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PROFESSOR: What's an enzyme?
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How does it work?
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Well, it's time to really talk about what an enzyme does.
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And so we're going to meet one particular enzyme.
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And that enzyme--
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section two--
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this enzyme is called triose phosphate isomerase.
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Triose phosphate isomerase, TIM amongst friends.
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OK?
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So we call this enzyme TIM.
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Many people do who work on it just refer to it as TIM.
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Now, we talked about oses, we talked about sugars.
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We said that six carbon sugars were hexoses.
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Five carbon sugars were pentoses.
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Three carbon sugars are trioses.
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So this is going to be a three carbon sugar that has a
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phosphate group on it.
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That's what a triose phosphate is.
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Pretty straightforward.
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Actually, most of this stuff makes sense when you get down to it.
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But this enzyme is going to carry out a transformation on one triose
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phosphate and turn it into another triose phosphate.
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It's going to turn it into an isomer.
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Same atoms, but rearranged differently.
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That's what an isomer is.
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So it's going to take one triose with a phosphate on it and turn it into
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another triose with a phosphate on it.
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Sounds easy.
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Let's take a look.
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So triose--
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here is one triose.
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Remember that I need to have three carbons and--
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here we go.
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I've got a hydroxyl here.
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I've got there.
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And instead of having another hydroxyl here-- remember, sugar had one
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carbonyl, hydroxyl, hydroxyl.
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But here I've now, instead, got my phosphate.
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That is a particular triose with a phosphate on it.
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And this guy goes by the name glyceraldehyde 3-phosphate.
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Because it's on the third carbon that that phosphate is.
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It's glyceraldehyde, and 'cause that's a lot to say, it's just G3P.
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So we've got G3P here.
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All right?
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Now I'm going to give you another triose.
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Let's take this triose here.
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Got to have three carbons.
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And we know we're going to have a phosphate on it, so I put that
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phosphate on.
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How is it different?
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Well, it's different here because I've got my double bond here, and I've got
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a hydroxyl there.
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Whereas here I had my double bond here and hydroxyl here.
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Not a big difference, right?
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All right.
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This guy is called dihydroxyacetone phosphate.
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And I don't care if you know what all those words mean, but
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that's what it's called.
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And I'm not expecting you to know these chemical structures here.
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You're going to know how to name chemical structures, and we're just
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going to call DHAP, dihydroxyacetone phosphate.
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So I have a triose phosphate, and I have another triose phosphate.
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What do I need to do to convert this triose phosphate into this one?
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Oh, by the way, this reaction is going to have to go on in fermentation.
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And when we learn about how fermentation works, this is one of
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those reactions.
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So this is one of the things that Buchner squeezed out of yeast, is an
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enzyme that can carry out this particular transformation.
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So what do I got to do?
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Let's see.
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I'm going to--
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STUDENT: Move the H?
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PROFESSOR: Proton up here.
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The H up here.
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So when I'm moving a hydrogen, I'm just moving a proton, because that's
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all the nucleus--
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I'm going to move the H up here.
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STUDENT: And take an electron down there.
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PROFESSOR: Well, I'm going to actually take an H up here.
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So basically, I'm just going to put the H here and the H here, and then
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I'm going to get the C double bond-- somebody said you've
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got to move two Hs.
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This can't be that hard.
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H's don't weigh very much, right?
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So I'm just going to move these Hs.
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Sounds pretty easy.
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Well.
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And it actually turns out to be chemically pretty
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favorable to do this.
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Chemists can measure that with something called the free energy.
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Whether one structure is energetically more or less favorable
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than another structure.
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So the free energy of G3P and the free energy here of DHAP--
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DHAP is actually more energetically favorable.
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It's a lower energy state.
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It's a more favorable state.
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It's actually lower by--
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we write delta G zero prime, which is a measure of free energy.
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And it's better.
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On its own, if you ask these two molecules, this is an energetically
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more favorable state.
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So why doesn't G3P just become DHAP spontaneously?
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STUDENT: [INAUDIBLE].
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PROFESSOR: Sorry?
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STUDENT: Activation energy.
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PROFESSOR: Activation--
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what's activation energy?
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I mean, we say, because there's an activation barrier.
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There's an activation energy.
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What does it mean to say there's an activation energy?
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STUDENT: You need energy to start the reaction.
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PROFESSOR: I need energy, so I just like light a match?
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[LAUGHTER]
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STUDENT: Wouldn't you need to invest some energy into breaking the bonds in
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G3P so that you can move the hydrogen [INAUDIBLE]?
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PROFESSOR: So why do I have to invest energy?
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People always tell you to start investing, but you know, you're young.
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Why you need to start investing here, all this energy?
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What's the point?
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Yeah?
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STUDENT: You'll get more energy back when the bonds reform another one.
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PROFESSOR: I'll get more energy back.
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That's what they always tell you about why you should invest, because you can
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get more back.
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[LAUGHTER]
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And then the molecule pays some interest rate.
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But what's going on?
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Yeah?
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STUDENT: You need to invest energy so the reaction favors the product.
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PROFESSOR: That actually favors the product right now.
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I gave you a reaction that favors that product.
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It actually would rather be DHAP than G3P.
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It's going in the right direction.
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Better free energy.
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So it's already doing that.
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I don't need any energy.
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Yep?
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STUDENT: So globally, the product has a lower free energy
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state than the reactant--
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PROFESSOR: It does.
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STUDENT: --but locally, the reactant is in a lower free energy state than
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in transition.
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PROFESSOR: Transition.
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Tell me about this transition.
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You're saying that to get from here to there, from one molecule to another
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molecule, how do I get there?
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I have to pass through some intermediate state,
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some transition state.
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In fact, to get from here to there, from here to here, it turns out I have
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to pass through this state.
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Chemically, I'm not going to go into the details of why, but it turns out
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that in order to do this, I need to transition through this guy.
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Let's take a look at what's going on.
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Everything below this line is the same.
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But above this line, while I'm doing some moving around here, this is a
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very different molecule.
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I have this double bond here.
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And this guy goes by the funky name cis-enediol.
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And what it is is this is what's called the transition state.
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So cis-enediol is the transition state, or the intermediate.
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And it is a very unhappy molecule.
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It has very high free energy.
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It is not a happy state.
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In fact, it is there.
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So it turns out that the reason that this reaction is not going forward is
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not that it wouldn't like to be DHAP.
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It would love to be DHAP.
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You appreciate, I'm anthropomorphizing when I speak about the desires of
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relatively small molecules, right?
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But nonetheless, it is energetically more favorable to be DHAP.
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But to get from here to there, you have to climb a mountain.
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You have to go through an intermediate molecular state, which is
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extraordinarily unfavorable.
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The chance of this happening on its own is roughly nil.
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Because this is something like 26 kilocalories per mole, which is a lot
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of energy needed.
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Very rare that by chance the molecules are just going to
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happen to go do that.
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And the truth is, it's actually worse than that.
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In this state, not only is this a high energy state, but rather than going
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from here to there, this molecule is so unhappy that its phosphate will
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usually break off.
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Especially in the presence of water.
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So the chance of going from here to here, very, very low.
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And then the chance of managing to keep going without losing the
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phosphate, forget it.
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This is just not going to happen on its own.
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You need to help it.
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That is what an enzyme does.
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Turns out you don't have to invest any energy at all.
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No energy is needed to make this happen.
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I didn't have to spend any energy.
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I don't have to invest any energy, and I don't have to get back any energy.
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None of that is needed.
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Because in fact, it's an energetically favorable reaction.
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It just has to go through some intermediate state.
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And we have to gently help it over the mountain.
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Now that we've finished this segment, test yourself with this question.
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