- [Instructor] In talking about how
oxidative
phosphorylation
is actually regulated inside of our cells,
I find it helpful to remind myself of two basic things
about this pathway.
So the first is,
what is the purpose of oxidative phosphorylation?
So remember,
this is a process that takes place
inside of the mitochondria
in the electron transport chain, right?
And it's sole purpose is to produce
lots of ATP.
So remember, ATP can be produced without oxygen,
through substrate-level phosphorylation
which does take place in glycolysis
and also the Krebs cycle,
but what's cool about electron transport chain
and oxidative phosphorylation is that
by having oxygen and having the electrons shuttled
through these electron carrier molecules
like NADH and FADH,
it allows the body to produce efficiently
a whole lot of ATP,
which is important for many of our tissues
which can't survive just on substrate-level phosphorylation.
For example, your brain and your heart,
and some other tissues in your body,
really rely on the electron transport chain
to produce most of it's ATP.
The second point that's important to recognize
is that oxidative phosphorylation
is the kind of common end pathway
of aerobic respiration.
What do I mean by this?
Remember that there are many different types of fuels
that can enter cellular respiration.
We've talked about glucose and also fatty acids
can enter cellular respiration
as well as occasionally, under extreme starvation,
amino acids can also enter,
but ultimately, all of these are broken down
and much of their reducing power
is stored in the electron carrier molecules
like NADH and FADH2 that are ultimately shuttled,
as I mentioned before,
to the electron transport chain to produce as ATP.
Alright.
So how do these two points relate back
to how oxidative phosphorylation is regulated?
Well this first point simply reminds me that the major form
of regulation in oxidative phosphorylation
is looking at the energy needs of the cells,
and the way that the body does this
is by looking at the levels of ADP
compared to the levels of ATP.
You know, specifically, it should make sense to you
that if the body has a lot ATP lying around,
it should essentially be a sign to say,
you know what?
We have enough energy.
We don't need to produce more.
oxidative phosphorylation can slow down.
But on the other hand,
if we have a lot of ADP compared to ATP,
it's a sign that the cell is running out of ATP,
and that more ADP can be and should be phosphorylated
using the electron transport chain.
This is actually just really a kind of application
of Le Chatelier's Principle,
which is a general chemistry principle
to oxidative phosphorylation
and I will actually go into a little bit more detail
about this in a second, but first,
I wanna kind of touch on a second point here,
which is that it's a common end pathway
for aerobic respiration.
And I really make this point because it reminds me
why there is kind of no major hormonal
or allosteric,
remember allosteric means
there is some type of enzymatic control
that's being altered,
but there is no major hormonal or allosteric
regulation in oxidative phosphorylation.
The way I've kind of always justified that to myself
is that these are very,
these forms of regulations allow us
to really fine tune regulation
and to make sure that when we turn something on,
we are turning it on with full certainty,
but the fact that it's downstream
of many of the entry points to aerobic respiration,
such as breaking down glucose and glycolysis
and the oxidation of fatty acids,
means that it's probably more important for those pathways,
which they in fact do have
a lot of hormonal and allosteric regulation,
but once those pathways are turned on,
it's kind of just gonna keep rolling down the pathway
and it probably may not be as important to have that level
of fine-tuning in oxidative phosphorylation.
So with that in mind,
let's go ahead and talk about more about
how the energy levels in the body
are used to regulate oxidative phosphorylation.
I've gone ahead and drawn out a simplified diagram
of the electron transport chain
and I want to remind you
that it's much more complex than this, right?
We know we have four protein complexes.
We have ATP synthase.
We have this all occurring
in the inner mitochondrial membrane,
but for our purposes,
I just really wanted to highlight what the main reactants
and products of the electron transport chain were.
Let me go ahead and guide you through this.
We have the entry of electron carrier molecules
such as NADH, and remember,
we can also be dealing with FADH too as well,
but just as an example, I'm using NADH.
the NADH carries two electron from the molecule,
from the fuel such as glucose
or it could be fatty acid or some type of fuel,
and it essentially gets oxidized
at the electron transport chain.
It releases it's electrons
into the electron transport chain
and becomes itself oxidized.
This flow of electrons, of course,
fuels the phosphorylation of ADP
and a free phosphate group into ATP.
Of course this is all done indirectly
through a proton gradient
that's formed in the intermitochondrial membrane.
Then finally,
the electrons must have somewhere to go
and they end up reducing oxygen.
It's kind of funky to think about two electrons
reducing half an oxygen
but this is just so that the stoichiometry works out.
You can see here that if we were to reduce
one molecule of oxygen of course,
we'd need four electrons but in any case,
it reduces oxygen and it combines with some free protons
to produce some water.
At this point,
I want to remind you of Le Chatelier's Principle
in general chemistry which states
that if you have an equilibrium,
so let's say this overall reaction
of the electron transport chain
is our chemical reaction that's in equilibrium,
and there is some type of alteration to this equilibrium,
so let's say we have the addition of more reactant
or we take away some product,
Le Chatelier's Principle essentially says
that the equilibrium will re-equilibrate
to counter this change.
So it turns out,
that this is exactly how the electron transport chain
is regulated.
To make this point,
let's go ahead and basically ask ourselves
what would happen if we had more NADH,
more ATP, more free phosphate, or more oxygen around.
Remember these are all of our reactants.
Indeed, if we had more of these reactants,
Le Chatelier's Principle would essentially say that
this reaction, so to say, would be pushed
towards the forward direction and we would produce more ATP.
We would say that that kind of flow of electrons
through the electron chain is faster
and we'd get more ATP.
Now, of all three of these reactants,
I just want to make a point here
that practically speaking,
we consider the level of oxygen to be pretty constant.
If we're breathing in and out normally,
normally this is not a limiting factor
that essentially alerts the electron transport chain
to go faster.
I'm just gonna go ahead and erase that
for practical purposes.
But generally speaking, of these three,
the NADH, the ADP, and the free phosphate group,
it's really the levels of ADP in a cell
that are most likely to alert the electron transport chain
to produce more ATP.
That's just because it's usually
the limiting factor of all three.
But it should make sense to you that high levels of NADH
are essentially assigned from up above
from the breakdown of glucose or fatty acids
that it's time to make more energy for the cell.
Of course, we can also use that experiment
for the products of the reaction.
Specifically, let's say we had elevated levels
of ATP in a cell or elevated levels
of the oxidized form of these electron carrier molecules.
Le Chatelier's Principle would tell us
that this equilibrium would essentially shift
in the opposite direction,
so the flow of electrons through would be slower
and we would produce less ATP.
Of course, you know in reality,
we don't really think about electrons traveling
the opposite direction down the electron transport chain,
but this is just a way to kind of essentially signify
that having higher levels of ATP in the body,
or you know, high levels of NAD+,
are essentially, by Le Chatelier's Principle,
putting a break on the electron transport chain.
Just as before,
the ADP levels were more likely to alert the
electron transport chain.
ATP levels are kind of the limiting factor
to alert the electron transport chain
as compared to the NAD+ levels.
That's really because the body usually keeps NAD+ and NADH
in a pretty kind of stable ratio.
The body's really looking to whether
there's high levels of ADP or ATP
to ultimately decide and regulate
how fast the electron transport chain is.