#20 Biochemistry Metabolic Controls/Energy Lecture for Kevin Ahern's BB 450/550

[students groaning]
Happy Friday.
I will schedule a review session,
as I have done previously for the first exam.
I will announce that next week sometime.
I would guess it would likely be on Tuesday evening.
With respect to where the material will go on the exam,
it will likely go through Monday.
So we won't finish glycolysis, but we will start glycolysis.
So however for we get,
likely, I haven't decided for sure
but likely we will finish with where I finish
the material on Monday.
Today I'm going to talk most of the period about things
relating to energy and metabolic control and,
their yet another level of control that exists in cells.
You've been seeing things like covalent
modification of enzymes.
You've seen the allosteric regulation of enzymes.
But yet another consideration we have with metabolic processes
and controlling reactions is the concentration
of the substrate and the product.
Those have an enormous influence because
those are things that we have no other way around.
Cells have to work within the confines
of the concentration of materials that they have.
The reason is because the concentration of those things
determine the favorability of a reaction.
If a reaction is not favorable, it's not going to go.
So even if we control the enzyme, we have the enzyme turned on,
if the concentration of substrate and product isn't sufficient
to allow the reaction to proceed in the desired direction,
the cell has no control over that.
It's important, therefore, that we understand
the role of energy, the Gibbs free energy relative to
the control of metabolism, ultimately.
Well, metabolism is, as we will see starting on Monday,
a very sequential process.
We describe metabolic processes as occurring in pathways.
You've seen a little bit of a couple of pathways, already.
We're going to see them up close and personal on Monday.
This schematically shows us the process by which glucose
is converted from a six-carbon molecule into
two three-carbon molecules known as pyruvate.
That process is a pathway we call glycolysis.
We see that pyruvate has two possible fates in our cells,
and those two possible fates depend upon the conditions
in which the cell finds itself.
Is there plenty of oxygen or is there not plenty of oxygen?
So we see in this very simple schematic two things.
First of all, that there's a series of steps that gives
us a product, and we also see that pathways have forks.
They have different directions that they can go.
That's not unlike what we would see if we had a road map.
When we see a road map, there's several ways
of getting to Portland.
The easiest way is probably I-5,
but if there's congestion on I-5,
we could go 99 and do some zigzag way to get up
to Portland and we would get there.
So having alternate ways to get places or having alternate
responses that cells can have relative to the conditions
that they find themselves in are very, very important.
So that's just a very general thing relating to pathways.
Yeah!
You guys want to learn all that before the end of the term?
No, No.
We're not going to.
But this is actually a very nice schematic of metabolic pathways
that occur in almost every cell on the face of the Earth.
We don't really see giant fluctuations
in this schematic that's there.
What you see at each place on there,
each place you see a little node, a little knob there,
that's an enzyme, an enzyme catalyzing a reaction,
and so every place on there we see the complexity
of metabolic pathways and we realize that what cells
have to do in controlling metabolism
is extraordinarily complicated, extraordinarily complicated.
We've been tackling it a piece at a time,
regulating the enzymes,
now we're going to talk about how
the concentration of products regulates those things.
But I want you to have a feeling that,
"Wow, this is really complicated stuff in terms
"of how coordination of all this happens."
The individual reactions you'll see are not complicated.
We're going to take them slowly and we're going
to take them one at a time.
But coordinating this to get a response, overall, of the cell,
is greater than we can model on the computer right now.
We can't model the complexity of this system
adequately in a computer at the present time.
That tells you a little bit about how
complicated this process is.
Well, when we think about energy,
one of the first things that comes into people's minds is ATP.
I refer, and I've referred to this in the past,
of ATP being the sort of gasoline of the cell.
That's one way people refer to it because
it powers many things that cells could not otherwise do.
What does that mean?
Well, some reactions, on their face value,
are energetically not very favorable.
The first reaction of glycolysis, for example,
putting a phosphate onto glucose, if we just take phosphate
and glucose, and we take an enzyme
and we try to put them together,
what we discover is that energetically it's not very favorable.
It doesn't go very far forwards.
In fact, it mostly goes backwards.
But if we take that same enzyme and we use ATP instead
of just phosphate by itself, and we use the energy of ATP
to put that phosphate onto glucose,
what we discover is that that reaction becomes
much more favorable.
So ATP, the energy that's stored in ATP is used by cells
where it's necessary to drive reactions.
I want to say just a little bit about that to hopefully
give you the right impression about how this works.
One of the ways that we frequently envision
ATP working is as follows.
Well, here's a reaction.
I need to make this reaction go, so I'm going to go light
some ATP on fire, just like I would light a candle on fire,
and the energy coming off of this ATP magically
makes a reaction happen.
That's decidedly what does not happen.
It decidedly does not happen.
Energy released from ATP, if all we do is release energy
from ATP, all we will get is heat.
We will get nothing happening.
There's nothing to capture that energy.
So when we look at how the energy from ATP
is used to make a process occur, we see that the hydrolysis
of ATP is coupled to the desired reaction,
meaning that the enzyme that's catalyzing this reaction
is binding both to the molecule that the reaction
is being catalyzed on and to ATP at the same time.
Both of these are binding.
The hydrolysis of ATP then can cause a change in the enzyme.
It might cause something to be transferred, as in the example
I gave you with the phosphate moving onto glucose.
In this case, ATP is transferring a phosphate onto glucose.
But whatever the mechanism is, the important thing is that
the hydrolysis of ATP is coupled to the undesirable reaction.
It's coupled.
They're both occurring in the same place at the same time.
When I say "hydrolysis of ATP,"
I'm talking about breaking that phosphodiester bond
between the third phosphate and the second phosphate.
That hydrolysis yields ADP.
So when we say ATP goes to ADP, we've just described
a hydrolysis reaction.
That's very important to understand.
Using energy from ATP, we can make unfavorable reactions become
favorable, and that's a very, very powerful thing for cells,
as we will see as we get into metabolic pathway,
because we will see that metabolic pathways
are grouped into two categories.
One category involves what we call "catabolism."
Catabolism is the breakdown of bigger things
into smaller things.
Catabolism usually involves energy release.
It usually involves oxidation and usually
doesn't need assistance of ATP.
We'll see minor exceptions to that,
but that's basically what catabolism is involved in.
Anabolism, on the other hand,
is a process where smaller molecules are made into bigger ones.
It usually involves reduction and it usually requires input
of energy of some source, ATP being a very common one.
We'll talk about that as we get going along.
What I want to focus on now is the Gibbs free energy that
your TAs have been talking to you about in recitations.
In some cases, I'm probably going to be repeating things
that you already know, but I want to make sure that
everybody's on the same page with what I have to say here.
I trust everybody has learned from freshman chemistry,
or if not from freshman chemistry,
from the recitations, that Delta G is the ultimate
determinant of the direction of a reaction.
Yes, ma'am?
Student: I'm sorry, could you go backwards a little bit?
Kevin Ahern: Yeah.
Student: Could you say what anabolism is again?
Kevin Ahern: Anabolism is the taking of small molecules
and building bigger molecules.
It involves reduction and it usually requires input of energy.
Other questions on that, yeah?
Student: Does it usually need ATP also?
Kevin Ahern: ATP can be one of those sources of energy.
It doesn't have to be, but it can be one
of those sources of energy.
The change in the Gibbs free energy for a reaction
is the ultimate determinant of the direction of a reaction.
We can say there's nothing else that's going to get around that.
Nothing, zero, will get around the Delta G.
If the Delta G for a reaction is negative,
the reaction will go forwards, as written.
If the Delta G for a reaction is positive,
the reaction will go backwards, as it's written.
Those are rules that we're not going to be able to change.
If the Delta G for a reaction is zero,
the system is at equilibrium.
As I mentioned in class before, you've got to get out
of your head that equilibrium means equal concentrations.
It doesn't.
It means that the concentration of product
and reactant over time does not change.
The forward reaction is going at the same rate
as the backwards reaction when we're at equilibrium.
No change in concentration of products and reactants.
Now, those three principles right there are things
that we will use to understand metabolism.
Because one of the things that a cell can do to make a reaction
go forwards or make a reaction go backwards
is catalyze reactions that increase or change
the concentrations of products and reactants.
Cells can do that by controlling their enzymes.
They can actually manipulate concentrations of products
and reactants for a given reaction by
controlling enzymes being on or off.
That's a very powerful thing.
When a cell needs to make glucose, for example,
being able to manipulate those concentrations makes
the synthesis of glucose a favorable process where otherwise
it might not be.
A very, very powerful thingfor a cell to be able to do.
Well, Delta G, we recall, is defined by this reaction,
and I've simplified the equation.
Delta G is equal to the standard Gibbs free energy,
also known as Delta G zero prime,
plus RT times the natural log concentration of products
divided by the concentration of reactants.
This equation has parallels, as I've mentioned before,
to the Henderson-Hasselbalch equation.
Delta G zero prime is a constant, just like pKa was a constant.
It's a constant for a given reaction.
So if I'm talking about glucose going to glucose 6-phosphate,
the Delta G zero prime for that reaction will always be the same
at the conditions that we use, always the same,
and we're going to assume we're using
the same conditions all the time.
RT, R is the gas constant.
T is the temperature.
For our purposes, we're going to assume constant
temperature to keep things simple.
We're a warm-blooded organism.
Our temperature is pretty much constant.
Times the natural log of the concentration
of products over reactants.
Concentration of products and reactants are variables there,
and we can see how the ratio of
products to reactants can change.
We remember from the Henderson-Hasselbalch
equation the log term.
If we had more salt than acid, we had a ratio greater than 1,
meant the log term was positive.
Same is true of natural logs.
If the concentration of products is greater than
the concentration of reactants, that term is greater than 1,
it means the log term is positive.
If, on the other hand, the concentration of reactants
is greater than the concentration of products,
then that ratio is less than 1 and the log term is negative.
So we see this positive and negative nature of this log term
will have a pretty good effect on the overall Delta G.
But remember that the overall Delta G is the sum of two things.
It's the sum of a constant term, the Delta G zero prime,
and a variable term, the RT times natural log
of products over reactants.
Connie?
Student: What happens if you have more than one
product or more than one reactant?
Kevin Ahern: What happens if you have more than one product
or more than one reactant?
We actually have to take that into consideration.
I'm going to keep it simple here, so we're basically going
to work with simple considerations of this.
But if we had more than one product or reactant,
we would have to take the concentration of each
one into consideration in this equation.
Student: Okay.
Kevin Ahern: Okay?
Yes, sir?
Student: On the exam, will you provide us with numeric values
for R and T, or just have R and T in the appropriate places?
Kevin Ahern: It's a good question.
Will I give you, on the exam, values for R and T,
or let you just use that as a constant?
If I remember, I will give you values, but the important thing
is just recognizing that they're constant.
So if I forget, for some reason,
just assume they're just a plain constant.
Okay?
Yes, ma'am?
Student: I should probably remember this,
but G naught prime, is that room temperature?
Kevin Ahern: G naught prime is defined for a specific set
of conditions, yes, and it's not room, it's 25 something,
25 degrees, whatever that turns out to be in Kelvins.
Student: But it's not zero T.
Kevin Ahern: It's not zero, no.
Student: Yeah.
Kevin Ahern: But, again, we're going to assume that
we've got everything at that one set of conditions,
just to keep it simple, but, yes,
Delta G zero prime is a constant,
but it's a constant for a given set of conditions.
That's important to recognize.
Yes?
Student: So kind of, with the solving of any Gibbs equations
on the test, is that going to be very much like solving
our pH/pKa equations where...?
Kevin Ahern: So her question is, is the solving of Gibbs
free energy equations going to be like
Henderson-Hasselbalch equations?
I would be amazed if it weren't, because, again,
what I want you to get is the big picture.
I'm not having you chase numbers.
I'm not expecting you're going to memorize logarithms
or any of that, but you should know how that log term's
going to change and how that's going to affect
the value of Delta G.
Yeah, absolutely.
Student: Just quick question.
Is temperature in Kelvin?
Kevin Ahern: Temperature's in Kelvin, yeah.
I'm not going to trip you up and say, "Here is it in centigrade,
"and snicker, snicker, snicker,
"You didn't put it in Kelvin and now you're wrong
"and now you're stupid."
Okay?
[laughing]
The important thing is getting the big picture,
not tricking students.
I really don't want to trick anybody.
I could lie, then I'd really trick you!
Ha-ha-ha-ha-ha!
I'm not going to do it.
Student: Is there only [unintelligible] for the second midterm?
Kevin Ahern: His question is, is there only one calculation
question for the second midterm?
The answer is, I'm not going to say anything about it.
I'm not going to tell you what the second midterm is.
The format will be exactly the same as the first midterm.
You saw there was a section that related to calculations
and that section had a certain number of points.
I can't tell you how many calculations will be there.
You should know how that equation alters as the concentration
of products and reactantsóor as I put on the thing there,
B over Aóactually changes.
I think, again, you learned that, hopefully,
with Henderson-Hasselbalch.
It's fairly straightforward to understand.
One of the places where students trip up is they forget
that Delta G zero prime is a constant
and Delta G is not a constant.
So remember that.
Delta G is a variable, and it varies as the concentration
of products and reactants change.
But the constant in the equation is the Delta G zero prime
for the given set of conditions that we're going to be using.
Now, look through the problems that I've put online for you.
The TAs have worked through some of those problems
and there's also problems in the book.
If you're confused or you have issues or questions,
as always, please feel free to come and see me.
Believe it or not, my schedule, which has been pretty impossible
to catch me, is actually lightening up next week,
so I should have more time available to meet with
anybody if you have questions.
Anytime you have questions and I'm not available at
the times it's convenient for you, you're always welcome
to send me an email and I will schedule a time to meet with you.
So I want you to have opportunity to connect, as necessary.
Let's take a little diversion here,
thinking about energy in another way.
Molecules we can sort of think of as having a sort
of inherent energy associated with them.
We sort of intuitively think of this.
We think of, again, gasoline.
Gasoline has a fair amount of energy in it.
When we oxidize that gasoline, we generate heat.
In an automobile, of course, that heat is used to move cylinders
and to, ultimately, give motion to the vehicle.
In our muscles, ATP has a lot of energy, and the energy of ATP
is actually used to favor muscular contraction.
It's because of that type of gasolineóin this case,
ATPóthat we're able to move.
We will see as we move through biochemistry
that there are molecules that have various energies.
This is not a great example, but it's an example
of a molecule that has a phosphate on it.
As I've sort of alluded to in class,
molecules that have phosphates on them tend to have more
energy in them than the same molecule without the phosphate.
So if I take off the phosphate here,
I'm left with glycerol, and glycerol 3-phosphate
has more energy than glycerol by itself does.
Well, if I want to make a more energetic molecule,
I have to take that into consideration,
starting with a glycerol.
So one of the ways I can do that,
in making a glycerol 3-phosphate,
is by coupling the addition of a phosphate to glycerol
by the hydrolysis of ATP, kind of like I described earlier.
And that energy of hydrolysis of ATP will favor the putting
of the phosphate onto that glycerol
and making a glycerol 3-phosphate.
You might wonder how the energy arises from ATP.
While I'm not totally fond of this figure,
we notice that when we think of ATP,
we think of the fact that we've got this adenosine molecule
and on its 5-prime end we have three phosphates.
one attached to the other, attached to the other.
So we've got phosphate, phosphate, phosphate,
and these three phosphates are all negatively charged.
They really don't like each other.
So we could imagine that, given the choice,
if they have the opportunity, they will,
in fact, repel each other and get away.
It's that repulsive nature of the negative charges
within those phosphates that ultimately give rise
to the energy of ATP.
ATP doesn't go flying apart because the electrons
that are found in the phosphates can be rearranged
in a resonant fashion, as you see on the screen.
So they can sort of swap the electrons back and forth,
and because of that, the triphosphate bond is not going
to fall apart automatically.
But when it is hydrolyzed, that repulsive nature
of the phosphates is going to yield energy.
This is a table.
I'm not going to expect you to memorize this or anything,
but I just show you this to show you the various energies
associated with some high energy molecules inside of cells.
The energies associated here may surprise you a little bit.
There's the energy of ATP.
That is, the hydrolysis of ATP to ADP gives this much
energy in terms of kilojoules per mole,
or this much energy in terms of kilocalories per mole.
They're just difference of units is all they are.
That negative number tells you that, first of all,
it's a favorable reaction.
This is the Delta G zero prime, the standard free energy
I may have said "Delta G, I meant, Delta G zero prime"
of the hydrolysis of these.
What we see is that there are molecules in the cell
that have a higher energy of hydrolysis than ATP.
Now, if ATP is the gasoline that powers the cell,
how in the world does a molecule like ATP,
which doesn't have that much energy in it,
favor the synthesis of molecules that have even more
energy inside of them?
Well, you might look at this and say,
"Well, maybe they use two ATPs or three ATPs,"
and the answer is, cells don't have that option.
Cells have to make molecules that have high energy,
higher energy than ATP does, and to do that,
they have to be able to take other things into consideration.
The number one thing they'll take into consideration,
as we will see, is the Delta G equation itself.
Look at this reaction.
This is an interesting reaction.
Here, this reaction is showing us how the body synthesizes
one of those high energy molecules.
If you go back and you look at that table I just showed you,
there's creatine phosphate, right there.
It's got more energy in it than ATP itself does.
How do we put that in there?
Well, here's the reaction that the cell goes through.
We can see ATP is, in fact, an energy source for this reaction,
and we can see that the overall Delta G zero prime for this
reaction is positive.
What that means is, if I start with equal concentrations
of products and reactants... let's plug the numbers in here.
If I have an equal concentration of B,
which is creatine phosphate, and I have an equal
let's say creatine phosphate and ADP,
and I have an equal concentration of creatine ATP,
this value is 1.
The log term is zero, right?
That means that the Delta G will equal the Delta G zero prime,
which is a positive number, which means the reaction
goes which direction?
Student: Left.
Kevin Ahern: Backwards.
How do I make that reaction go forwards?
How do I make the overall Delta G be negative?
The only thing I can change is change the concentrations
of the products and reactants.
So if I dump in a bunch of reactant,
then I make the reaction go forwards,
because that's going to make this log term up here
be more negative, and if I make it negative enough,
the overall Delta G is going to be negative.
Now, this turns out to have great physiological relevance.
The great physiological relevance is this, okay?
So creatine phosphate is used in our muscles.
I'm going to bitch about creatine in a minute,
but creatine phosphate is used in our muscles,
and it's used kind of like myoglobin is used for oxygen.
Remember I said myoglobin was a great way of storing oxygen?
And when the oxygen concentrations got low, what happened?
That's when myoglobin gave up its oxygen,
but only when it got very low.
It turns out creatine phosphate is used to make ATP
when cells run out of ATP.
Let's think about this.
I am going out and I am going to run a 100-yard dash.
I get to the starting line.
The gun goes off, and I take off and I start running,
as fast as I can.
What's going to happen?
Well, muscular contraction requires ATP.
I start out, my ATP concentration is fairly high,
so this reaction has been driven fairly far to the right,
but I've got enough ATP to get started.
I go a few yards and, before metabolism starts kicking in
and epinephrine starts flowing and all that adrenaline
starts running, before all that can happen,
my ATP levels inside of my muscles fall very quickly,
because I'm burning it as fast as I can run.
Which, for me, isn't very fast,
but I can still burn it fairly fast.
What happens when my ATP concentrations go down?
What happens to the Delta G of this reaction?
It starts going more positive,
and it starts going more positive, the reaction starts
going back to the left, and when it goes back to the left,
look what we make, ATP.
We don't have to do anything.
Our cells don't have to have any controls.
They don't have to have any brains.
All they have to have is this equation, right here,
such that when I take off and I start unbalancing
this equation by running, this equation rebalances itself
by making ATP, because it uses this stuff right here
and this stuff right here to drive it backwards.
That's really cool!
Then, when I finish my race and I grab that piece of pizza
and mug of beer to celebrate the fact that I just won that race,
I'm not burning ATP anymore and I'm putting all kinds
of energy in my body that's going to make ATP.
ATP concentrations start going high.
What's going to happen?
Well, the reactants are going to get larger in concentration
and this reaction is going to move to the right,
and I will go back and I will store creatine phosphate.
Thus, cells can make a high energy molecule that's higher
than the energy of ATP simply by concentration.
It tells us that concentration is absolutely critical
for making molecules, absolutely critical,
and it's magical enough that we can actually make higher
energy molecules simply by altering concentrations
of products and reactants.
That's a really phenomenal thing.
Now, I promised I was going to bitch about creatine, so I will.
One of the most common questions I get is,
"So, creatine, I hear about that I can really improve
"my athletic performance by taking creatine and all this!
"And all my friends are taking this stuff and it's really great!
"They say it makes them feel really like they've
"got a lot of energy!"
I say, "Okay, well, let's think about this.
"I'm going to go run this race, so, in about an hour,
"so I'm going to go take a whole bunch of creatine.
"Wow, man!
"I'm going to be so winning this race, right?"
Well, let's look at this equation.
When I start taking a whole bunch of creatine in my system,
which way is this reaction going to go?
[laughing]
Student: Right!
Ahern: And if I've got a whole bunch of creatine sitting there,
is it going to go back?
No!
Duh-uh.
Then I get the second question.
"Well, what if you took a whole bunch of creatine phosphate?"
[laughing]
Well, if you took a whole bunch of creatine phosphate,
wouldn't you ultimately be increasing your concentration
of creatine over here, as well, so in the longer term
you're going to have more of a problem?
Yes.
Should you be playing with Mother Nature here?
No!
Might you feel differently?
Probably.
The brain's a very easily malleable thing.
If you think that something is going to happen,
you may very well feel that happen.
Does it alter athletic performance?
It probably does, to some extent.
Is it good for you?
I would probably say "no."
But you could certainly see, in the context of this reaction,
that taking creatine just before a race might not be
the smartest thing for you to do.
It just might not be the smartest thing for you to do.
Questions about that?
I'm rambling and griping and all that sort of stuff.
Connie?
Student: Okay, so you have increased amounts of creatine
ATP despite the fact that [unintelligible]
it will go in that direction?
Kevin Ahern: If I make enough of this stuff,
it's going to favor it going to the right.
Absolutely.
Student: But you also said, earlier, that creatine phosphate
has more energy than ATP, and you can't go,
maybe you'll use two ATPs, so where does that extra
energy come from?
Kevin Ahern: Where does the extra energy come from?
It comes simply from the concentration.
That's what this reaction,
that's what this equation is actually telling us,
that we gain energy as a result of concentration.
There's energy from concentration.
Yes, sir?
Student: What about when you add creatine to your body,
like, way before you exercise, say you've just...
Kevin Ahern: See, this is a guy that's been talking
to these people.
"What happens if you do it way before?
"Hey, I'm going to figure out the right time to take
"this stuff and it's going to go."
As I say, you probably do have,
I'm not trying to pick on you, here.
It probably does have an effect on performance,
but it's hard to predict where you're going to get that
sweet spot and where you're not going to get that,
and that's why I'm saying it's probably not
a good idea to mess with it, but you're right.
There are considerations with that,
and there are some studies that suggest
that you may increase it somewhat.
The thing that I say to those is, you know,
there's all kinds of things that you can do
for athletic performance, but increasing athletic performance
does not mean increased health.
If you look at the lifespan of professional athletes,
it's lower, on average, than that of nonprofessional athletes.
Students frequently have the notion that
maximizing athletic performance is the best thing
that you can do for yourself, and it's not.
It's only good for running footballs,
and it's only good for running races,
and it's good for hitting baseballs,
but it may not be good for health.
So that's important to keep in mind.
That's why I gripe about it.
Other comments or questions?
Everybody's going to go see if they can find
some creatine phosphate now, I can see.
Student: Can I ask you a question?
Kevin Ahern: Yeah.
Student: On that list you showed us of high energy molecules,
one of them was a 1,3-bisphosphoglycerate.
Student: Is that related to the 2,
3- bisphosphoglycerate we had earlier?
Kevin Ahern: Good eyes!
His question was, I showed this table that
had 1,3-bisphosphoglycerate in it.
Is it related to 2,3-bisphosphoglycerate that
I talked about before and where did i show it there?
It's right there.
It turns out that it is indirectly related to it, yes.
And we'll see, when we watch how this guy is metabolized,
actually, not this guy, but the product of this guy
is metabolized, we'll see how 2,
3- bisphosphoglycerate comes about.
It doesn't come directly from this,
no, but it is related.
Student: Is there any known enzyme that transfers one
of those phosphates from a 1 to a 2 position,
or vice versa, so it could be used as an energy source?
Kevin Ahern: His question is, are there enzymes that
convert 1 to 2 to make a 2,3-bisphosphoglycerate
from 1,3-bisphosphoglycerate?
There are some people who say that's the way that
it actually forms, and so there are enzymes that may be invovled
in that, but I will show you a much more important consideration
when we look at glycolysis itself.
Because of this consideration in glycolysis,
you'll see that you don't have to worry about
this enzyme converting 1 into 2.
Kevin Ahern: Oh, there we go.
I've gotten pretty good at recognizing the damn thing.
All right, other questions?
How are we doing on time?
There's our reaction I've just finished there.
What I've been telling you all along are the considerations
that we have for our body.
This, in summary, this is what our body
is always concerned about.
The cells of our body are always concerned about this.
Our body has to do certain things and these things
that it has to do require input of energy.
They include moving, in the form of muscular contraction.
They include active transport, as we'll talk about next term,
where they're moving things across a membrane.
Biosynthesis, if we want to make glucose from simple
starting materials, we've got to put energy in to do that.
And signal amplification, we're transmitting information
down a nerve cell, we have to have energy to be able to do that.
Ultimately, the energy for all of these processes
is coming from ATP going to ADP, or something equivalent.
Well, how do we get ATP?
We get ATP from the processes on the bottom,
and these largely involve oxidation or photosynthesis.
Since we don't have the option of photosynthesis,
we're stuck with oxidation, which means that we're eating
things that plants have made, ultimately.
So oxidation makes ATP.
These processes use ATP.
We have to balance these if we hope to be effective.
When I say "oxidation"
it's important to understand what that means.
Oxidation means the loss of electrons.
The process of losing electrons is the process of oxidation.
Now, as you'll hear me say many times,
electrons don't just disappear.
In chemical reactions, we can't create or destroy matter.
So when I say "loss of electrons,"
I'm not talking about them evaporating.
Those electrons have to go somewhere.
We'll see cells have some very, very cool ways
of handling those electrons.
The handling of those electrons turns out to be
very critical for making ATP.
Some very cool ways that cells do it, but, for the moment,
we're just going to concern ourselves with the loss
of those electrons.
If I go from methane to methanol,
I've gone through an oxidation.
By the way, "oxidation" doesn't equate with "oxygen."
In this case, we see an oxygen getting put on.
But we don't see another oxygen getting put on here,
yet it's an oxidation.
Oxidation simply means, as I said, the loss of electrons.
In going from here to here, this carbon has lost electrons.
Losing electrons.
If I go from here to here, I've lost electrons.
I go from to here, I lose electrons.
I go from here to here, I lose electrons.
And, at this point, I have carbon at its highest oxidative state,
meaning I can't oxidize this guy any further.
The Delta G zero primes for each of these reactions goes
from minus 820, telling me there's a lot of energy in here,
minus 703, there's a lot of energy in here, minus 523,
there's a lot of energy in here.
Each time we go down, we see there's less energy
because what's happened?
Some of that energy was given up in making this.
Some of that energy was given up in making this.
Some was given up in making this, and, finally,
some was given up in making this.
Carbon dioxide is the ultimate oxidation product
of metabolic processes... the ultimate oxidation product
of metabolic processes.
That's why we exhale carbon dioxide.
It's of no more use to us, folks.
It does us no more good.
We can't get any more energy out of it,
so let's get it out of our system and get something else
that's going to get us some more energy.
An alcohol is at a more reduced state.
As we go from right to left, we're more reduced;
as we go from left to right, we're more oxidized.
Methanol is more reduced than formaldehyde,
but it is more oxidized than methane.
What you see on the screen are two of the most important
energy sources for cells: glucose and fatty acids.
Fatty acids, of course, are stored in fats.
These guys have very, very different ways
of being handled in our body.
They both get oxidized.
They both get oxidized.
In fact, fatty acids have more energy in them,
per carbon, than glucose does.
If we calculate energy per carbon,
there's more energy in fatty acids than there is in glucose.
You could look at this and think, well, that sort of makes sense.
Most of the carbons here are carbon hydrogens.
Most of the carbons here are carbon hydroxides.
This is starting out at a higher oxidized state
than this one is.
But I said they're handled in the body very differently than
that is, the two are handled very differently from each other.
Why is that?
Well, it turns out glucose is water soluble.
Our body can dump glucose into our bloodstream
and do nothing more with it.
It dissolves.
It flows in the blood nicely and everybody's happy,
and since the blood is flowing through our body rapidly,
it gets to its targets very quickly.
and we need to escape from that grizzly bear that's
chasing us, our muscles have that glucose in seconds.
Fatty acids, on the other hand, aren't very water soluble.
They're usually tied up with glycerol to make fat.
Fat is completely water insoluble.
But fat, also, if it wants to give us the energy that we need,
it has to travel through our bloodstream.
But moving something through our bloodstream
that is not water soluble is a real problem.
Fat has to be packaged up into bundles.
You've heard of LDLs and HDLs?
These are the bundles that fat and fatty acids
are carried in in our body.
It takes a while to make those.
Fatty acids are not very good sources of quick energy.
Glucose is a wonderful source of quick energy.
So our body burns glucose very readily.
I'll talk about that later.
There's the 1, 3- bisphosphoglycerate.
This is a really interesting example about how cells
are combining a couple of things in one process.
I'll talk about it when I talk about glycolysis on Monday,
but suffice it to say that this reaction is a very important
reaction in our cells because it involves oxidation.
We see this going from an aldehyde to an ester.
That oxidation transfers electrons to an electron carrier,
known as NAD, to make NADH, and, yes,
electron carriers are the magic that cells have
for dealing with those electrons.
The energy of this oxidation is used to put a phosphate,
all by itself, onto this molecule over here.
Those three things really turn out to be very cool
when we talk about how glycolysis works.
Because we've made this molecule, right here,
that has high energy, this guy, now, you saw in
that table I showed you before, had more energy in it
than ATP did, it becomes really easy for this guy
to transfer its phosphate onto ADP and make ATP.
This is one of the ways in which we make ATP in the cell.
It's not a common way, but it's one of the ways
in which we do it.
More importantly in our cells,
and we'll talk about this next term,
the way that we make ATP is by the use of mitochondria
and gradients of protons.
It's a phenomenon known as "electron transport"
and "oxidative phosphorylation."
The best analogy I can give you for this is that
of charging a battery.
We'll see that cells use the process of oxidation to charge,
literally, charge a battery.
Student: That's electron transport and what else?
Kevin Ahern: Oxidative phosphorylation.
So we charge the battery and then the charge
of that battery is used to make ATP.
Electron transport is the process whereby we charge the battery.
Oxidative phosphorylation is the process
where we use the charge of that battery to make ATP.
That's how the vast majority of ATP
in our bodies is actually made.
I talked about catabolism briefly earlier in the lecture.
Suffice it to say that catabolism involves breaking
down large molecules into smaller molecules.
Here are some metabolic pathways in the process.
The upshot of all of this is we get ATP out.
In general, catabolic processes, as I said,
take large molecules, break them into small molecules.
It involves oxidation and it releases energy
that's captured in the form of ATP.
Anabolism is the opposite of this.
We take small molecules.
We build them into larger molecules.
It requires reduction and it requires input of energy.
Now, let's spend a minute talking about electron carriers.
Cells are set up in a very interesting way so that
the oxidations that occur in cells are
fairly small in nature, relatively small.
What does that mean?
It means that the energy released in any given oxidation
in a cell doesn't give up too much energy.
Another consideration is, if oxidation involves loss
of electrons, handling those electrons is critical,
because if the electrons are simply lost,
they go onto molecules and make very reactive molecules
that may cause problems reacting with things that we don't want.
Cells are control freaks.
They don't want to have molecules reacting on their own,
so rather than letting those electrons go onto whatever
the first thing happens to be that gloms onto them,
cells transfer electrons to specific carriers that
hold onto those electrons and keep them from creating
other reactive molecules.
That's a very important consideration.
The electron carriers that cells use,
there are three main ones that we will talk about.
One of these I just showed you.
It's known as "NAD."
No, you don't have to know the structure.
NAD is the oxidized form, meaning it is lacking
a couple of electrons.
If I transfer two electrons to NAD,
I usually transfer one proton,
as well, and that gives me NADH.
When you see NADH, you're seeing the reduced form.
It's already gotten a proton and two electrons.
There's a related molecule known as NADP.
NADP is the oxidized form and when it gets two electrons
and a proton, it becomes NADPH, NADPH being the reduced form,
NADP being the oxidized form.
The third category of molecules involved in carrying
electrons are the flavins, FAD, flavin adenine dinucleotide.
FAD is the oxidized form, lacking those two electrons.
If I put two electrons onto FAD, I usually put two protons,
as well, and I make FADH2.
So FADH2 is the reduced form and FAD is the oxidized form.
We'll see next term what happens to those molecules once
they've gotten the electrons in them.
There's actually energy being stored in these molecules
by holding onto those electrons.
One of the ways in which those molecules can use
those electrons is to reduce something else.
Look at this reaction here.
Here is an alcohol.
An alcohol is being oxidized to a ketone.
That involves loss of electrons.
Where are those electrons going?
Well, they're being put onto NAD+ and making NADH.
This is the most reduced form of the carbon is here.
The most oxidized form is here.
The most oxidized form of the carrier is here,
and the most reduced form of the carrier is here.
I always like to say that for every oxidation
there's an equal and opposite reduction.
It's true.
This guy's getting oxidized.
This guy's getting reduced.
What if I go backwards?
Can I use those electrons of NADH to make this?
I certainly can.
So one of the things I can do is use this as a repository
for holding onto electrons.
That's a good place to have a song, I think, and call it a week.
What do you guys say?
What's that?
Student: [unintelligible] good part.
Kevin Ahern: The good part.
So this is a very short song.
It's about Delta G.
It's to the tune of "Danny Boy."
[all singing]
Lyrics: Oh, Delta G, the change in the Gibbs free energy,
can tell us if a process will advance.
'Cause if the value's less than naught it translates
that reverse reactions haven't got a chance.
But when the sign is plus, it is the opposite,
and then the backwards happens all the time.
A factor is the standard Gibbs free energy.
So don't forget about the Delta G naught prime.
See you guys on Monday.
[indistinct conversations]
[no audio]
[END]