– [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
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..