:16:17,570
And so here, it is already
broken, the h 2 bond, so

279
00:16:17,570 --> 00:16:20,270
there's a little hydrogen there
and hydrogen there, and

280
00:16:20,270 --> 00:16:23,630
so that activates the
hydrogen to react.

281
00:16:23,630 --> 00:16:28,130
And so, then we have ethene
molecule come in, and oh,

282
00:16:28,130 --> 00:16:31,060
there goes the hydrogen, and oh,
there goes the hydrogen,

283
00:16:31,060 --> 00:16:33,920
oh, there goes the other one
and you can form ethane.

284
00:16:33,920 --> 00:16:38,640
So it speeds up the reaction
by breaking the h 2 bond so

285
00:16:38,640 --> 00:16:40,810
it's more ready to react.

286
00:16:40,810 --> 00:16:46,970
That would be an example of a
heterogeneous catalyst there.

287
00:16:46,970 --> 00:16:49,900
All right, and, of course, you
may all have guessed that my

288
00:16:49,900 --> 00:16:53,240
favorite kind of catalysts
are enzymes.

289
00:16:53,240 --> 00:16:55,640
They are the catalyst of life.

290
00:16:55,640 --> 00:17:00,170
And so, enzymes are made up of
protein, or mostly protein

291
00:17:00,170 --> 00:17:02,700
molecules -- you can have an
enzyme that's actually made of

292
00:17:02,700 --> 00:17:05,010
RNA, but most are protein
molecules.

293
00:17:05,010 --> 00:17:10,550
And they're typically about
20,000 grams per mole or more,

294
00:17:10,550 --> 00:17:12,120
and they're capable of carrying

295
00:17:12,120 --> 00:17:14,590
out specific reactions.

296
00:17:14,590 --> 00:17:18,400
And so, they're made up of amino
acids, and just to take

297
00:17:18,400 --> 00:17:21,090
a quick look at that, an amino
acid has an amino group and it

298
00:17:21,090 --> 00:17:24,750
has a carboxyl group, and it
has what's called an alpha

299
00:17:24,750 --> 00:17:30,470
carbon that has a side chain on
it, which is abbreviated r,

300
00:17:30,470 --> 00:17:32,570
and there are 20 different
types of r.

301
00:17:32,570 --> 00:17:35,650
The simplest is just a hydrogen,
you could also have

302
00:17:35,650 --> 00:17:37,420
a hydroxide, etc.

303
00:17:37,420 --> 00:17:40,730
And so, this makes up the
alphabet of proteins, there

304
00:17:40,730 --> 00:17:44,030
are 20 different ones of these
that get connected via a

305
00:17:44,030 --> 00:17:45,490
peptide bond.

306
00:17:45,490 --> 00:17:48,750
So at the end of this amino acid
you'd stick on the amino

307
00:17:48,750 --> 00:17:52,580
group of another amino acid and
form this peptide bond.

308
00:17:52,580 --> 00:17:55,860
And then you put together
hundreds and hundreds of these

309
00:17:55,860 --> 00:17:58,850
to form an enzyme complex.

310
00:17:58,850 --> 00:18:03,150
And so, the long chain of amino
acids folds up and forms

311
00:18:03,150 --> 00:18:05,200
a compact structure.

312
00:18:05,200 --> 00:18:09,160
So, in this particular picture,
there are about 200

313
00:18:09,160 --> 00:18:13,940
amino acids in each of these
colored units, so this is a

314
00:18:13,940 --> 00:18:15,800
tetramer, so there are four
-- there's green,

315
00:18:15,800 --> 00:18:19,030
red, yellow and blue.

316
00:18:19,030 --> 00:18:21,920
And so, this is what's called
a ribbon diagram.

317
00:18:21,920 --> 00:18:24,540
So, these ribbons, this is an
alpha helix -- the beta

318
00:18:24,540 --> 00:18:27,170
strands are long.

319
00:18:27,170 --> 00:18:30,500
It traces out the position
of the alpha carbons.

320
00:18:30,500 --> 00:18:34,410
And overall, this structure is
about 90 angstroms by 70

321
00:18:34,410 --> 00:18:38,280
angstroms by 50 angstroms. Of
course, 1 angstroms is 1 times

322
00:18:38,280 --> 00:18:40,120
10 the minus 10 meters.

323
00:18:40,120 --> 00:18:42,420
So these are fairly small.

324
00:18:42,420 --> 00:18:46,370
These protein molecules are,
of course, in your body.

325
00:18:46,370 --> 00:18:52,180
And this particular one is
an enzyme that makes an

326
00:18:52,180 --> 00:18:54,900
antibiotic, and that antibiotic
is fosfomycin,

327
00:18:54,900 --> 00:18:55,950
shown here.

328
00:18:55,950 --> 00:19:02,240
And so, fosfomycin is used
in antibiotic combination

329
00:19:02,240 --> 00:19:07,020
therapies to treat staph
infections and other kinds of

330
00:19:07,020 --> 00:19:09,830
very difficult infections
to treat.

331
00:19:09,830 --> 00:19:13,820
And so, I always talk about
the things that I'm most

332
00:19:13,820 --> 00:19:15,790
concerned about.

333
00:19:15,790 --> 00:19:18,740
There are a lot of things that
are big threats that I don't

334
00:19:18,740 --> 00:19:20,110
worry too much about.

335
00:19:20,110 --> 00:19:22,070
Antibiotic resistance
is something I

336
00:19:22,070 --> 00:19:23,650
actually worry a lot about.

337
00:19:23,650 --> 00:19:25,910
I guess I go to too many
meetings were they talk about

338
00:19:25,910 --> 00:19:30,560
problems. But the rate at
which different kinds of

339
00:19:30,560 --> 00:19:35,680
bacteria are becoming resistant
to antibiotics seems

340
00:19:35,680 --> 00:19:36,990
to be increasing.

341
00:19:36,990 --> 00:19:40,560
So it used to take a lot longer
before a resistance

342
00:19:40,560 --> 00:19:42,660
would appear than it does now.

343
00:19:42,660 --> 00:19:46,820
And there really haven't been,
I think since about 1980s or

344
00:19:46,820 --> 00:19:48,730
so, really new antibiotics.

345
00:19:48,730 --> 00:19:53,560
So, we're still using the same
antibiotics that we have been,

346
00:19:53,560 --> 00:19:57,980
which causes more things to
become immune or resistant to

347
00:19:57,980 --> 00:20:01,370
those antibiotics, and I think
this is really dangerous.

348
00:20:01,370 --> 00:20:04,900
And there's not enough money in
it for the pharmaceutical

349
00:20:04,900 --> 00:20:06,760
industry to really
go after this.

350
00:20:06,760 --> 00:20:10,430
And it's not just a problem
for biological warfare,

351
00:20:10,430 --> 00:20:13,920
although that is a possibility,
but also in

352
00:20:13,920 --> 00:20:18,200
hospitals, you go in for some
kind of surgery, you have to

353
00:20:18,200 --> 00:20:21,300
worry about the fact that even
if the surgery goes great, you

354
00:20:21,300 --> 00:20:24,000
might get an infection that
could really compromise your

355
00:20:24,000 --> 00:20:25,760
health in the hospital.

356
00:20:25,760 --> 00:20:29,760
And so, whether you have a heart
problem, if you have

357
00:20:29,760 --> 00:20:34,160
cancer, you become immune
compromised, there's a lot, a

358
00:20:34,160 --> 00:20:38,560
lot of cases where people end
up not dying of cancer

359
00:20:38,560 --> 00:20:43,390
directly, they end up dying of
the bacterial infection that

360
00:20:43,390 --> 00:20:45,080
can't be treated.

361
00:20:45,080 --> 00:20:47,120
So this is really
a huge problem.

362
00:20:47,120 --> 00:20:49,620
So I always like to let you know
all the possible problems

363
00:20:49,620 --> 00:20:52,050
that you can solve
in your future.

364
00:20:52,050 --> 00:20:55,250
This is one that I think is
particularly important, and I

365
00:20:55,250 --> 00:20:58,620
hope some of you will focus on
this, because we really need

366
00:20:58,620 --> 00:21:00,790
different kinds of antibiotics,
or we need to

367
00:21:00,790 --> 00:21:04,040
change the way we do medicine
in this country so that

368
00:21:04,040 --> 00:21:06,020
resistance doesn't become
as much of a

369
00:21:06,020 --> 00:21:08,670
problem as it has been.

370
00:21:08,670 --> 00:21:13,430
All right, so that enzyme made
an antibiotic, so we like it,

371
00:21:13,430 --> 00:21:16,670
and let's talk about
how that works.

372
00:21:16,670 --> 00:21:20,030
How that particular series of
amino acids folds up to do

373
00:21:20,030 --> 00:21:21,820
that reaction.

374
00:21:21,820 --> 00:21:24,610
So now we have some new
nomenclature, and sometimes

375
00:21:24,610 --> 00:21:27,010
when people get into the
biochemistry world they get

376
00:21:27,010 --> 00:21:28,920
scared because there are all
these words that they don't

377
00:21:28,920 --> 00:21:30,700
know what they mean.

378
00:21:30,700 --> 00:21:33,630
So most of them are not -- they
are things that you can

379
00:21:33,630 --> 00:21:35,470
relate back to something
you already know.

380
00:21:35,470 --> 00:21:38,930
So, we've been talking about
reactants, and when you have a

381
00:21:38,930 --> 00:21:42,270
reactant with an enzyme, it's
usually called a substrate.

382
00:21:42,270 --> 00:21:45,820
So this is just another name
for a reactant molecule.

383
00:21:45,820 --> 00:21:48,440
And then substrates tend to
bind in what we call the

384
00:21:48,440 --> 00:21:50,950
active site of the enzyme,
which is the part of the

385
00:21:50,950 --> 00:21:52,990
enzyme that's going to
do the chemistry.

386
00:21:52,990 --> 00:21:55,400
So those are two terms that
you'll hear about in

387
00:21:55,400 --> 00:21:57,820
biochemistry.

388
00:21:57,820 --> 00:22:01,210
All right, so we have an enzyme,
we'll call it e, it

389
00:22:01,210 --> 00:22:04,660
binds a substrate, we'll call
that s, and then it forms an

390
00:22:04,660 --> 00:22:08,380
enzyme substrate complex,
which we'll call an e s

391
00:22:08,380 --> 00:22:10,800
complex, for enzyme substrate.

392
00:22:10,800 --> 00:22:14,940
And then that enzyme substrate
complex will go to enzyme and

393
00:22:14,940 --> 00:22:16,960
product, which we'll call p.

394
00:22:16,960 --> 00:22:20,190
And if you look in the
state-of-the-art biochemistry

395
00:22:20,190 --> 00:22:22,700
books, these are the
abbreviations you'll see in

396
00:22:22,700 --> 00:22:23,910
there as well.

397
00:22:23,910 --> 00:22:28,170
So, this pains me greatly to
show this cartoon, because I

398
00:22:28,170 --> 00:22:30,700
spend my career determining
3-dimensional structures of

399
00:22:30,700 --> 00:22:33,830
proteins, and so to describe
it as a little squiggly is

400
00:22:33,830 --> 00:22:35,320
painful for me.

401
00:22:35,320 --> 00:22:36,830
But nonetheless, there you go.

402
00:22:36,830 --> 00:22:40,690
Also, the substrate is almost
about as big as the enzyme.

403
00:22:40,690 --> 00:22:42,990
That is also usually not true.

404
00:22:42,990 --> 00:22:45,280
But nonetheless, here's
a little cartoon.

405
00:22:45,280 --> 00:22:48,670
Here's our substrate binding to
our enzyme, it's forming an

406
00:22:48,670 --> 00:22:50,320
e s complex.

407
00:22:50,320 --> 00:22:53,170
And then the enzyme is going
to move the ears of the

408
00:22:53,170 --> 00:22:55,270
substrate around to
form product, and

409
00:22:55,270 --> 00:22:58,490
now product is released.

410
00:22:58,490 --> 00:23:02,130
So, this is actually pretty
simple in terms

411
00:23:02,130 --> 00:23:05,080
of writing a mechanism.

412
00:23:05,080 --> 00:23:08,060
And so, what we can do is write
a mechanism the way that

413
00:23:08,060 --> 00:23:10,160
we have been writing
a mechanism

414
00:23:10,160 --> 00:23:11,620
so far in this class.

415
00:23:11,620 --> 00:23:14,090
And so we're going to go through
this, we're going to

416
00:23:14,090 --> 00:23:17,960
derive expression mostly to show
you that all the things

417
00:23:17,960 --> 00:23:20,350
you've been learning are related
to chemistry, they're

418
00:23:20,350 --> 00:23:22,300
also related to biochemistry.

419
00:23:22,300 --> 00:23:24,770
So, you already know a lot
of biochemistry from just

420
00:23:24,770 --> 00:23:28,590
studying freshman chemistry
in 511-1.

421
00:23:28,590 --> 00:23:31,460
All right, so we have 2 steps
in our mechanism.

422
00:23:31,460 --> 00:23:34,180
We have enzyme binding
substrate to form an

423
00:23:34,180 --> 00:23:38,980
intermediate enzyme substrate
complex, which then goes on to

424
00:23:38,980 --> 00:23:42,000
form enzyme plus product
in step 2.

425
00:23:42,000 --> 00:23:45,510
So the first step is reversible,
the second step is

426
00:23:45,510 --> 00:23:47,070
not as drawn.

427
00:23:47,070 --> 00:23:49,780
All right, so now we can come up
with the rates for each of

428
00:23:49,780 --> 00:23:54,250
the individual steps in this
overall mechanism, and since

429
00:23:54,250 --> 00:23:57,840
they are elementary reactions
or steps in an overall

430
00:23:57,840 --> 00:24:01,180
mechanism, we can write the rate
laws directly from what

431
00:24:01,180 --> 00:24:02,400
we observe.

432
00:24:02,400 --> 00:24:04,270
So for the forward direction,
we're going to

433
00:24:04,270 --> 00:24:07,390
have what rate constant?

434
00:24:07,390 --> 00:24:11,690
K 1 times the concentration
of what?

435
00:24:11,690 --> 00:24:13,440
And?

436
00:24:13,440 --> 00:24:14,450
Yeah.

437
00:24:14,450 --> 00:24:15,120
So there we go.

438
00:24:15,120 --> 00:24:17,790
We have k 1 times the
concentration of e and the

439
00:24:17,790 --> 00:24:19,240
concentration of s.

440
00:24:19,240 --> 00:24:21,620
See, you already knew how
to do biochemistry.

441
00:24:21,620 --> 00:24:26,890
All right, so now at the rate of
the reverse direction is --

442
00:24:26,890 --> 00:24:29,060
what's our rate constant?

443
00:24:29,060 --> 00:24:32,590
K minus 1 times e s.

444
00:24:32,590 --> 00:24:36,690
And then for step 2, we have
what rate constant?

445
00:24:36,690 --> 00:24:41,680
K 2 times e s.

446
00:24:41,680 --> 00:24:44,080
All right, so now we can
talk about the rate

447
00:24:44,080 --> 00:24:46,420
formation of product.

448
00:24:46,420 --> 00:24:50,950
And so you'll see this expressed
as d concentration

449
00:24:50,950 --> 00:24:55,860
of p d t, so the change in
product that's being formed

450
00:24:55,860 --> 00:24:58,650
and that's going to be equal
to the second step

451
00:24:58,650 --> 00:25:01,420
here, k 2 times e s.

452
00:25:01,420 --> 00:25:04,710
But, as has been the case
before, e s is an

453
00:25:04,710 --> 00:25:09,010
intermediate, and we need to
solve our rate laws, our rate

454
00:25:09,010 --> 00:25:11,280
expressions, in terms
of reactants or

455
00:25:11,280 --> 00:25:13,460
products and rate constants.

456
00:25:13,460 --> 00:25:18,150
So we need to solve for
the intermediate.

457
00:25:18,150 --> 00:25:21,600
All right, so let's think
about solving for the

458
00:25:21,600 --> 00:25:22,680
intermediate.

459
00:25:22,680 --> 00:26:27,300
And why don't you tell
me how to do that.

460
00:26:27,300 --> 00:26:42,490
OK, let's just take
10 more seconds.

461
00:26:42,490 --> 00:26:43,110
Very good.

462
00:26:43,110 --> 00:26:46,880
All right, so let's just
take a look at

463
00:26:46,880 --> 00:26:49,940
why that is the case.

464
00:26:49,940 --> 00:26:55,340
So, when we solve for this, it's
going to be equal to the

465
00:26:55,340 --> 00:26:58,800
formation of the intermediate,
which happens in the first

466
00:26:58,800 --> 00:27:01,885
step with this rate that you
told me, k 1 times the

467
00:27:01,885 --> 00:27:03,540
concentration of e s.

468
00:27:03,540 --> 00:27:06,660
And then we have the
decomposition in the reverse

469
00:27:06,660 --> 00:27:11,710
of step one, so that's
minus k minus 1 e s.

470
00:27:11,710 --> 00:27:14,100
And then we also have the
consumption of the

471
00:27:14,100 --> 00:27:18,120
intermediate, which is -- so we
have minus this step, which

472
00:27:18,120 --> 00:27:20,340
is k 2 times e s.

473
00:27:20,340 --> 00:27:24,180
So again, formation minus
decomposition minus

474
00:27:24,180 --> 00:27:26,000
consumption.

475
00:27:26,000 --> 00:27:30,030
And now, we can use the steady
state approximation.

476
00:27:30,030 --> 00:27:32,630
So the steady state
approximation applies in

477
00:27:32,630 --> 00:27:36,550
biochemistry just as well as
in all of your chemistry

478
00:27:36,550 --> 00:27:39,160
problems that you've done
in this course.

479
00:27:39,160 --> 00:27:43,610
And so, the steady state
approximation allows us to set

480
00:27:43,610 --> 00:27:46,250
that whole term equal to zero.

481
00:27:46,250 --> 00:27:51,630
So it says that the net rate of
intermediate formation and

482
00:27:51,630 --> 00:27:56,410
decomposition and consumption is
0, or you can express it as

483
00:27:56,410 --> 00:28:00,770
the rate of formation of the
intermediate equals the rates

484
00:28:00,770 --> 00:28:03,940
of decomposition and consumption
-- those are

485
00:28:03,940 --> 00:28:05,150
equivalent.

486
00:28:05,150 --> 00:28:07,960
So we can set all of
this equal to zero.

487
00:28:07,960 --> 00:28:13,110
So again, the same as what
we've done before.

488
00:28:13,110 --> 00:28:15,520
All right, so now we're going
to have a slight change of

489
00:28:15,520 --> 00:28:18,300
what we've done before, and
this has to do with the

490
00:28:18,300 --> 00:28:20,570
practical consideration.

491
00:28:20,570 --> 00:28:25,850
So you can solve for these
in terms of reactants and

492
00:28:25,850 --> 00:28:30,130
products and rate constants,
but it's actually easier to

493
00:28:30,130 --> 00:28:36,270
solve for e s in terms of your
total enzyme rather than your

494
00:28:36,270 --> 00:28:37,380
free enzyme.

495
00:28:37,380 --> 00:28:40,780
So what we've had before is our
free enzyme, but we often

496
00:28:40,780 --> 00:28:43,880
don't know how much enzyme is
free, and by that we mean not

497
00:28:43,880 --> 00:28:46,010
bound to the substrate.

498
00:28:46,010 --> 00:28:49,570
And so, we know how much total
enzyme we put in, but we might

499
00:28:49,570 --> 00:28:52,010
not know how much of
that is unbound.

500
00:28:52,010 --> 00:28:55,900
So it's actually easier for the
experimentalist to solve

501
00:28:55,900 --> 00:28:58,150
for things in terms
of total enzyme.

502
00:28:58,150 --> 00:29:03,590
And so what we're going to do
then is we're going to replace

503
00:29:03,590 --> 00:29:07,990
our free enzyme term with the
following, total enzyme minus

504
00:29:07,990 --> 00:29:10,840
bound, and total enzyme
minus the bound

505
00:29:10,840 --> 00:29:12,890
enzyme is the free enzyme.

506
00:29:12,890 --> 00:29:16,660
So we're going to do this change
that makes it easier

507
00:29:16,660 --> 00:29:19,750
for the experimentalist.

508
00:29:19,750 --> 00:29:22,720
So here's the term we had
before, but now we want to

509
00:29:22,720 --> 00:29:28,190
replace this term of e with
e to 0 minus e s.

510
00:29:28,190 --> 00:29:31,140
So we're going to put that,
here's the term e up here, so

511
00:29:31,140 --> 00:29:34,420
we're going to replace that
with e 0 minus e s.

512
00:29:34,420 --> 00:29:37,090
And then we're going to multiply
that out, so we get k

513
00:29:37,090 --> 00:29:44,460
1, e 0, s minus k 1, e s, and
then the concentration of

514
00:29:44,460 --> 00:29:46,940
substrate here, and the rest
of it is the same.

515
00:29:46,940 --> 00:29:50,920
So we got rid of our term e.

516
00:29:50,920 --> 00:29:55,140
So now we can solve for e s.

517
00:29:55,140 --> 00:29:58,110
So this is what we just had,
and so we're going to

518
00:29:58,110 --> 00:30:01,670
rearrange so the e s terms are
on one side, so we have an e s

519
00:30:01,670 --> 00:30:03,200
term here, here, and here.

520
00:30:03,200 --> 00:30:05,810
So all that is going to be on
one side, and then this other

521
00:30:05,810 --> 00:30:08,820
term will be on the other
side of the equation.

522
00:30:08,820 --> 00:30:12,180
So now we have moved all the e
s terms over here, so we've

523
00:30:12,180 --> 00:30:14,390
got rid of the negative numbers,
we've added them all

524
00:30:14,390 --> 00:30:17,590
to the other side, and then on
this side we just have this k

525
00:30:17,590 --> 00:30:19,280
1 term left.

526
00:30:19,280 --> 00:30:23,030
Now we're going to pull
out the e s terms. So,

527
00:30:23,030 --> 00:30:24,830
we'll solve for e s.

528
00:30:24,830 --> 00:30:28,450
We'll pull that out, that leaves
us with k 1 times the

529
00:30:28,450 --> 00:30:32,810
concentration of s, k minus
1, and then k 2.

530
00:30:32,810 --> 00:30:36,650
And now we're going to take this
and divide by that term

531
00:30:36,650 --> 00:30:41,630
in parentheses, and so now we've
solved for e s in terms

532
00:30:41,630 --> 00:30:46,250
of total enzyme substrate
and our rate constants.

533
00:30:46,250 --> 00:30:47,780
All right, now we're going
to do another thing

534
00:30:47,780 --> 00:30:49,050
that's a bit different.

535
00:30:49,050 --> 00:30:52,680
We're going to introduce a term
in biochemistry, which is

536
00:30:52,680 --> 00:30:57,560
k m, also known as the
Michaelis-Menten constant, and

537
00:30:57,560 --> 00:31:01,570
so k m is equal to the
rate constant for the

538
00:31:01,570 --> 00:31:08,290
forward/reverse direction, k
minus 1 plus k 2 over k 1.

539
00:31:08,290 --> 00:31:14,180
So we're going to now try to
use this in our expression.

540
00:31:14,180 --> 00:31:19,820
So we're going to put this term
in there, and so to have

541
00:31:19,820 --> 00:31:23,630
this term of k m in there,
we need to have this

542
00:31:23,630 --> 00:31:25,500
divided by k 1.

543
00:31:25,500 --> 00:31:28,740
So we can do that, it's OK, as
long as we divide everything

544
00:31:28,740 --> 00:31:32,160
by k 1, so we're going to divide
the top by k 1, and

545
00:31:32,160 --> 00:31:35,090
this by k 1, and that by k 1.

546
00:31:35,090 --> 00:31:41,070
So now, we divide all by k 1,
and so we have this top with k

547
00:31:41,070 --> 00:31:44,370
1, this term with k 1, and
this with k 1, and

548
00:31:44,370 --> 00:31:46,130
that's our k m value.

549
00:31:46,130 --> 00:31:49,850
But now we can simplify this,
we've got a lot of k 1's here,

550
00:31:49,850 --> 00:31:53,380
and so if we simplify this,
we can cross out

551
00:31:53,380 --> 00:31:56,320
those k 1's over there.

552
00:31:56,320 --> 00:32:00,470
And we can also get rid of
these k 1's over here.

553
00:32:00,470 --> 00:32:02,810
And that's going to leave
us with a much simpler

554
00:32:02,810 --> 00:32:03,960
expression.

555
00:32:03,960 --> 00:32:07,450
So that's going to leave us with
the total enzyme times

556
00:32:07,450 --> 00:32:11,770
substrate over substrate
plus k m.

557
00:32:11,770 --> 00:32:14,430
And that looks a whole lot
better than that other term

558
00:32:14,430 --> 00:32:21,550
that we had before.

559
00:32:21,550 --> 00:32:25,780
OK, so we can now take this and
substitute it back into

560
00:32:25,780 --> 00:32:29,480
the expression we had earlier.

561
00:32:29,480 --> 00:32:34,140
So here we had the rate of
product formation, k 2 times

562
00:32:34,140 --> 00:32:38,160
this intermediate, we solved
for the intermediate using

563
00:32:38,160 --> 00:32:41,580
total enzyme and using
this k m term.

564
00:32:41,580 --> 00:32:45,280
And now we just put all
of this times k 2.

565
00:32:45,280 --> 00:32:48,630
And if you put all of that
times k 2, you have this

566
00:32:48,630 --> 00:32:52,900
expression, which is the
Michaelis-Menten equation.

567
00:32:52,900 --> 00:32:56,460
So the only difference of what
you did before was that you

568
00:32:56,460 --> 00:33:00,560
solved in terms of total enzyme,
and also, we have this

569
00:33:00,560 --> 00:33:03,130
new k m term.

570
00:33:03,130 --> 00:33:06,360
And so now we have an equation
that's used in a lot of

571
00:33:06,360 --> 00:33:12,510
biochemistry research to think
about enzyme kinetics.

572
00:33:12,510 --> 00:33:15,370
So let's think about enzyme
kinetics for a minute.

573
00:33:15,370 --> 00:33:18,700
This is what a plot often looks
like -- we are looking

574
00:33:18,700 --> 00:33:21,640
at the product formed by
an enzyme versus the

575
00:33:21,640 --> 00:33:23,440
concentration of substrate.

576
00:33:23,440 --> 00:33:24,800
And it often goes up.

577
00:33:24,800 --> 00:33:28,210
It's pretty steep, and then
it starts to level off.

578
00:33:28,210 --> 00:33:31,530
So let's think about what's
happening here.

579
00:33:31,530 --> 00:33:35,620
So if you have low substrate,
so that's way down here, not

580
00:33:35,620 --> 00:33:39,800
much substrate is available,
adding more substrate will

581
00:33:39,800 --> 00:33:42,090
increase this rate
significantly, you'll form a

582
00:33:42,090 --> 00:33:45,690
lot more product, it increases
the rate of product formation.

583
00:33:45,690 --> 00:33:47,950
Because a lot of the
enzyme is free and

584
00:33:47,950 --> 00:33:49,610
can react with substrate.

585
00:33:49,610 --> 00:33:53,360
So it goes up, but then the
rate starts to level off.

586
00:33:53,360 --> 00:33:58,230
So when you got to higher
substrate concentrations,

587
00:33:58,230 --> 00:34:02,562
adding more substrate does not
affect the rate much, the rate

588
00:34:02,562 --> 00:34:03,750
is leveling off.

589
00:34:03,750 --> 00:34:06,480
And we say that the enzyme
is saturated.

590
00:34:06,480 --> 00:34:10,060
All the enzyme that you have in
there already has substrate

591
00:34:10,060 --> 00:34:12,450
going on, it's already
doing the chemistry.

592
00:34:12,450 --> 00:34:15,800
So if you're throwing more at
it, the enzyme can't bind that

593
00:34:15,800 --> 00:34:19,010
substrate, it's busy with a
different substrate molecule.

594
00:34:19,010 --> 00:34:23,140
So all the active sites in the
enzyme are full, and so not

595
00:34:23,140 --> 00:34:24,220
much happens.

596
00:34:24,220 --> 00:34:28,320
So this kind of graph
is what you often

597
00:34:28,320 --> 00:34:32,050
see in enzyme kinetics.

598
00:34:32,050 --> 00:34:34,130
Now let's think about
that in terms of our

599
00:34:34,130 --> 00:34:34,410
Michaelis-Menten equation.

600
00:34:34,410 --> 00:34:40,050
So let's think about conditions
when there's a lot

601
00:34:40,050 --> 00:34:44,990
of substrate, when substrate
is much greater than k m.

602
00:34:44,990 --> 00:34:48,370
So here we have substrate and
k m on the bottom of our

603
00:34:48,370 --> 00:34:52,490
equation, and what's going to
happen if this term is much,

604
00:34:52,490 --> 00:34:56,230
much bigger than
this k m term?

605
00:34:56,230 --> 00:35:00,040
What happens to the k m term?

606
00:35:00,040 --> 00:35:01,550
It goes away.

607
00:35:01,550 --> 00:35:04,380
It's really small compared
to this, it's kind of

608
00:35:04,380 --> 00:35:06,040
insignificant.

609
00:35:06,040 --> 00:35:10,800
So, if that happens, then you
can cancel substrate as well.

610
00:35:10,800 --> 00:35:13,830
And so, that means that under
conditions where substrate is

611
00:35:13,830 --> 00:35:18,190
much greater than k m, the rate
is a much simpler term,

612
00:35:18,190 --> 00:35:22,250
it's just equal to k 2 times
your total enzyme.

613
00:35:22,250 --> 00:35:26,650
And so this has a name, this is
called Vmax or the maximum

614
00:35:26,650 --> 00:35:29,130
velocity of the reaction.

615
00:35:29,130 --> 00:35:32,030
So, under these conditions,
when the substrate is much

616
00:35:32,030 --> 00:35:36,490
greater than that k m value,
this expression simplifies and

617
00:35:36,490 --> 00:35:40,530
you get just k 2, your rate
constant, times your total

618
00:35:40,530 --> 00:35:43,490
enzyme, and that'll give
you the maximum

619
00:35:43,490 --> 00:35:47,250
velocity of the reaction.

620
00:35:47,250 --> 00:35:49,670
And so, that's just written
again here.

621
00:35:49,670 --> 00:35:53,440
Vmax equals k 2 times total
enzyme, and that equation will

622
00:35:53,440 --> 00:35:55,810
be given to you on an
equation sheet.

623
00:35:55,810 --> 00:35:56,750
So what's happening?

624
00:35:56,750 --> 00:35:58,800
What's happening is that
you're up here.

625
00:35:58,800 --> 00:36:02,460
So when substrate concentration
is much greater

626
00:36:02,460 --> 00:36:06,190
than k m, then you're in these
conditions, and you're at some

627
00:36:06,190 --> 00:36:07,390
maximum velocity.

628
00:36:07,390 --> 00:36:10,550
So the velocity will only go,
the rate of the reaction will

629
00:36:10,550 --> 00:36:14,510
only go so fast, it will
saturate, it'll level off up

630
00:36:14,510 --> 00:36:16,910
here, and so you can calculate
that maximum

631
00:36:16,910 --> 00:36:20,520
rate of that reaction.

632
00:36:20,520 --> 00:36:24,110
Now let's consider what happens
when your substrate

633
00:36:24,110 --> 00:36:27,800
concentration equals your k m.

634
00:36:27,800 --> 00:36:32,900
So down here, if k m is equal to
substrate, then we're going

635
00:36:32,900 --> 00:36:36,540
to have two substrates
down here.

636
00:36:36,540 --> 00:36:39,590
And so, we can write this, if
they're equal, we can write

637
00:36:39,590 --> 00:36:44,390
this as substrate plus
substrate, and then we can do

638
00:36:44,390 --> 00:36:46,950
some canceling.

639
00:36:46,950 --> 00:36:50,920
So this will be equal to 2
substrates and then we can

640
00:36:50,920 --> 00:36:54,580
cancel that out, and so we get
the rate of product formation

641
00:36:54,580 --> 00:36:59,270
under conditions where substrate
equals k m of 1/2 k

642
00:36:59,270 --> 00:37:04,290
2 times the total enzyme
concentration.

643
00:37:04,290 --> 00:37:07,760
And this is referred to
the half maximal rate.

644
00:37:07,760 --> 00:37:13,320
Remember, the maximal rate was
k 2 times this e knot, and so

645
00:37:13,320 --> 00:37:18,350
half of that is half the
maximal rate here.

646
00:37:18,350 --> 00:37:24,210
So, the definition of k m is the
concentration of substrate

647
00:37:24,210 --> 00:37:28,120
for which the rate
is half maximal.

648
00:37:28,120 --> 00:37:32,070
So if your rate is half of the
maximum rate, that substrate

649
00:37:32,070 --> 00:37:36,470
concentration that gives you
half the maximum rate, is the

650
00:37:36,470 --> 00:37:38,440
value for k m.

651
00:37:38,440 --> 00:37:44,370
Substrate concentration equals
k m at the half maximal rate.

652
00:37:44,370 --> 00:37:45,990
So let's just look at
what that meant.

653
00:37:45,990 --> 00:37:52,780
So if this is Vmax up here, half
of Vmax is here, half of

654
00:37:52,780 --> 00:37:58,030
that value, and the substrate
concentration at half Vmax is

655
00:37:58,030 --> 00:37:59,850
equal to k m.

656
00:37:59,850 --> 00:38:03,400
So you can write those
in on your diagram.

657
00:38:03,400 --> 00:38:07,610
Vmax is this velocity up here,
half of that, when you're at

658
00:38:07,610 --> 00:38:12,120
half of the maximal rate,
k m equals the substrate

659
00:38:12,120 --> 00:38:14,190
concentration.

660
00:38:14,190 --> 00:38:17,180
And there will be problems that
you will work in your

661
00:38:17,180 --> 00:38:22,070
book very shortly, and often,
the problems just have to do,

662
00:38:22,070 --> 00:38:25,090
they'll give you the information
in words and the

663
00:38:25,090 --> 00:38:27,870
calculations can often
be pretty simple.

664
00:38:27,870 --> 00:38:31,780
Sometimes it'll say, figure
out what the k m for this

665
00:38:31,780 --> 00:38:32,970
reaction is.

666
00:38:32,970 --> 00:38:35,060
At this substrate concentration,
the rate is

667
00:38:35,060 --> 00:38:35,960
half maximal.

668
00:38:35,960 --> 00:38:39,140
Well, at that substrate
concentration, that's the k m.

669
00:38:39,140 --> 00:38:42,090
So, a lot of the problems are
sort of word problems, they

670
00:38:42,090 --> 00:38:44,180
give you the information and
you need to know what the

671
00:38:44,180 --> 00:38:46,390
definitions are.

672
00:38:46,390 --> 00:38:48,280
But let's try an example.

673
00:38:48,280 --> 00:38:54,460
So here in this example, we've
talked about buffering in the

674
00:38:54,460 --> 00:39:00,360
blood, so the conversion of
your ingredients that make

675
00:39:00,360 --> 00:39:04,820
your buffering agent in the
blood, that can be catalyzed

676
00:39:04,820 --> 00:39:08,900
by an enzyme called
carbonicanhydrase, and the

677
00:39:08,900 --> 00:39:13,380
following Michaelis-Menten
constants are known, a k m is

678
00:39:13,380 --> 00:39:18,570
known, and a k 2 is known, and
if you're doing experiment and

679
00:39:18,570 --> 00:39:22,740
you have a total concentration
of your enzyme of 5 times 10

680
00:39:22,740 --> 00:39:26,970
to the minus 6 molar, then you
should be able to figure out

681
00:39:26,970 --> 00:39:31,390
what the maximum rate of
the reaction would be.

682
00:39:31,390 --> 00:39:33,120
So, why don't you go ahead
and tell me what the

683
00:39:33,120 --> 00:40:34,580
maximum rate would be.

684
00:40:34,580 --> 00:40:49,520
OK, let's just take
10 more seconds.

685
00:40:49,520 --> 00:40:49,950
Very good.

686
00:40:49,950 --> 00:40:51,510
Everyone's doing very
good today.

687
00:40:51,510 --> 00:40:57,030
All right, so all you have to
do, you have remember Vmax

688
00:40:57,030 --> 00:41:01,740
equals your total enzyme
concentration times your k 2.

689
00:41:01,740 --> 00:41:05,440
And pretty much no one, hardly
anyone was fooled

690
00:41:05,440 --> 00:41:07,500
by k m value there.

691
00:41:07,500 --> 00:41:11,380
All right, very good.

692
00:41:11,380 --> 00:41:16,840
So there are extra problems on
enzyme kinetics posted on the

693
00:41:16,840 --> 00:41:18,890
extra problems posted
on the Web.

694
00:41:18,890 --> 00:41:22,180
So there's a few there, so you
can see the type of problems,

695
00:41:22,180 --> 00:41:24,580
again, they're like that,
they're pretty simple.

696
00:41:24,580 --> 00:41:27,950
If you remember the definition
of k m, and you'll be given

697
00:41:27,950 --> 00:41:31,990
the equation for Vmax, you
should be able to handle the

698
00:41:31,990 --> 00:41:35,040
enzyme/kinetics problems
pretty well.

699
00:41:35,040 --> 00:41:39,880
Often, also I'll ask questions
like explain why at high

700
00:41:39,880 --> 00:41:44,220
substrate concentrations, the
rate does not increase very

701
00:41:44,220 --> 00:41:48,770
much, or why the graph levels
off, or I might ask you to

702
00:41:48,770 --> 00:41:52,290
draw the plot and tell me
about low substrate

703
00:41:52,290 --> 00:41:55,280
concentrations, what's true
there, and high substrate

704
00:41:55,280 --> 00:41:56,860
concentrations, what's true.

705
00:41:56,860 --> 00:41:58,870
So those are the types of
questions you're going to get

706
00:41:58,870 --> 00:42:03,230
on enzyme kinetics, they're
actually pretty simple.

707
00:42:03,230 --> 00:42:05,990
All right, so let's just talk
briefly about enzyme

708
00:42:05,990 --> 00:42:07,230
inhibition.

709
00:42:07,230 --> 00:42:10,750
So the opposite of catalysis
-- instead of binding a

710
00:42:10,750 --> 00:42:13,790
substrate, you'll bind
an inhibitor.

711
00:42:13,790 --> 00:42:19,020
So often, these are actually
pretty simple.

712
00:42:19,020 --> 00:42:22,410
An inhibitor sometimes will look
a lot like a substrate or

713
00:42:22,410 --> 00:42:26,180
like a transition complex, and
it'll blind to the enzyme.

714
00:42:26,180 --> 00:42:29,050
And when you have that inhibitor
stuck in the active

715
00:42:29,050 --> 00:42:33,310
site, substrate physically can't
bind, so it occupies the

716
00:42:33,310 --> 00:42:36,600
place that substrate goes,
substrate will come in but it

717
00:42:36,600 --> 00:42:38,030
can't bind anywhere.

718
00:42:38,030 --> 00:42:42,210
So this is actually the
mechanism by which a number of

719
00:42:42,210 --> 00:42:44,780
pharmaceuticals work.

720
00:42:44,780 --> 00:42:49,870
So, one thing that people who
were designing enzyme

721
00:42:49,870 --> 00:42:56,230
inhibitors think about is the
fact that enzymes do tend to

722
00:42:56,230 --> 00:43:00,420
stabilize a transition state
in the reaction.

723
00:43:00,420 --> 00:43:05,790
So if you make an inhibitor that
resembles a transition

724
00:43:05,790 --> 00:43:10,400
state, it should bind to the
enzyme more tightly than

725
00:43:10,400 --> 00:43:14,530
either the reactants, the
substrates, or the products.

726
00:43:14,530 --> 00:43:17,560
So, a lot of the pharmaceutical
industry likes

727
00:43:17,560 --> 00:43:20,900
to try to figure out what the
transition state might look

728
00:43:20,900 --> 00:43:24,710
like, and then try to make a
molecule that looks like that

729
00:43:24,710 --> 00:43:27,450
transition state that hopefully
will blind to the

730
00:43:27,450 --> 00:43:31,710
enzyme active site and prevent
the enzyme from doing what

731
00:43:31,710 --> 00:43:35,030
it's supposed to do.

732
00:43:35,030 --> 00:43:38,630
So, just to kind of look back
at this figure for a minute

733
00:43:38,630 --> 00:43:41,720
that you had earlier in your
notes, so you have the

734
00:43:41,720 --> 00:43:46,390
transition state is often
stabilized by a catalyst, and

735
00:43:46,390 --> 00:43:50,650
so an enzyme will also stabilize
a transition state.

736
00:43:50,650 --> 00:43:53,870
So if you make your drug look
like a transition state, it

737
00:43:53,870 --> 00:43:56,560
will hopefully bind
very tightly.

738
00:43:56,560 --> 00:44:02,380
And so this is one of the sort
of principles that's behind a

739
00:44:02,380 --> 00:44:06,490
lot of the pharmaceuticals that
have made to treat HIV

740
00:44:06,490 --> 00:44:07,330
infections.

741
00:44:07,330 --> 00:44:11,320
So I mentioned last week we
had world AIDS day, that

742
00:44:11,320 --> 00:44:13,550
understanding kinetics
was actually very

743
00:44:13,550 --> 00:44:16,970
important in HIV research.

744
00:44:16,970 --> 00:44:19,730
And so, many of the
pharmaceuticals that are given

745
00:44:19,730 --> 00:44:23,720
to HIV patients are what are
called protease inhibitors.

746
00:44:23,720 --> 00:44:27,480
So they inhibit enzymes that are
called proteases, and if

747
00:44:27,480 --> 00:44:30,120
you have ase at the end of the
name that means it's an

748
00:44:30,120 --> 00:44:34,220
enzyme, and so protease means
that it's an enzyme that

749
00:44:34,220 --> 00:44:35,720
cleaves proteins.

750
00:44:35,720 --> 00:44:37,590
It's a protein ase.

751
00:44:37,590 --> 00:44:40,450
And so, how do these
enzymes work.

752
00:44:40,450 --> 00:44:43,130
Well, they cleave other
proteins, they cleave peptide

753
00:44:43,130 --> 00:44:46,040
bonds, and so you often have
some kind of either activated

754
00:44:46,040 --> 00:44:51,650
water or other hydroxide
molecule that will attack here

755
00:44:51,650 --> 00:44:55,700
the carbonyl of a peptide
bond, and it forms a

756
00:44:55,700 --> 00:44:59,180
tetrahedral intermediate, which
then collapses and it

757
00:44:59,180 --> 00:45:00,350
cleaves that peptide bond.

758
00:45:00,350 --> 00:45:03,210
So the peptide bond is then
broken, so that's what a

759
00:45:03,210 --> 00:45:06,800
protease does, and a
protease inhibitor

760
00:45:06,800 --> 00:45:08,470
prevents that cleavage.

761
00:45:08,470 --> 00:45:12,030
So often, protease inhibitors
look like tetrahedral

762
00:45:12,030 --> 00:45:15,800
intermediates, and so they'll
bind to the protease active

763
00:45:15,800 --> 00:45:18,920
site and prevent the chemistry
from occurring.

764
00:45:18,920 --> 00:45:21,570
So if it's a tetrahedral
intermediate, what kind of

765
00:45:21,570 --> 00:45:24,230
angles should some
pharmaceutical company be

766
00:45:24,230 --> 00:45:26,650
looking for in its compounds?

767
00:45:26,650 --> 00:45:28,570
109 .

768
00:45:28,570 --> 00:45:30,320
5, yes.

769
00:45:30,320 --> 00:45:36,280
So, molecules with this stable
tetrahedral intermediate

770
00:45:36,280 --> 00:45:41,030
somewhere on the molecule could
bind to the active site

771
00:45:41,030 --> 00:45:43,110
and prevent a catalysis.

772
00:45:43,110 --> 00:45:46,900
So, let me just show you one
example of an improved HIV

773
00:45:46,900 --> 00:45:48,880
drug, and there it is.

774
00:45:48,880 --> 00:45:54,470
This is the tetrahedral site
that binds at the active site

775
00:45:54,470 --> 00:45:58,950
of that enzyme, and the enzyme
can't cleave this tetrahedral

776
00:45:58,950 --> 00:46:02,280
intermediate, and so this just
binds, but the enzyme can't

777
00:46:02,280 --> 00:46:06,980
work on it, so it just sits
there and prevents substrate

778
00:46:06,980 --> 00:46:08,080
from binding.

779
00:46:08,080 --> 00:46:12,300
So that's how a lot of
these compounds work.

780
00:46:12,300 --> 00:46:15,580
And so, this is just a little
picture of the enzyme active

781
00:46:15,580 --> 00:46:19,490
site and there's an inhibitor
bound to the enzyme active

782
00:46:19,490 --> 00:46:21,980
site, and so a number of
companies are working on

783
00:46:21,980 --> 00:46:24,920
trying to come up with better
and better inhibitors that

784
00:46:24,920 --> 00:46:28,710
will sit in the HIV protease
active site.

785
00:46:28,710 --> 00:46:33,410
So, knowledgeable of a reaction
mechanism can lead to

786
00:46:33,410 --> 00:46:35,960
new therapeutic treatments.

787
00:46:35,960 --> 00:46:39,760
So, one question with this, with
protease, there are a lot

788
00:46:39,760 --> 00:46:43,320
of proteases, not just the ones
involved with HIV, and so

789
00:46:43,320 --> 00:46:47,120
one real problem is specificity
and toxicity, so

790
00:46:47,120 --> 00:46:50,850
you want to have a drug that
inhibits one enzyme and not

791
00:46:50,850 --> 00:46:53,100
all the enzymes in
that category.

792
00:46:53,100 --> 00:46:56,910
So that's a big problem in the
pharmaceutical industry.

793
00:46:56,910 --> 00:47:02,540
So, apparently, clicker results,
we actually need to

794
00:47:02,540 --> 00:47:07,830
break a tie.

795
00:47:07,830 --> 00:47:11,830
But we can't do it now.

796
00:47:11,830 --> 00:47:19,250
OK, so Justin's section, woah!

797
00:47:19,250 --> 00:47:22,580
So, apparently we're having, we
have the questions ready,

798
00:47:22,580 --> 00:47:25,200
but apparently they're
not ready to be used

799
00:47:25,200 --> 00:47:26,820
right at the moment.

800
00:47:26,820 --> 00:47:32,630
So, we're going to use low tech
here and indicate the

801
00:47:32,630 --> 00:47:36,030
results for today.

802
00:47:36,030 --> 00:47:42,720
And then on Wednesday, last
day of class -- oh, my

803
00:47:42,720 --> 00:47:46,400
goodness, so close.

804
00:47:46,400 --> 00:47:57,960
Recitation 6, you were second.

805
00:47:57,960 --> 00:48:02,310
All right, so on Wednesday then,
we're going to have the

806
00:48:02,310 --> 00:48:06,180
tie breaker, and review
and evaluations.