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PROFESSOR: Today is our
final clicker competition.

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The first question is up.
 

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And I would just like to go
over the current standing for

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the clicker competition as
we're getting started here.

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

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

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and 10 have one win.
 

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If any of those recitation wins
today, we're going to go to

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a tie breaker to decide the
overall recitation champion.

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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, but

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they will have snacks, and they
will assure that recitations 2,

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

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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

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and different sizes.
 

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All right, so time to
get started with the

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clicker 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 activation

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energy today.
 

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

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we're going to start with the
material that we didn't quite

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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 about

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what we learned before in
a slightly different way.

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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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sort of -- you know it's not
too intuitive to MIT students,

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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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But we're back to talking
about minimizing stress.

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And we talked about adding
reagents and removing products,

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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

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temperature has changed.
 

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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

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to 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.
 

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So, on one axis we have
p e plotted -- what

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does that stand for?
 

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Potential energy, right, so
we have potential energy

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going up 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 products,

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we have a delta e between
those, and we have a very large

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activation energy barrier
for the forward direction.

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

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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 have

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to sort of distort bonds and
sort of rearrange things, and

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that takes a certain
amount of energy.

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So if they come together and
they have that energy, they'll

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react and go on to products, if
they don't they'll break apart

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and go back and be reactants.
 

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And how much temperature the
system has, is more likely that

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they'll be able to react.
 

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

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overcome this activation
energy barrier.

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All right, so in an endothermic
reaction, you have a big one in

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the forward direction, and a
much smaller activation energy

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in the reverse direction.
 

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For exothermic reaction it's
the reverse -- there's a

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smaller barrier for the
forward direction, and a

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much larger barrier for
the reverse direction.

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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

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gases is 1% or 2% different.
 

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So you have a positive value
here, and you can get a

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positive delta e here if you
have a big number for the

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forward activation energy
barrier minus a small number

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for the reverse, so that's
going to give you a

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positive number.
 

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For an exothermic reaction,
delta e's going to be negative,

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and you get a negative number
if you take a small number here

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for the forward activation
energy, and subtract it from a

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larger number here for the
reverse activation energy.

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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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it's part of understanding
what's going on in

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these diagrams.
 

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So now let's think about what
increasing the temperature

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is 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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for the molecules to get over
them, regardless of

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the temperature.
 

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But when the barrier is big,
then temperature is going

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to make a big difference.
 

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And you can sort of think about
this in your own life as you

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have a small assignment to do,
you just jump in and do it and

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get it done and it's fine.
 

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But if it's a very, very large
thing that you have to do, you

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often need to procrastinate
longer before you

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start doing it.
 

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So, a small barrier's not so
much of a problem, but if it's

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a big barrier, you need to
increase that temperature

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to help the molecules get
over the bigger barriers.

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So, let's think about what this
means in terms of the direction

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that a reaction might shift.
 

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So, if you increase a
temperature over here with an

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endothermic reaction, it makes
it easier to overcome

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the bigger barrier.
 

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The forward reaction barrier is
the bigger one, so increasing

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the temperature will help
molecules get over

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that barrier.
 

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They're already doing fine with
the reverse barrier, it's the

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forward barrier that we're
having trouble with.

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So, if you increase the
temperature, that's going to

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shift the equilibrium toward
products, or it will shift

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the reaction in the
endothermic direction.

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That's what we had learned
before with LeChatelier's

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principle, but now there's
a new way of thinking

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about why that is true.
 

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So, for an exothermic reaction,
if you increase the

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temperature, that helps
with the bigger barrier.

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Again, here the bigger barrier
is for the reverse reaction.

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So, if you increase the
temperature of an exothermic

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reaction, it's going to
shift it toward reactants.

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More molecules can overcome
that reverse barrier, and so

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you'll form more reactants,
it'll shift toward reactants

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or it'll shift in the
endothermic direction.

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Again, these are the same
things that we already knew

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from LeChatelier, but it's a
different way of thinking about

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why those things are true.
 

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So, a large activation energy
barrier means that rate

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constants are very
sensitive to temperature.

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And so, if you have a big
activation energy barrier,

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increasing the temperature
makes a big difference -- if

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it's a big barrier, then
there's going to have a big

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difference if you have
higher temperature.

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If it's a small barrier, then
increasing the temperature

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doesn't make much
of a difference.

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And so you can think about
that in terms of these

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diagrams as well.
 

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So, now we're done with
temperature and we're going

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to talk about catalysis
and the use of catalysts.

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And so, if you remember there
were factors affecting the

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reaction, and we've talked
about everything on this

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list except for catalysts.
 

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So today we're going to
talk about catalysts.

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So, a catalyst is a substance
that speeds up a reaction, but

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it doesn't get consumed in the
reaction, it doesn't undergo

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any permanent change itself.
 

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It's just added to
speed up the reaction.

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So catalysts do not appear in
the overall balanced equation.

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So let's look at what a
catalyst is going to do, and

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we're going to look at in
terms of these potential

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energy diagrams as well.
 

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So here we here we have
a reaction, we're going

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from reactants down
here to products.

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We have the delta e for the
reaction, we have a forward

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activation energy barrier
and a reverse one.

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So, up here, at the top, that's
our barrier without a catalyst.

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This is the transition state or
the activated complex up here,

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so you have to overcome the
barrier, you form some kind of

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activated complex, which then,
if there's enough energy to

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overcome that barrier,
goes on to products.

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So when you add a catalyst
what happens is it

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lowers this barrier.
 

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So, in the blue line here
is the new activation

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energy barrier.
 

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This is the barrier with a
catalyst, and so this would

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then be the new transition
state with a catalyst.

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So when it lowers the barrier,
it's going to lower the barrier

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for the forward reaction, so we
have a new activation energy

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for the forward reaction, and
we're going to have a new

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activation energy for
the reverse direction.

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So catalysts work by reducing
both the forward and the

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reverse activation
energy barrier.

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And another way that you can
say this is that they stabilize

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the activated complex or
the transition state.

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So here you have an activated
complex with a much higher

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potential energy without the
catalysts, and by stabilizing,

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you lower in energy
that transition state.

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So that's another way
of expressing what

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a catalyst does.
 

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So, catalysts have no effect on
the thermodynamics of the

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reaction, they affect the
kinetics of the reaction,

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but they don't affect the
thermodynamics of the reaction.

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And so, of course, when you
think of thermodynamics, you

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often think of delta g.
 

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So, why don't you tell me what
you think, what would happen

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about, so delta g is a state
function, it's independent of

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path, and so therefore, what
can you tell me about the

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equilibrium constant in the
presence of a catalyst?

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OK, let's just take
10 more seconds.

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Yup, very good.
 

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So, the equilibrium
constant is not changed.

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The thermodynamics, which
includes delta g and the

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equilibrium constant are not
affected, the rates of the

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reaction are affected.
 

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All right, so opposite of a
catalyst is an inhabitor, and

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we'll talk more about this at
the end of class, so it would

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-- inhibitor is slow or
sometimes stop the rate of the

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reaction, and one way that they
do this is by increasing

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the activation energy.
 

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So let's consider types
of catalysts now.

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You can have a homogeneous
catalyst, which is in the same

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phase as the reaction that it's
catalyzing as the reactants.

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An example of this is depletion
of the ozone layer by

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chlorofluorocarbons.
 

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And so, this was one of the big
environmental challenges that

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the U.S. has faced, whether it
should ban these

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chlorofluorocarbons, and there
was a lot of debate on what the

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data really was about what how
much they affected

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the ozone layer.
 

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And I guess that debate is
somewhat still going on,

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although I think most people
now recognize that this is a

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serious problem and that
legislation is really

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needed to help correct it.
 

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So that's an example.
 

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In this case they're all
gases, so that's homogeneous

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catalyst, not a happy one.
 

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You could also have
heterogeneous catalysts,

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which are a different phase.
 

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And here's another example that
has to do with the environment.

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So a catalytic converter
is an example of a

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00:15:35 --> 00:15:37
heterogeneous catalyst.
 

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So here you have a solid metal
surface, you can have palladium

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or platinum that will catalyze
reactions with gases, and so

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they catalyze oxidation of
hydrocarbons, carbon monoxide,

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also reduction of
nitrogen oxide.

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So this is all to
reduce pollution.

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So that's an example of a
heterogeneous catalyst.

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And let me just show
you a little movie of

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how that might work.
 

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So in this movie, in grey here
we have a metal surface, and

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this metal surface can break
the hydrogen bond of h 2.

272
00:16:14 --> 00:16:17
And so here, it is already
broken, the h 2 bond, so

273
00:16:17 --> 00:16:20
there's a little hydrogen there
and hydrogen there, and so

274
00:16:20 --> 00:16:23
that activates the
hydrogen to react.

275
00:16:23 --> 00:16:28
And so, then we have ethene
molecule come in, and oh, there

276
00:16:28 --> 00:16:31
goes the hydrogen, and oh,
there goes the hydrogen, oh,

277
00:16:31 --> 00:16:33
there goes the other one
and you can form ethane.

278
00:16:33 --> 00:16:38
So it speeds up the reaction
by breaking the h 2 bond so

279
00:16:38 --> 00:16:40
it's more ready to react.
 

280
00:16:40 --> 00:16:46
That would be an example of a
heterogeneous catalyst there.

281
00:16:46 --> 00:16:49
All right, and, of course,
you may all have guessed

282
00:16:49 --> 00:16:53
that my favorite kind of
catalysts are enzymes.

283
00:16:53 --> 00:16:55
They are the catalyst of life.
 

284
00:16:55 --> 00:17:00
And so, enzymes are made up of
protein, or mostly protein

285
00:17:00 --> 00:17:02
molecules -- you can have an
enzyme that's actually made

286
00:17:02 --> 00:17:05
of RNA, but most are
protein molecules.

287
00:17:05 --> 00:17:10
And they're typically about
20,000 grams per mole or more,

288
00:17:10 --> 00:17:14
and they're capable of carrying
out specific reactions.

289
00:17:14 --> 00:17:18
And so, they're made up of
amino acids, and just to take a

290
00:17:18 --> 00:17:21
quick look at that, an amino
acid has an amino group and it

291
00:17:21 --> 00:17:24
has a carboxyl group, and it
has what's called an alpha

292
00:17:24 --> 00:17:30
carbon that has a side chain on
it, which is abbreviated r, and

293
00:17:30 --> 00:17:32
there are 20 different
types of r.

294
00:17:32 --> 00:17:35
The simplest is just a
hydrogen, you could also

295
00:17:35 --> 00:17:37
have a hydroxide, etc.
 

296
00:17:37 --> 00:17:40
And so, this makes up the
alphabet of proteins, there are

297
00:17:40 --> 00:17:43
20 different ones of these that
get connected via

298
00:17:43 --> 00:17:45
a peptide bond.
 

299
00:17:45 --> 00:17:48
So at the end of this amino
acid you'd stick on the amino

300
00:17:48 --> 00:17:52
group of another amino acid
and form this peptide bond.

301
00:17:52 --> 00:17:55
And then you put together
hundreds and hundreds of these

302
00:17:55 --> 00:17:58
to form an enzyme complex.
 

303
00:17:58 --> 00:18:03
And so, the long chain of amino
acids folds up and forms

304
00:18:03 --> 00:18:05
a compact structure.
 

305
00:18:05 --> 00:18:10
So, in this particular picture,
there are about 200 amino acids

306
00:18:10 --> 00:18:14
in each of these colored units,
so this is a tetramer, so there

307
00:18:14 --> 00:18:19
are four -- there's green,
red, yellow and blue.

308
00:18:19 --> 00:18:21
And so, this is what's
called a ribbon diagram.

309
00:18:21 --> 00:18:24
So, these ribbons, this
is an alpha helix -- the

310
00:18:24 --> 00:18:27
beta strands are long.
 

311
00:18:27 --> 00:18:30
It traces out the position
of the alpha carbons.

312
00:18:30 --> 00:18:34
And overall, this structure
is about 90 angstroms by 70

313
00:18:34 --> 00:18:36
angstroms by 50 angstroms.
 

314
00:18:36 --> 00:18:40
Of course, 1 angstroms is 1
times 10 the minus 10 meters.

315
00:18:40 --> 00:18:42
So these are fairly small.
 

316
00:18:42 --> 00:18:46
These protein molecules are,
of course, in your body.

317
00:18:46 --> 00:18:52
And this particular one is
an enzyme that makes an

318
00:18:52 --> 00:18:55
antibiotic, and that antibiotic
is fosfomycin, shown here.

319
00:18:55 --> 00:19:02
And so, fosfomycin is used
in antibiotic combination

320
00:19:02 --> 00:19:06
therapies to treat staph
infections and other

321
00:19:06 --> 00:19:09
kinds of very difficult
infections to treat.

322
00:19:09 --> 00:19:13
And so, I always talk
about the things that I'm

323
00:19:13 --> 00:19:15
most concerned about.
 

324
00:19:15 --> 00:19:18
There are a lot of things
that are big threats that I

325
00:19:18 --> 00:19:20
don't worry too much about.
 

326
00:19:20 --> 00:19:22
Antibiotic resistance is
something I actually

327
00:19:22 --> 00:19:23
worry a lot about.
 

328
00:19:23 --> 00:19:25
I guess I go to too many
meetings were they

329
00:19:25 --> 00:19:26
talk about problems.
 

330
00:19:26 --> 00:19:32
But the rate at which different
kinds of bacteria are becoming

331
00:19:32 --> 00:19:36
resistant to antibiotics
seems to be increasing.

332
00:19:36 --> 00:19:40
So it used to take a lot longer
before a resistance would

333
00:19:40 --> 00:19:42
appear than it does now.
 

334
00:19:42 --> 00:19:46
And there really haven't been,
I think since about 1980s or

335
00:19:46 --> 00:19:48
so, really new antibiotics.
 

336
00:19:48 --> 00:19:53
So, we're still using the same
antibiotics that we have been,

337
00:19:53 --> 00:19:57
which causes more things to
become immune or resistant to

338
00:19:57 --> 00:20:01
those antibiotics, and I think
this is really dangerous.

339
00:20:01 --> 00:20:04
And there's not enough money
in it for the pharmaceutical

340
00:20:04 --> 00:20:06
industry to really
go after this.

341
00:20:06 --> 00:20:11
And it's not just a problem for
biological warfare, although

342
00:20:11 --> 00:20:16
that is a possibility, but also
in hospitals, you go in for

343
00:20:16 --> 00:20:19
some kind of surgery, you have
to worry about the fact that

344
00:20:19 --> 00:20:22
even if the surgery goes great,
you might get an infection that

345
00:20:22 --> 00:20:25
could really compromise your
health in the hospital.

346
00:20:25 --> 00:20:29
And so, whether you have a
heart problem, if you have

347
00:20:29 --> 00:20:34
cancer, you become immune
compromised, there's a lot, a

348
00:20:34 --> 00:20:38
lot of cases where people end
up not dying of cancer

349
00:20:38 --> 00:20:43
directly, they end up dying of
the bacterial infection

350
00:20:43 --> 00:20:45
that can't be treated.
 

351
00:20:45 --> 00:20:47
So this is really
a huge problem.

352
00:20:47 --> 00:20:49
So I always like to let
you know all the possible

353
00:20:49 --> 00:20:52
problems that you can
solve in your future.

354
00:20:52 --> 00:20:55
This is one that I think is
particularly important, and I

355
00:20:55 --> 00:20:58
hope some of you will focus on
this, because we really need

356
00:20:58 --> 00:21:01
different kinds of antibiotics,
or we need to change the way we

357
00:21:01 --> 00:21:05
do medicine in this country so
that resistance doesn't become

358
00:21:05 --> 00:21:08
as much of a problem
as it has been.

359
00:21:08 --> 00:21:13
All right, so that enzyme made
an antibiotic, so we like it,

360
00:21:13 --> 00:21:16
and let's talk about
how that works.

361
00:21:16 --> 00:21:19
How that particular series
of amino acids folds up

362
00:21:19 --> 00:21:21
to do that reaction.
 

363
00:21:21 --> 00:21:24
So now we have some new
nomenclature, and sometimes

364
00:21:24 --> 00:21:27
when people get into the
biochemistry world they get

365
00:21:27 --> 00:21:28
scared because there are
all these words that they

366
00:21:28 --> 00:21:30
don't know what they mean.
 

367
00:21:30 --> 00:21:33
So most of them are not -- they
are things that you can relate

368
00:21:33 --> 00:21:35
back to something
you already know.

369
00:21:35 --> 00:21:38
So, we've been talking about
reactants, and when you have a

370
00:21:38 --> 00:21:42
reactant with an enzyme, it's
usually called a substrate.

371
00:21:42 --> 00:21:45
So this is just another name
for a reactant molecule.

372
00:21:45 --> 00:21:48
And then substrates tend to
bind in what we call the active

373
00:21:48 --> 00:21:51
site of the enzyme, which is
the part of the enzyme that's

374
00:21:51 --> 00:21:52
going to do the chemistry.
 

375
00:21:52 --> 00:21:55
So those are two terms
that you'll hear about

376
00:21:55 --> 00:21:57
in biochemistry.
 

377
00:21:57 --> 00:22:01
All right, so we have an
enzyme, we'll call it e, it

378
00:22:01 --> 00:22:04
binds a substrate, we'll call
that s, and then it forms an

379
00:22:04 --> 00:22:09
enzyme substrate complex, which
we'll call an e s complex,

380
00:22:09 --> 00:22:10
for enzyme substrate.
 

381
00:22:10 --> 00:22:14
And then that enzyme substrate
complex will go to enzyme and

382
00:22:14 --> 00:22:16
product, which we'll call p.
 

383
00:22:16 --> 00:22:20
And if you look in the
state-of-the-art biochemistry

384
00:22:20 --> 00:22:22
books, these are the
abbreviations you'll

385
00:22:22 --> 00:22:23
see in there as well.
 

386
00:22:23 --> 00:22:28
So, this pains me greatly to
show this cartoon, because I

387
00:22:28 --> 00:22:30
spend my career determining
3-dimensional structures of

388
00:22:30 --> 00:22:33
proteins, and so to describe
it as a little squiggly

389
00:22:33 --> 00:22:35
is painful for me.
 

390
00:22:35 --> 00:22:36
But nonetheless, there you go.
 

391
00:22:36 --> 00:22:40
Also, the substrate is almost
about as big as the enzyme.

392
00:22:40 --> 00:22:42
That is also usually not true.
 

393
00:22:42 --> 00:22:45
But nonetheless, here's
a little cartoon.

394
00:22:45 --> 00:22:48
Here's our substrate binding
to our enzyme, it's

395
00:22:48 --> 00:22:50
forming an e s complex.
 

396
00:22:50 --> 00:22:53
And then the enzyme is going to
move the ears of the substrate

397
00:22:53 --> 00:22:58
around to form product, and
now product is released.

398
00:22:58 --> 00:23:02
So, this is actually
pretty simple in terms

399
00:23:02 --> 00:23:05
of writing a mechanism.
 

400
00:23:05 --> 00:23:08
And so, what we can do is write
a mechanism the way that we

401
00:23:08 --> 00:23:11
have been writing a mechanism
so far in this class.

402
00:23:11 --> 00:23:14
And so we're going to go
through this, we're going to

403
00:23:14 --> 00:23:17
derive expression mostly to
show you that all the things

404
00:23:17 --> 00:23:20
you've been learning are
related to chemistry, they're

405
00:23:20 --> 00:23:22
also related to biochemistry.
 

406
00:23:22 --> 00:23:26
So, you already know a lot of
biochemistry from just studying

407
00:23:26 --> 00:23:28
freshman chemistry in 511-1.
 

408
00:23:28 --> 00:23:31
All right, so we have 2
steps in our mechanism.

409
00:23:31 --> 00:23:34
We have enzyme binding
substrate to form an

410
00:23:34 --> 00:23:38
intermediate enzyme substrate
complex, which then goes on

411
00:23:38 --> 00:23:42
to form enzyme plus
product in step 2.

412
00:23:42 --> 00:23:44
So the first step is
reversible, the second

413
00:23:44 --> 00:23:47
step is not as drawn.
 

414
00:23:47 --> 00:23:49
All right, so now we can come
up with the rates for each of

415
00:23:49 --> 00:23:54
the individual steps in this
overall mechanism, and since

416
00:23:54 --> 00:23:57
they are elementary reactions
or steps in an overall

417
00:23:57 --> 00:24:00
mechanism, we can write
the rate laws directly

418
00:24:00 --> 00:24:02
from what we observe.
 

419
00:24:02 --> 00:24:04
So for the forward direction,
we're going to have

420
00:24:04 --> 00:24:07
what rate constant?
 

421
00:24:07 --> 00:24:11
K 1 times the
concentration of what?

422
00:24:11 --> 00:24:13
And?
 

423
00:24:13 --> 00:24:14
Yeah.
 

424
00:24:14 --> 00:24:15
So there we go.
 

425
00:24:15 --> 00:24:17
We have k 1 times the
concentration of e and

426
00:24:17 --> 00:24:19
the concentration of s.
 

427
00:24:19 --> 00:24:21
See, you already knew
how to do biochemistry.

428
00:24:21 --> 00:24:26
All right, so now at the rate
of the reverse direction is

429
00:24:26 --> 00:24:29
-- what's our rate constant?
 

430
00:24:29 --> 00:24:32
K minus 1 times e s.
 

431
00:24:32 --> 00:24:36
And then for step 2, we
have what rate constant?

432
00:24:36 --> 00:24:41
K 2 times e s.
 

433
00:24:41 --> 00:24:44
All right, so now we can
talk about the rate

434
00:24:44 --> 00:24:46
formation of product.
 

435
00:24:46 --> 00:24:51
And so you'll see this
expressed as d concentration of

436
00:24:51 --> 00:24:56
p d t, so the change in product
that's being formed and that's

437
00:24:56 --> 00:25:01
going to be equal to the second
step here, k 2 times e s.

438
00:25:01 --> 00:25:05
But, as has been the case
before, e s is an intermediate,

439
00:25:05 --> 00:25:09
and we need to solve our rate
laws, our rate expressions,

440
00:25:09 --> 00:25:13
in terms of reactants or
products and rate constants.

441
00:25:13 --> 00:25:18
So we need to solve
for the intermediate.

442
00:25:18 --> 00:25:22
All right, so let's think about
solving for the intermediate.

443
00:25:22 --> 00:26:27
And why don't you tell
me how to do that.

444
00:26:27 --> 00:26:42
OK, let's just take
10 more seconds.

445
00:26:42 --> 00:26:43
Very good.
 

446
00:26:43 --> 00:26:49
All right, so let's just take a
look at why that is the case.

447
00:26:49 --> 00:26:55
So, when we solve for this,
it's going to be equal to the

448
00:26:55 --> 00:26:59
formation of the intermediate,
which happens in the first step

449
00:26:59 --> 00:27:01
with this rate that you
told me, k 1 times the

450
00:27:01 --> 00:27:03
concentration of e s.
 

451
00:27:03 --> 00:27:06
And then we have the
decomposition in the reverse

452
00:27:06 --> 00:27:11
of step one, so that's
minus k minus 1 e s.

453
00:27:11 --> 00:27:14
And then we also have
the consumption of the

454
00:27:14 --> 00:27:17
intermediate, which is -- so
we have minus this step,

455
00:27:17 --> 00:27:20
which is k 2 times e s.
 

456
00:27:20 --> 00:27:23
So again, formation
minus decomposition

457
00:27:23 --> 00:27:26
minus consumption.
 

458
00:27:26 --> 00:27:30
And now, we can use the
steady state approximation.

459
00:27:30 --> 00:27:32
So the steady state
approximation applies in

460
00:27:32 --> 00:27:37
biochemistry just as well as in
all of your chemistry problems

461
00:27:37 --> 00:27:39
that you've done
in this course.

462
00:27:39 --> 00:27:43
And so, the steady state
approximation allows us to set

463
00:27:43 --> 00:27:46
that whole term equal to zero.
 

464
00:27:46 --> 00:27:51
So it says that the net rate of
intermediate formation and

465
00:27:51 --> 00:27:56
decomposition and consumption
is 0, or you can express it as

466
00:27:56 --> 00:28:00
the rate of formation of the
intermediate equals the rates

467
00:28:00 --> 00:28:03
of decomposition and
consumption -- those

468
00:28:03 --> 00:28:05
are equivalent.
 

469
00:28:05 --> 00:28:07
So we can set all of
this equal to zero.

470
00:28:07 --> 00:28:13
So again, the same as
what we've done before.

471
00:28:13 --> 00:28:15
All right, so now we're going
to have a slight change of what

472
00:28:15 --> 00:28:19
we've done before, and this has
to do with the practical

473
00:28:19 --> 00:28:20
consideration.
 

474
00:28:20 --> 00:28:26
So you can solve for these in
terms of reactants and products

475
00:28:26 --> 00:28:31
and rate constants, but it's
actually easier to solve for e

476
00:28:31 --> 00:28:37
s in terms of your total enzyme
rather than your free enzyme.

477
00:28:37 --> 00:28:41
So what we've had before is our
free enzyme, but we often don't

478
00:28:41 --> 00:28:43
know how much enzyme is free,
and by that we mean not

479
00:28:43 --> 00:28:46
bound to the substrate.
 

480
00:28:46 --> 00:28:49
And so, we know how much total
enzyme we put in, but we might

481
00:28:49 --> 00:28:52
not know how much of
that is unbound.

482
00:28:52 --> 00:28:55
So it's actually easier for
the experimentalist to

483
00:28:55 --> 00:28:58
solve for things in
terms of total enzyme.

484
00:28:58 --> 00:29:03
And so what we're going to do
then is we're going to replace

485
00:29:03 --> 00:29:07
our free enzyme term with the
following, total enzyme minus

486
00:29:07 --> 00:29:11
bound, and total enzyme minus
the bound enzyme is

487
00:29:11 --> 00:29:12
the free enzyme.
 

488
00:29:12 --> 00:29:16
So we're going to do this
change that makes it easier

489
00:29:16 --> 00:29:19
for the experimentalist.
 

490
00:29:19 --> 00:29:22
So here's the term we had
before, but now we want to

491
00:29:22 --> 00:29:28
replace this term of e
with e to 0 minus e s.

492
00:29:28 --> 00:29:30
So we're going to put that,
here's the term e up here,

493
00:29:30 --> 00:29:34
so we're going to replace
that with e 0 minus e s.

494
00:29:34 --> 00:29:37
And then we're going to
multiply that out, so we get k

495
00:29:37 --> 00:29:44
1, e 0, s minus k 1, e s, and
then the concentration of

496
00:29:44 --> 00:29:46
substrate here, and the
rest of it is the same.

497
00:29:46 --> 00:29:50
So we got rid of our term e.
 

498
00:29:50 --> 00:29:55
So now we can solve for e s.
 

499
00:29:55 --> 00:29:58
So this is what we just had,
and so we're going to rearrange

500
00:29:58 --> 00:30:01
so the e s terms are on one
side, so we have an e s

501
00:30:01 --> 00:30:03
term here, here, and here.
 

502
00:30:03 --> 00:30:05
So all that is going to be on
one side, and then this other

503
00:30:05 --> 00:30:08
term will be on the other
side of the equation.

504
00:30:08 --> 00:30:12
So now we have moved all the e
s terms over here, so we've got

505
00:30:12 --> 00:30:14
rid of the negative numbers,
we've added them all to the

506
00:30:14 --> 00:30:17
other side, and then on
this side we just have

507
00:30:17 --> 00:30:19
this k 1 term left.
 

508
00:30:19 --> 00:30:22
Now we're going to pull
out the e s terms.

509
00:30:22 --> 00:30:24
So, we'll solve for e s.
 

510
00:30:24 --> 00:30:28
We'll pull that out, that
leaves us with k 1 times

511
00:30:28 --> 00:30:32
the concentration of s,
k minus 1, and then k 2.

512
00:30:32 --> 00:30:36
And now we're going to take
this and divide by that term in

513
00:30:36 --> 00:30:41
parentheses, and so now we've
solved for e s in terms of

514
00:30:41 --> 00:30:46
total enzyme substrate
and our rate constants.

515
00:30:46 --> 00:30:47
All right, now we're going
to do another thing

516
00:30:47 --> 00:30:49
that's a bit different.
 

517
00:30:49 --> 00:30:53
We're going to introduce a term
in biochemistry, which is k m,

518
00:30:53 --> 00:30:57
also known as the
Michaelis-Menten constant, and

519
00:30:57 --> 00:31:01
so k m is equal to the rate
constant for the

520
00:31:01 --> 00:31:08
forward/reverse direction, k
minus 1 plus k 2 over k 1.

521
00:31:08 --> 00:31:14
So we're going to now try to
use this in our expression.

522
00:31:14 --> 00:31:20
So we're going to put this term
in there, and so to have this

523
00:31:20 --> 00:31:25
term of k m in there, we need
to have this divided by k 1.

524
00:31:25 --> 00:31:29
So we can do that, it's OK, as
long as we divide everything by

525
00:31:29 --> 00:31:32
k 1, so we're going to divide
the top by k 1, and this

526
00:31:32 --> 00:31:35
by k 1, and that by k 1.
 

527
00:31:35 --> 00:31:41
So now, we divide all by k 1,
and so we have this top with k

528
00:31:41 --> 00:31:44
1, this term with k 1, and this
with k 1, and that's

529
00:31:44 --> 00:31:46
our k m value.
 

530
00:31:46 --> 00:31:49
But now we can simplify this,
we've got a lot of k 1's here,

531
00:31:49 --> 00:31:53
and so if we simplify this, we
can cross out those

532
00:31:53 --> 00:31:56
k 1's over there.
 

533
00:31:56 --> 00:32:00
And we can also get rid of
these k 1's over here.

534
00:32:00 --> 00:32:03
And that's going to leave us
with a much simpler expression.

535
00:32:03 --> 00:32:07
So that's going to leave
us with the total enzyme

536
00:32:07 --> 00:32:11
times substrate over
substrate plus k m.

537
00:32:11 --> 00:32:13
And that looks a whole lot
better than that other

538
00:32:13 --> 00:32:21
term that we had before.
 

539
00:32:21 --> 00:32:25
OK, so we can now take this and
substitute it back into the

540
00:32:25 --> 00:32:29
expression we had earlier.
 

541
00:32:29 --> 00:32:34
So here we had the rate of
product formation, k 2 times

542
00:32:34 --> 00:32:37
this intermediate, we solved
for the intermediate

543
00:32:37 --> 00:32:41
using total enzyme and
using this k m term.

544
00:32:41 --> 00:32:45
And now we just put all
of this times k 2.

545
00:32:45 --> 00:32:48
And if you put all of that
times k 2, you have this

546
00:32:48 --> 00:32:52
expression, which is the
Michaelis-Menten equation.

547
00:32:52 --> 00:32:56
So the only difference of what
you did before was that you

548
00:32:56 --> 00:33:00
solved in terms of total
enzyme, and also, we

549
00:33:00 --> 00:33:03
have this new k m term.
 

550
00:33:03 --> 00:33:06
And so now we have an equation
that's used in a lot of

551
00:33:06 --> 00:33:12
biochemistry research to
think about enzyme kinetics.

552
00:33:12 --> 00:33:15
So let's think about enzyme
kinetics for a minute.

553
00:33:15 --> 00:33:18
This is what a plot often looks
like -- we are looking at the

554
00:33:18 --> 00:33:22
product formed by an enzyme
versus the concentration

555
00:33:22 --> 00:33:23
of substrate.
 

556
00:33:23 --> 00:33:24
And it often goes up.
 

557
00:33:24 --> 00:33:28
It's pretty steep, and then
it starts to level off.

558
00:33:28 --> 00:33:31
So let's think about
what's happening here.

559
00:33:31 --> 00:33:35
So if you have low substrate,
so that's way down here, not

560
00:33:35 --> 00:33:39
much substrate is available,
adding more substrate

561
00:33:39 --> 00:33:42
will increase this rate
significantly, you'll form a

562
00:33:42 --> 00:33:45
lot more product, it increases
the rate of product formation.

563
00:33:45 --> 00:33:48
Because a lot of the enzyme
is free and can react

564
00:33:48 --> 00:33:49
with substrate.
 

565
00:33:49 --> 00:33:53
So it goes up, but then the
rate starts to level off.

566
00:33:53 --> 00:33:58
So when you got to higher
substrate concentrations,

567
00:33:58 --> 00:34:02
adding more substrate does not
affect the rate much, the

568
00:34:02 --> 00:34:03
rate is leveling off.
 

569
00:34:03 --> 00:34:06
And we say that the
enzyme is saturated.

570
00:34:06 --> 00:34:10
All the enzyme that you have in
there already has substrate

571
00:34:10 --> 00:34:12
going on, it's already
doing the chemistry.

572
00:34:12 --> 00:34:15
So if you're throwing more at
it, the enzyme can't bind that

573
00:34:15 --> 00:34:19
substrate, it's busy with a
different substrate molecule.

574
00:34:19 --> 00:34:22
So all the active sites in
the enzyme are full, and

575
00:34:22 --> 00:34:24
so not much happens.
 

576
00:34:24 --> 00:34:28
So this kind of graph
is what you often see

577
00:34:28 --> 00:34:32
in enzyme kinetics.
 

578
00:34:32 --> 00:34:34
Now let's think about
that in terms of our

579
00:34:34 --> 00:34:34
Michaelis-Menten equation.
 

580
00:34:34 --> 00:34:40
So let's think about conditions
when there's a lot of

581
00:34:40 --> 00:34:44
substrate, when substrate is
much greater than k m.

582
00:34:44 --> 00:34:48
So here we have substrate and
k m on the bottom of our

583
00:34:48 --> 00:34:52
equation, and what's going to
happen if this term is much,

584
00:34:52 --> 00:34:56
much bigger than this k m term?
 

585
00:34:56 --> 00:35:00
What happens to the k m term?
 

586
00:35:00 --> 00:35:01
It goes away.
 

587
00:35:01 --> 00:35:04
It's really small compared
to this, it's kind

588
00:35:04 --> 00:35:06
of insignificant.
 

589
00:35:06 --> 00:35:10
So, if that happens, then you
can cancel substrate as well.

590
00:35:10 --> 00:35:13
And so, that means that under
conditions where substrate is

591
00:35:13 --> 00:35:18
much greater than k m, the rate
is a much simpler term, it's

592
00:35:18 --> 00:35:22
just equal to k 2 times
your total enzyme.

593
00:35:22 --> 00:35:26
And so this has a name, this
is called Vmax or the maximum

594
00:35:26 --> 00:35:29
velocity of the reaction.
 

595
00:35:29 --> 00:35:32
So, under these conditions,
when the substrate is much

596
00:35:32 --> 00:35:36
greater than that k m value,
this expression simplifies and

597
00:35:36 --> 00:35:40
you get just k 2, your rate
constant, times your total

598
00:35:40 --> 00:35:44
enzyme, and that'll give you
the maximum velocity

599
00:35:44 --> 00:35:47
of the reaction.
 

600
00:35:47 --> 00:35:49
And so, that's just
written again here.

601
00:35:49 --> 00:35:53
Vmax equals k 2 times total
enzyme, and that equation

602
00:35:53 --> 00:35:55
will be given to you
on an equation sheet.

603
00:35:55 --> 00:35:56
So what's happening?
 

604
00:35:56 --> 00:35:58
What's happening is
that you're up here.

605
00:35:58 --> 00:36:04
So when substrate concentration
is much greater than k m, then

606
00:36:04 --> 00:36:06
you're in these conditions,
and you're at some

607
00:36:06 --> 00:36:07
maximum velocity.
 

608
00:36:07 --> 00:36:10
So the velocity will only go,
the rate of the reaction will

609
00:36:10 --> 00:36:14
only go so fast, it will
saturate, it'll level off up

610
00:36:14 --> 00:36:17
here, and so you can calculate
that maximum rate

611
00:36:17 --> 00:36:20
of that reaction.
 

612
00:36:20 --> 00:36:24
Now let's consider what
happens when your substrate

613
00:36:24 --> 00:36:27
concentration equals your k m.
 

614
00:36:27 --> 00:36:32
So down here, if k m is
equal to substrate, then

615
00:36:32 --> 00:36:36
we're going to have two
substrates down here.

616
00:36:36 --> 00:36:39
And so, we can write this, if
they're equal, we can write

617
00:36:39 --> 00:36:44
this as substrate plus
substrate, and then we

618
00:36:44 --> 00:36:46
can do some canceling.
 

619
00:36:46 --> 00:36:50
So this will be equal to 2
substrates and then we can

620
00:36:50 --> 00:36:54
cancel that out, and so we get
the rate of product formation

621
00:36:54 --> 00:36:58
under conditions where
substrate equals k m of

622
00:36:58 --> 00:37:04
1/2 k 2 times the total
enzyme concentration.

623
00:37:04 --> 00:37:07
And this is referred to
the half maximal rate.

624
00:37:07 --> 00:37:13
Remember, the maximal rate was
k 2 times this e knot, and

625
00:37:13 --> 00:37:18
so half of that is half
the maximal rate here.

626
00:37:18 --> 00:37:23
So, the definition of k m
is the concentration of

627
00:37:23 --> 00:37:28
substrate for which the
rate is half maximal.

628
00:37:28 --> 00:37:32
So if your rate is half of the
maximum rate, that substrate

629
00:37:32 --> 00:37:36
concentration that gives you
half the maximum rate,

630
00:37:36 --> 00:37:38
is the value for k m.
 

631
00:37:38 --> 00:37:44
Substrate concentration equals
k m at the half maximal rate.

632
00:37:44 --> 00:37:45
So let's just look
at what that meant.

633
00:37:45 --> 00:37:52
So if this is Vmax up here,
half of Vmax is here, half of

634
00:37:52 --> 00:37:56
that value, and the substrate
concentration at half

635
00:37:56 --> 00:37:59
Vmax is equal to k m.
 

636
00:37:59 --> 00:38:03
So you can write those
in on your diagram.

637
00:38:03 --> 00:38:07
Vmax is this velocity up here,
half of that, when you're at

638
00:38:07 --> 00:38:12
half of the maximal rate, k m
equals the substrate

639
00:38:12 --> 00:38:14
concentration.
 

640
00:38:14 --> 00:38:18
And there will be problems that
you will work in your book very

641
00:38:18 --> 00:38:22
shortly, and often, the
problems just have to do,

642
00:38:22 --> 00:38:25
they'll give you the
information in words and the

643
00:38:25 --> 00:38:27
calculations can often
be pretty simple.

644
00:38:27 --> 00:38:31
Sometimes it'll say, figure
out what the k m for

645
00:38:31 --> 00:38:32
this reaction is.
 

646
00:38:32 --> 00:38:34
At this substrate
concentration, the

647
00:38:34 --> 00:38:35
rate is half maximal.
 

648
00:38:35 --> 00:38:39
Well, at that substrate
concentration, that's the k m.

649
00:38:39 --> 00:38:42
So, a lot of the problems are
sort of word problems, they

650
00:38:42 --> 00:38:44
give you the information and
you need to know what

651
00:38:44 --> 00:38:46
the definitions are.
 

652
00:38:46 --> 00:38:48
But let's try an example.
 

653
00:38:48 --> 00:38:54
So here in this example, we've
talked about buffering in the

654
00:38:54 --> 00:39:00
blood, so the conversion of
your ingredients that make your

655
00:39:00 --> 00:39:05
buffering agent in the blood,
that can be catalyzed by

656
00:39:05 --> 00:39:08
an enzyme called
carbonicanhydrase, and the

657
00:39:08 --> 00:39:13
following Michaelis-Menten
constants are known, a k m is

658
00:39:13 --> 00:39:18
known, and a k 2 is known, and
if you're doing experiment and

659
00:39:18 --> 00:39:22
you have a total concentration
of your enzyme of 5 times 10 to

660
00:39:22 --> 00:39:26
the minus 6 molar, then you
should be able to figure out

661
00:39:26 --> 00:39:31
what the maximum rate of the
reaction would be.

662
00:39:31 --> 00:39:33
So, why don't you go ahead
and tell me what the

663
00:39:33 --> 00:40:34
maximum rate would be.
 

664
00:40:34 --> 00:40:49
OK, let's just take
10 more seconds.

665
00:40:49 --> 00:40:49
Very good.
 

666
00:40:49 --> 00:40:51
Everyone's doing
very good today.

667
00:40:51 --> 00:40:57
All right, so all you have to
do, you have remember Vmax

668
00:40:57 --> 00:41:01
equals your total enzyme
concentration times your k 2.

669
00:41:01 --> 00:41:05
And pretty much no one,
hardly anyone was fooled

670
00:41:05 --> 00:41:07
by k m value there.
 

671
00:41:07 --> 00:41:11
All right, very good.
 

672
00:41:11 --> 00:41:16
So there are extra problems
on enzyme kinetics posted

673
00:41:16 --> 00:41:18
on the extra problems
posted on the Web.

674
00:41:18 --> 00:41:22
So there's a few there, so you
can see the type of problems,

675
00:41:22 --> 00:41:24
again, they're like that,
they're pretty simple.

676
00:41:24 --> 00:41:28
If you remember the definition
of k m, and you'll be given the

677
00:41:28 --> 00:41:31
equation for Vmax, you
should be able to handle

678
00:41:31 --> 00:41:35
the enzyme/kinetics
problems pretty well.

679
00:41:35 --> 00:41:39
Often, also I'll ask questions
like explain why at high

680
00:41:39 --> 00:41:44
substrate concentrations, the
rate does not increase very

681
00:41:44 --> 00:41:48
much, or why the graph levels
off, or I might ask you to draw

682
00:41:48 --> 00:41:53
the plot and tell me about low
substrate concentrations,

683
00:41:53 --> 00:41:56
what's true there, and high
substrate concentrations,

684
00:41:56 --> 00:41:56
what's true.
 

685
00:41:56 --> 00:41:58
So those are the types of
questions you're going to get

686
00:41:58 --> 00:42:03
on enzyme kinetics, they're
actually pretty simple.

687
00:42:03 --> 00:42:05
All right, so let's just
talk briefly about

688
00:42:05 --> 00:42:07
enzyme inhibition.
 

689
00:42:07 --> 00:42:11
So the opposite of catalysis --
instead of binding a substrate,

690
00:42:11 --> 00:42:13
you'll bind an inhibitor.
 

691
00:42:13 --> 00:42:19
So often, these are
actually pretty simple.

692
00:42:19 --> 00:42:22
An inhibitor sometimes will
look a lot like a substrate or

693
00:42:22 --> 00:42:26
like a transition complex, and
it'll blind to the enzyme.

694
00:42:26 --> 00:42:29
And when you have that
inhibitor stuck in the active

695
00:42:29 --> 00:42:33
site, substrate physically
can't bind, so it occupies the

696
00:42:33 --> 00:42:36
place that substrate goes,
substrate will come in but

697
00:42:36 --> 00:42:38
it can't bind anywhere.
 

698
00:42:38 --> 00:42:42
So this is actually the
mechanism by which a number

699
00:42:42 --> 00:42:44
of pharmaceuticals work.
 

700
00:42:44 --> 00:42:49
So, one thing that people who
were designing enzyme

701
00:42:49 --> 00:42:56
inhibitors think about is the
fact that enzymes do tend to

702
00:42:56 --> 00:43:00
stabilize a transition
state in the reaction.

703
00:43:00 --> 00:43:05
So if you make an inhibitor
that resembles a transition

704
00:43:05 --> 00:43:10
state, it should bind to the
enzyme more tightly than

705
00:43:10 --> 00:43:14
either the reactants, the
substrates, or the products.

706
00:43:14 --> 00:43:18
So, a lot of the pharmaceutical
industry likes to try to figure

707
00:43:18 --> 00:43:22
out what the transition state
might look like, and then try

708
00:43:22 --> 00:43:26
to make a molecule that looks
like that transition state that

709
00:43:26 --> 00:43:29
hopefully will blind to the
enzyme active site and prevent

710
00:43:29 --> 00:43:35
the enzyme from doing what
it's supposed to do.

711
00:43:35 --> 00:43:38
So, just to kind of look back
at this figure for a minute

712
00:43:38 --> 00:43:41
that you had earlier in your
notes, so you have the

713
00:43:41 --> 00:43:46
transition state is often
stabilized by a catalyst, and

714
00:43:46 --> 00:43:50
so an enzyme will also
stabilize a transition state.

715
00:43:50 --> 00:43:53
So if you make your drug look
like a transition state, it

716
00:43:53 --> 00:43:56
will hopefully bind
very tightly.

717
00:43:56 --> 00:44:02
And so this is one of the sort
of principles that's behind a

718
00:44:02 --> 00:44:05
lot of the pharmaceuticals that
have made to treat

719
00:44:05 --> 00:44:07
HIV infections.
 

720
00:44:07 --> 00:44:11
So I mentioned last week we
had world AIDS day, that

721
00:44:11 --> 00:44:14
understanding kinetics was
actually very important

722
00:44:14 --> 00:44:16
in HIV research.
 

723
00:44:16 --> 00:44:19
And so, many of the
pharmaceuticals that are given

724
00:44:19 --> 00:44:23
to HIV patients are what are
called protease inhibitors.

725
00:44:23 --> 00:44:27
So they inhibit enzymes that
are called proteases, and if

726
00:44:27 --> 00:44:31
you have ase at the end of the
name that means it's an enzyme,

727
00:44:31 --> 00:44:34
and so protease means that
it's an enzyme that

728
00:44:34 --> 00:44:35
cleaves proteins.
 

729
00:44:35 --> 00:44:37
It's a protein ase.
 

730
00:44:37 --> 00:44:40
And so, how do these
enzymes work.

731
00:44:40 --> 00:44:43
Well, they cleave other
proteins, they cleave peptide

732
00:44:43 --> 00:44:46
bonds, and so you often have
some kind of either activated

733
00:44:46 --> 00:44:51
water or other hydroxide
molecule that will attack here

734
00:44:51 --> 00:44:56
the carbonyl of a peptide bond,
and it forms a tetrahedral

735
00:44:56 --> 00:44:59
intermediate, which then
collapses and it cleaves

736
00:44:59 --> 00:45:00
that peptide bond.
 

737
00:45:00 --> 00:45:03
So the peptide bond is then
broken, so that's what a

738
00:45:03 --> 00:45:06
protease does, and a
protease inhibitor

739
00:45:06 --> 00:45:08
prevents that cleavage.
 

740
00:45:08 --> 00:45:12
So often, protease inhibitors
look like tetrahedral

741
00:45:12 --> 00:45:15
intermediates, and so they'll
bind to the protease active

742
00:45:15 --> 00:45:18
site and prevent the
chemistry from occurring.

743
00:45:18 --> 00:45:21
So if it's a tetrahedral
intermediate, what kind

744
00:45:21 --> 00:45:24
of angles should some
pharmaceutical company be

745
00:45:24 --> 00:45:26
looking for in its compounds?
 

746
00:45:26 --> 00:45:28
109 .
 

747
00:45:28 --> 00:45:30
5, yes.
 

748
00:45:30 --> 00:45:36
So, molecules with this stable
tetrahedral intermediate

749
00:45:36 --> 00:45:41
somewhere on the molecule
could bind to the active site

750
00:45:41 --> 00:45:43
and prevent a catalysis.
 

751
00:45:43 --> 00:45:46
So, let me just show you one
example of an improved HIV

752
00:45:46 --> 00:45:48
drug, and there it is.
 

753
00:45:48 --> 00:45:54
This is the tetrahedral site
that binds at the active site

754
00:45:54 --> 00:45:58
of that enzyme, and the enzyme
can't cleave this tetrahedral

755
00:45:58 --> 00:46:02
intermediate, and so this just
binds, but the enzyme can't

756
00:46:02 --> 00:46:05
work on it, so it just
sits there and prevents

757
00:46:05 --> 00:46:08
substrate from binding.
 

758
00:46:08 --> 00:46:12
So that's how a lot of
these compounds work.

759
00:46:12 --> 00:46:15
And so, this is just a little
picture of the enzyme active

760
00:46:15 --> 00:46:19
site and there's an inhibitor
bound to the enzyme active

761
00:46:19 --> 00:46:22
site, and so a number of
companies are working on trying

762
00:46:22 --> 00:46:25
to come up with better and
better inhibitors that will sit

763
00:46:25 --> 00:46:28
in the HIV protease
active site.

764
00:46:28 --> 00:46:33
So, knowledgeable of a reaction
mechanism can lead to new

765
00:46:33 --> 00:46:35
therapeutic treatments.
 

766
00:46:35 --> 00:46:39
So, one question with this,
with protease, there are a lot

767
00:46:39 --> 00:46:43
of proteases, not just the ones
involved with HIV, and so one

768
00:46:43 --> 00:46:47
real problem is specificity and
toxicity, so you want to have a

769
00:46:47 --> 00:46:51
drug that inhibits one enzyme
and not all the enzymes

770
00:46:51 --> 00:46:53
in that category.
 

771
00:46:53 --> 00:46:56
So that's a big problem in
the pharmaceutical industry.

772
00:46:56 --> 00:47:02
So, apparently, clicker
results, we actually

773
00:47:02 --> 00:47:07
need to break a tie.
 

774
00:47:07 --> 00:47:11
But we can't do it now.
 

775
00:47:11 --> 00:47:19
OK, so Justin's section, woah!
 

776
00:47:19 --> 00:47:22
So, apparently we're having, we
have the questions ready, but

777
00:47:22 --> 00:47:26
apparently they're not ready to
be used right at the moment.

778
00:47:26 --> 00:47:32
So, we're going to use low
tech here and indicate

779
00:47:32 --> 00:47:36
the results for today.
 

780
00:47:36 --> 00:47:42
And then on Wednesday, last
day of class -- oh, my

781
00:47:42 --> 00:47:46
goodness, so close.
 

782
00:47:46 --> 00:47:57
Recitation 6, you were second.
 

783
00:47:57 --> 00:48:02
All right, so on Wednesday
then, we're going to have

784
00:48:02 --> 00:48:06
the tie breaker, and
review and evaluations.

785
00:48:06 --> 00:48:06