- [Instructor] Alright, so, if we were gonna go
on the ambitious task of tallying up
how much ATP was produced in one cycle
of cellular respiration or, just to be super clear here,
I mean how much ATP was produced
per the oxidation or breakdown
of one molecule of glucose
in cellular respiration?
We might start off by just getting ourselves organized
and reminding ourselves that there are
two kind of main ways that we produce ATP
in cellular respiration so,
the first minor contribution comes from something called
substrate level
phosphorylation.
And remember that this is exactly what it sounds like,
we have a substrate, or a molecule, I'm just gonna say R.
And remember that in the context of cellular respiration,
this is usually, we think of this as a
kind of metabolite, an intermediate metabolite of glucose,
so somewhere along glucose is oxidation.
We get a metabolite and we activate this metabolite
with a phosphate group.
And from this phosphate group,
we can actually donate it directly to ADP
to produce ATP,
and of course our molecule also
gets modified in the process,
usually gaining a hydroxy group,
but the details aren't entirely important
except to realize
that this phosphorylation is occurring
at the level of a substrate.
This is in contrast, of course,
to oxidative phosphorylation,
which is where we get the bulk of our ATP.
And this oxidative refers to the fact that
this process requires oxygen
and in fact, the importance of oxygen here is that
this oxygen is reduced
by electron carrier molecules
and something called the electron transport chain
so, remember that we have a electron carrier molecules
called NADH and FADH two
that are produced at various stages of cellular respiration,
glycolysis, the oxidation of pyruvate,
the Krebs Cycle,
and it's basically storing up all of that energy
from the glucose molecule and it's gonna donate it
into the electron transport chain,
and of course the final electron acceptor
is oxygen, which is then reduced to water.
But the important here is that this flow of electrons
is able to power something,
essentially fuel something called ATP synthase
which is an enzyme that is
in the mitochondrial membrane
that produces the bulk of our ATP.
Now, the next point I want to make here is that
it's actually been possible for us to calculate
the exact number of ATP produced
in substrate level phosphorylation and we've also
nailed down the amount of NADH
and FADH two molecules that are produced
in this process as well.
But for a quite a while, it was difficult to nail down
the exact number of ATP molecules
that were produced in oxidative phosphorylation.
And for this reason, actually,
and I'll get back to kind of why we're unable to,
you know, kind of nail down a number here
but for this reason, you might often see
quite a range of predictions
for how much ATP's actually produced in
one cycle of cellular respiration,
just to give you an idea of that, you know,
when I look at some textbooks, you can see
a range of anywhere from 30
to 38 molecules of ATP that are predicted
to be produced for the oxidation of one molecule of glucose.
So, of course, to get back to this kind of
elusive calculation of ATP,
researchers have done controlled studies
in which they basically take a known amount of NADH
or FADH two
and they have mitochondria available in the lab,
and they basically allow the mitochondria
to oxidatively phosphorylate these molecules
and essentially measure how much ATP is produced,
but kind of to their surprise at first,
they found that for NADH,
for one molecule of NADH, they calculated,
there was not a whole number of ATP produced,
in fact, they found that there was somewhere between
two to three ATP molecules produced
for every one NADH molecule.
And for FADH,
they also found that there was no whole integer number
of ATP but rather, there was a range,
somewhere between one to two
ATP produced.
Now, for the longest time, researchers kind of
looked at these results and said,
"You know, whole numbers are a lot easier to deal with,
"and so, why don't we just assume,
"for the sake of assumption,
"that we can kind of round up,
"and we'll say that for every one molecule of NADH,
"let's say that we have three molecules of ATP produced.
"And for every molecule of FADH two, rather,
"we have two molecules of ATP produced."
And so, using these kind of estimations,
they calculated essentially the upper range of ATP
so, these calculations were ultimately used
to calculate kind of this number
of 38 ATP produced in cellular respiration,
kind of the upper limit of ATP produced.
But of course, we still have this range and in fact,
it's worth kind of pausing to stop and think about
for a second,
if it is surprising that we have this range
in the first place.
And so, to think about this a little bit further,
I wanna go ahead and kind of just draw out
without getting too detailed,
kind of a depiction of what's going on
in the electron transport chain, so remember,
that the electron transport chain is taking place
in the mitochondria, and the mitochondria
has two membranes: we have the inner mitochondrial membrane,
general label here is I,
and we have the outer mitochondrial membrane.
And along the inner mitochondrial membrane,
we have a series of proteins that
are known as protein complexes.
And you know, these all have specific names,
but just for our purposes,
it's important to recognize there are kind of just
four main protein complexes,
and in some textbooks,
people will actually call
ATP synthase, which I'm gonna go ahead and draw here
in yellow as complex number five,
so let me go ahead and label these,
one through five,
just so we remember that,
so, these four represent the protein complexes
that shuttle electrons and of course,
five represents ATP synthase.
Now, recall that the basic premise here is that
these reduced electron carriers donate electrons
to the electron transport chain and in fact,
specifically, NADH donates
two electrons to protein complex number one,
and FADH two donates two electrons
to protein complex number two.
Now, the second important point is that
as these electrons are kind of flowing down these proteins,
for every two electrons that kind of flow by,
it's actually been calculated that
protein complex number one pumps four
protons into the intermembrane space,
protein complex three, it pumps, also, four protons,
and protein complex number four
pumps two protons.
And protein complex number two doesn't really contribute.
Now, with these facts in mind,
we can go ahead and actually calculate
how many protons are pumped for a molecule of FADH two
and how many protons are pumped for a molecule of NADH.
So, let's go ahead and just quickly do that here,
so because NADH donates at the very first electron complex,
it contributes to a total of four plus four plus two,
or ten protons are pumped out
for every molecule of NADH.
On the other hand,
FADH two enters in complex number two,
so it only contributes to the total pumping
of six protons and so,
we can say that there are six protons that are pumped
for every molecule of
FADH two.
Alright, so, here's a good place to pause and kind of
get to back to our original question, which was
we have this kind of range of ATP molecules
produced per molecule of NADH or FADH two
and why is it that, you know, we don't have a whole number
integer ratio between the amount of ATP and NADH
that we have.
And the reason kind of that we might be able to justify this
looking at our diagram here
is that NADH and FADH two each contribute
to this proton gradient but really,
it's not NADH or FADH two that's directly donating
anything to form ATP because remember,
that it's this proton gradient that forms
this intermembrane space here
that essentially fuels this ATP synthase,
remember that protons flow back through
this ATP synthase molecule and in doing so,
they essentially power
this pump to phosphorylate ADP into ATP.
And so, of course, maybe the question
we should really be asking is how many protons
does it take, or how many protons
need to flow through this ATP synthase
to phosphorylate one molecule of ADP into ATP,
and so, I'm actually gonna go ahead
back to our ratios up here and write up here
that if we knew
how many protons were necessary to produce
one molecule of ATP,
we would be able to calculate
essentially the ratio of ATP
to NADH
or FADH two.
And it's this calculation that I think
researchers are actually still trying to,
you know, nail down and, you know,
I'm sure depending on the type of cell
and the state of the cells,
the efficiency of this process is going to be
different and might, you know, change moment to moment
and so, maybe the expectation to have an exact number is
not realistic,
but researchers are pretty confident
with the number, right now, currently
of four protons
being necessary to produce one molecule of ATP,
so, I'm gonna go ahead and just write that in here.
And with this number, we can actually go ahead
and calculate the ratio of ATP to NADH
and so, simply, we have here
for every molecule of NADH,
we have two point five molecules of ATP.
And for every molecule of FADH, we have six divided by four,
where one point five molecules of ATP
that are produced.
So, remember, that even though it's kind of funky
that we're talking about kind of two and a half ATP
per molecule of NADH or per molecule of FADH two,
really, what this is alluding to
is the role of this chemi-osmotic coupling,
or using the proton gradient to fuel to ATP synthase
and because we're talking about protons now,
we need to factor in that,
we end up getting these non whole number
ratios between ATP and NADH or FADH two.
But with these ratios in mind, I actually wanna go ahead
and calculate kinda the sum total of ATP
that we produce in cellular respiration,
so I've already gone ahead and kinda created a table here,
and remember that we're talking about
one cycle of cellular respiration,
so, as a total ATP yield,
let's say per
one molecule of glucose, remember.
And so, I've already kind of written out here
how many ATP and electron carrier molecules
are produced in glycolysis and
the oxidation of pyruvate,
and the Krebs and TCA cycles, well, now, let's go ahead
and using our ratios here,
let's go ahead and write out how much ATP we have,
so two ATP is two ATP and two NADH,
using our conversion factors, two times two point five,
which is going to be five ATP.
And then we have again, five ATP
and two ATP here,
forming substrate level phosphorylation is two ATP.
And six NADH times two point five is
going to yield 15.
And two FADH two times one point five
is going to yield three.
And so, if we add all of this up,
we get 32 ATP.
Now, before I call it good,
I wanna make one more last nitpicky point
which is to realize that glycolysis, remember,
takes place in the cytosol,
so unlike the oxidation of pyruvate and the Krebs cycle,
which take place in the mitochondria,
the NADH that's produced in the glycolysis
must actually be shuttled somehow
into the inner mitochondrial membrane
in order to donate its electrons
into the electron transport chain.
But for some reason, it turns out that
the inner mitochondrial membrane is actually not permeable
to this molecule NADH.
So, the body has actually come up with something called
shuttle transport systems to shuttle this NADH
into the mitochondria.
And it turns out that depending on where the NADH
is shuttled into the electron transport chain,
so if we actually go back to our diagram here,
some of the electrons from the NADH
produced in glycolysis can be shuttled into
the first electron, first protein complex,
and some of them are actually shuttled into this
third protein complex here.
And so, depending on whether it's, you know,
shuttled earlier later on in the electron transport chain,
a different number of protons will be pumped
into the proton gradient, remember.
And so, the conversion factor
for the amount of ATP produced is gonna be different
depending on which shuttle is used.
So, I just wanna make that point
and have you be aware of the fact
that this number right here,
this number here is actually a range,
it can actually range from anywhere to three to five
ATP produced per molecule of NADH.
I'm gonna go ahead and kinda just adjust this
to say that really the range here is
30 to 32 ATP produced
per one cycle of cellular respiration,
and this right here is the generally accepted number
for the amount of ATP
produced in one cycle of cellular respiration.