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- [Voiceover] So let's give ourselves
an overview of glycolysis.
and glycolysis is an incredibly
important biochemical pathway.
It occures in practically all life as we know it
and it's all about taking glucose as a fuel and,
in the process of breaking it up,
lycing the glucose, glycolysis,
breaking it up into two pyruvate molecules.
Glucose is a six carbon molecule.
Each of the pyruvates are three carbon molecules.
In the process of doing that,
you produce two ATPs net.
It actually turns out that you need to use two ATPs
and then you produce four.
So you use two ATPs.
That's often called the investment phase
and we'll talk about that in a second.
And then you produce four ATPs
for a net of
plus two ATPs
and that's what we see right over here.
You see a net of two ATPs being produced directly
by glycolysis, and then you also have
the reduction of NAD to NADH.
Remember, reduction is all about gaining electrons,
and over here, NAD, that's nicotinamide
adinine dinucleotide, we have other videos on that,
it's an interesting molecule, it's actually a
fairly decent-sized molecule, we see this
positive charge, but then we see that not only
does it gain a hydrogen, but it loses its positive charge.
It gains a hydrogen and an electron.
You can think on a net basis it's gaining
a hydride.
Now a hydride anion's not going to typically be
all by itself, but on a net basis, you can think about
that's what's happening.
And so it's gaining a hydrogen and an extra electron
and so this, the NAD+, this is going to get reduced.
That is going to get reduced to NADH.
So this is getting reduced to NADH.
And that NADH, it can then
be oxidized in the electron transport chain.
We'll study that later on when we think about
oxidative phosphorylation, to produce
even more ATPs.
But on a very high-level, simple basis.
Glucose being broken down in pyruvate,
six carbons, three carbons each of these
pyruvates, now there's other things attached
to the carbons, and we'll see that in a little bit.
Two ATPs net generated, and you have the reduction
of two NADs to two NADHs, and those can be used
later on to produce more ATPs.
Now, glycolysis is typically just the beginning
of cellular respiration.
If oxygen is around, then you have these products,
some of these moving into the mitochondria
where you can have the citric acid cycle,
Krebs cycle, and the oxidative phosphorylation occur.
If you don't have oxygen around, then you're
going to do anaerobic respiration, or you're
going to go into fermentation.
We'll talk about that in a future video, and that's
really about figuring out what to do with these
products, and especially replenishing your NAD+.
Now that we have a very high-level overview
of glycolysis, let's get a better appreciation
for exactly what's going on.
And whenever I look at these more detailed
processes, the one thing to just appreciate
is how much complexity is occurring
in all of your cells right now.
This is fairly abstract,
to even imagine these things, but this
is happening throughout your body
gazillions of times, right now.
This isn't something that is somehow
distant from you.
And it's also fun to appreciate, well how
all of this was discovered by scientists.
That's a whole other fascinating discussion.
But the whole point of this video is just to
give us an appreciation for the actual mechanism
or the reaction by which it occurs.
I'm not gonna go into the detailed
organic chemistry mechanism.
So over here, this is a glucose molecule over here,
you see one, two, three, four, five, six carbons.
And then the first step is, it gets phosphorylated
and we have a whole video on the phosphorylation
of glucose, and all of these steps are facilitated
with enzymes.
The phosphorylation is facilitated with the hexokinase.
Kinase is a general term for an enzyme
that either facilitates phosphorylation or
dephosphorylates, it's dealing with
phosphorylation, I guess you could say.
And enzymes are all about lowering
the activation energy.
And the way that hexokinases do, or part of
how they do it, is they involve the cofactor,
a magnesium ion.
And we've talked about that in other videos,
how cofactors can help an enzyme lower the
activation energy.
And to do the phosphorylation, we use an ATP.
So this is minus one ATP.
So we are in the investment phase.
But this reaction strongly goes from
left to right, it's a coupled reaction that,
phosphorylating the glucose, that
requires free energy, but the ATP releases free energy
you couple these reactions, it strongly goes from
left to right.
Now, and just to be clear what happened,
this over here got replaced, or maybe
I should say this over here got replaced
with that over there.
Just to keep track of what's happening.
Now, another enzyme-catalyzed reaction,
this one is actually an equilibrium, it can
go both ways, but as we'll see, the right
side or the things that are further into the
glycolysis process, these are constantly
being turned into further products, so their
concentrations are going to go down, and so
the reaction will tend to go that way.
Although this particular reaction, going from
glucose 6-phosphate to fructose 6-phosphate,
this could be an equilibrium.
But the enzyme that facilitates this,
phosphoglucose isomerase, these are
enzymes that help go from one isomer of
a molecule to another isomer.
And that's what's happening here.
Instead of this oxygen being bound to this carbon,
this bond forms with this carbon.
So you have fructose, you have the five-carbon
ring over here, or you have the five-element
ring, you have four carbons in it,
versus a six-element ring where right over here
you have five carbons.
So this bond goes to this carbon right over here
and that's the main difference.
And then you have another, very strong
forward reaction, once again facilitated
by ATP, and this is done by phosphofructokinase.
It has the word kinase in it.
And it's using up the ATP, you can guess
what's going to happen.
We're going to attach another phosphate
group to the fructose 6-phosphate, and now
you have two of these phosphate groups.
So this hydrogen right over here is now
replaced with another phosphate group.
And once again it's facilitated by the
magnesium cofactor, it helps stabilize
some of the negative charge associated with
the phosphate groups, we talk about that in other videos.
But the important thing is, it uses another ATP.
We're still in the investment phase,
negative one ATP.
And every time I look at this it's just fascinating
that all of this stuff is happening in your cells
as we speak.
In fact, in order for me to speak this has to happen,
because my body needs to take glucose and come up
with some energy to turn into ATPs so that my muscles
can actually move and I can actually inhale and exhale
and all the things that I need to do for speech.
So appreciate what's going on over here.
Now the next step we talk about, the whole
process of glycolysis is lysing glucose.
And over here this is derived from
glucose and some phosphates, and the
next step, we're actually going to break it up.
And we're going to break it up using the enzyme
fructose biphosphate aldolase.
Aldolase enzymes facilitate the aldol reaction.
And this one, the aldol reaction could be
to merge two molecules or in this case,
we're going to break them up.
And we break them up into two three-carbon chains.
Now these two three-carbon chains,
glyceraldehyde 3-phosphate, and this character
right over here, they can be converted between
the two with another isomerase, this
triosephosphate isomerase right over here.
So at this point in glycloysis, we can think of ourselves
as really having two of these.
So let's say two times glyceraldehyde 3-phosphate.
So as we go further on, just imagining
this happening twice for every glucose molecule.
And any time you get confused, I encourage you
to pause the video.
See how these pieces and these pieces
put together, can form that over there.
So now we have another reaction,
it's facilitated by a dehydrogenase.
Dehydrogenases usually are involved in
this case, this is the reduction of NAD.
We saw that in the overview video.
So NAD is being reduced.
And this can be used, this NADH later on
can be used in the electron transport chain
to potentially produce some more ATP,
but in that process we also add
another phosphate group to the
glyceraladehyde 3-phosphate.
So you see this phosphate group
right over here that wasn't there before.
And actually this right over here is
I should have arrows on both sides,
this right over here, that reaction
could actually go both directions.
Actually, that reaction can as well.
And then, we are now
going to be in the payoff phase.
So this right over here, we're starting
with this molecule that has these
two phosphate groups, and then
using the phosphoglycerate kinase, we're
able to pop one of those phosphate groups off
and in the process, produce ATP.
Now we might want to say plus one ATP,
but we have to remember, this is now
happening twice.
Cuz we had two of those glyceraldehyde 3-phosphates,
so now we could say, if we're talking about
this happening twice, plus two ATPs.
We are now in the payoff phase.
Then you have, facilitated by the
phosphoglycerate mutase, a mutase is a
class of isomerases.
I have trouble saying that.
That'll take a functional group from one place
to another, or take one part of a molecule
to another part, and you see this phosphate group
moving on from this carbon to the middle carbon.
And so that's what that's doing.
Then we use an enloase to get over here
and then the pyruvate kinase, and here
the kinase is going to be used to
dephosphorylate this molecule right over here,
and it gets us to the way I've drawn it is
pyruvic acid, since I've drawn the hydrogen here,
and if the hydrogen is let go and this oxygen
hogs the electron, we would call this pyruvate.
And this is considered to be the end of,
I guess you could say, mainstream glycolysis.
But what happened, and I don't want to
glaze over what happened over here,
this ADP got converted to another ATP, but it's
going to happen twice.
So this is another plus two ATPs.
So hopefully you see the investment phase,
we use an ATP right over here to phosphorylate
the glucose, we use another ATP right over here
to throw that second phosphate group
on what was the fructose 6-phosphate,
but then we get the payoff phase.
So we're able to produce this NADH, and
this is actually going to be two NADHs,
because everything here's going to happen
twice now, we can assume that this character
over here also gets converted to a
glyceraldehyde 3-phosphate, and now
we've produced two ATPs, cuz this is happening twice,
and we've produced two ATPs right over there.
So hopefully everything we talked about in the beginning
actually makes sense.