-: Alright, now we're going to look at some of the mechanics
of how we actually are making energy within the cell.
We talked about the organelles
and the parts that we're using.
So this is really going to focus on
kind of stuff that's happening around the mitochondria.
So we have these thing called ATP,
which is a three part molecule.
It's adenosine triphosphate, meaning three phosphates
attached to an adenosine molecule.
And that's basically the fuel source
for all cellular function.
So we need that to do anything in the cell
that requires energy, basically.
We can't use carbohydrates, fats,
or protein directly for the most part.
We mainly use ATP.
There's a few chemical reactions that can use other things.
But really our main fuel source, right, is the ATP.
I mean, that is the gasoline that you put in your car.
Your car may also need oil and transmission fluid
or whatever, but the gas is what makes it go.
That's what the ATP is here.
So all our macros are used by the mitochondria
to make ATP in some way, shape, or form.
Energy metabolism of the cell is going to be determined
by the ability to turn that fuel source, to turn carbs,
fats, protein, amino acids if needed into that ATP.
So it's my ability, how well can I do that?
How efficient can I do that?
At what rate can I do that?
How long can do I that before I start to build up
a lot of fatigue factors are all
going to affect the energy status
and the energy capabilities of that cell
and therefore what functions it can carry out.
So let's look at this whole ATP thing.
And let's talk about how that basically functions.
So we have our ATP.
And the way that actually gives us energy
is by releasing a phosphate.
So when we look at bonds between molecules or atoms,
there's a certain magnetic or energy basically
that's holding those things together.
And when those get broken, there is a release of energy.
And without control,
that energy is actually usually released as heat.
So that's what the whole term thermogenesis is,
when things break down they release heat.
So like, when you have a fire, right?
All that heat is coming from those bonds being broken.
So all of that carbon is being broken down
to the point where it actually is so broken down
that it dissipates into the air as like CO2 and whatnot.
So in this case,
what we do actually is we harness that energy.
Instead of letting it get released as heat,
we use it to fuel basically some sort of like
mechanical interaction with our body.
We harness that energy.
So when those bonds break, the parts of our cell
can actually harness that energy
and use it to do something on a biochemical basis.
So we've got ATP.
It will break down one of those phosphates, it falls off,
we get the energy from that release,
that break of those bonds, and we're left with ADP
which is adenosine diphosphate.
So now of the three phosphates, we're left with two.
One has now been taken off
and is kind of floating around by itself.
Then in order to be able to use that again,
we have to have the ability to take and put a phosphate
back onto the ADP to once again have ATP.
What we use our macronutrients for,
what use the glucose for, what we use the fatty acids for,
is to fuel the process in which we take the phosphate
and add it back to the ADP.
So this gives our cells the energy.
We use food to be able to recycle
the ADP back into ATP.
So we don't directly use our food for energy,
we use our food in order to recycle
the energy product that we have.
So if we look at the other side of the equation,
how do we actually consume?
What things actually are breaking down that ATP or requiring
ATP to be breaking down in order to do their function?
For us, we're mainly going to be focused on muscle
contraction 'cause we're concerned about energy in training.
So that's going to be a huge consumption of ATP
is actually going to be the muscle contractions.
Then everything else, so the nucleus's stuff, right?
So the reading and transferring of DNA and RNA.
Well, that costs energy as well.
Synthesizing proteins.
The ribosome requires energy.
Transporting those amino acids requires energy.
Supporting enzymatic reactions.
So all of our biochemical reactions
in some way, shape, or form usually require
some specific substrate or at some point in time
they also will require ATP to fuel that process.
ATP, when we break those bonds,
provides such a big source of energy,
it can be like a chain reaction that allows
other biochemical reactions to occur after the fact.
Almost like a domino effect.
It's like a big domino falling and able to knock over
a lot of smaller dominoes is what happens when we use ATP
'cause it can start a cascade where other reactions
that don't need quite as big a push
can happen subsequently because we've got this huge surge
of energy from breaking down that ATP.
Our fuel sources, we've been over these.
Glucose, fatty acids, amino acids.
The ketones are also on there.
Remember ketones, the easiest way to think of them
is they are essentially pre-broken down fat.
That's not like completely biochemically accurate.
But from a logistics perspective, that's what it is.
It's like fat that's been broken down
so that it can get to places easier and faster.
So it's transported differently
and it's able to skip some of the processes
that we need to get fat to ATP.
So the ketones can do it faster
which allows us to need less glucose for fuel.
When we look at all of those, it doesn't matter,
they're all going to go to the
mitochondria in some way, shape, or form.
We have fatty acids.
When we look at how those are going to be delivered,
we have fatty acids in the blood.
So the blood carries around fatty acids and triglycerides.
So it's like basically three fatty acids
attached to a glycerol molecule.
What I'll need to do then is actually break up
that triglyceride molecule into the individual fatty acids
to be able to actually use it.
So I get blood triglycerides.
So I eat food and usually that fat
is stored as triglyceride in the food.
And then I break that down, the liver will sometimes
break things down and re-synthesize the triglycerides,
send it into the bloodstream so it can be transported.
And then that can either go to the adipocytes,
the fat cells to be stored, or it can be sent out
to the cells which then will actually need to take that
triglyceride, break it down into the individual fatty acids.
And then each of those individual fatty acids,
which is essentially a chain of carbons,
has to be diced down into small pieces
and fed to the internal parts of the mitochondria
to actually be able to function.
We'll look at that in detail when
we look at mitochondrial respiration.
In terms of glucose,
obviously we have dietary sources of glucose.
We have glycogen stored in the muscles, stored in the liver.
That's all somehow going to get into the blood.
So if I'm just eating it, it may go straight into the blood.
Otherwise, it's got to come from glycogen from somewhere.
So if it goes into the blood,
it's going to mostly be coming from the liver.
But my muscles can use local glycogen.
So I have the ingestion, the liver,
or the other way I can get glucose in the blood,
remember, is the gluconeogenesis
which is actually using protein to make carbohydrates.
And that occurs in the liver.
But that's another way of getting glucose into the blood
that could then be sent out to
make ATP in other parts of the body.
Just because we have a fuel source
does not mean we're able to turn it into ATP.
When we look at how the mitochondria functions,
what you're going to see is that in order to do this,
we need specific vitamins and minerals
and we need certain cellular conditions
in order to get the macronutrients into the cell.
And then we need certain nutrients
in order to be able to actually break them down
to the point where they can enter the mitochondria.
And then the mitochondria itself has certain nutrients
that it needs to do its process
of taking that glucose or that fatty acid
and actually making ATP from it.
So don't assume that just because you give food,
you have food coming in, that your cells have energy.
You can have an excess of calories in the diet
and very poor energy at a cellular level.
You can be getting very little ATP made
even though you're taking a lot of food
because you're not efficient or you're missing
some key points and you have a lot of bottlenecks
in terms of getting macronutrients converted over into ATP.
So don't assume that because you have glucose
or because you have fatty acids in the diet
or that they're available in some way, shape, or form
that you are able to efficiently move those things
over and convert them into energy.
When we look at skeletal muscle,
in terms of actually getting glucose into them,
we have GLUT4 transporters which are the transporters that
are going to be up-regulated under two major conditions.
One is when we're training and exercising that muscle
and the other is in response to insulin.
And so what GLUT4 transporters do,
and we'll kind of look at an illustration here in the slide,
is they sit inside the cell and then they
move to the membrane when they are needed.
So they are only around when the
cell needs glucose coming in.
We have other GLUT transporters, GLUT1 and GLUT3.
And they mostly, at least in some ratio,
will sit in the membrane at all times.
So they're not prevalent in muscle tissue.
There are certain tissues that basically need
like a slow drip of glucose to feed them
and so they will have some of these.
But as we get into the advanced modules
in the continued education portion,
we will talk a lot more about these in detail
and conditions that could up-regulate or down-regulate
these two types of receptors.
We're going to focus mainly on the GLUT4 one
in this particular course and certification
because it is the one that is affected mostly by training
and the energy status of the cell.
If we look at insulin, insulin will come
and it will bind to an insulin receptor.
And then what we have is we have this
cascade of events that it goes through, right?
You don't need to memorize all of these things,
but it's important to know that there's a variety
of cytokines which are essentially like chemical messengers
that allow this whole chain reaction to happen
where we get insulin coming in
and eventually, through all of these reactions,
we get the stimulation of these GLUT4,
these green things, to go up into the membrane.
Once this is in the membrane, so this would be blood up here
and this would be the cell here,
once the GLUT4 is here, the glucose can go through.
When it's just sitting in here, the glucose can't come in.
It's got to get there.
So insulin's main job is to signal this
translocation of the GLUT4 to here.
What I want you guys to note, just as like a prequel
to everything that's going to come up,
is there's a lot of steps.
So you can imagine if any of these things were broken
or inhibited for one reason or another,
and the body's going to have a lot
of reasons to shut those things off, guess what?
Insulin is going to come and the GLUT4
is not going to get translocated.
What's that sound like?
Does that sound like insulin resistance to you guys?
That's because that's a big factor
is one of these internal mechanisms.
So insulin is doing its job.
We're getting it on the receptor.
There's this misconception that like,
insulin just bounces off the receptor
when it's not working and that's not what happens.
Insulin gets there, it does its job.
The cells aren't listening.
Remember, control is conditional.
Listening to these hormones is conditional
on all of these things in that cell
functioning like they're supposed to.
And there's going to be micronutrients
and cellular conditions that are responsible
for this happening and the rate and how easy it happens.
This also isn't a black and white thing.
So imagine when I have five insulin receptors up here
and in here all of these things, you know,
we'll say a couple of them are kind of in an eh,
I'm not sure I want to do this.
If there's one insulin bound to one
of those five receptors, nothing may happen.
If all five are filled up, that may be enough for insulin
to win the argument with whatever is going on
in here to get the GLUT4 here.
And that's one of the ways we get into this tug of war thing
between the systemic signal that is insulin
and this internal want of the cell saying hey,
let's block this Akt thing here because we have too much
oxidative stress or something else going on.
Well it's not like a light switch.
It's not on and off.
It's like an influence.
It's like having your two friends,
one says do this, the other one says do that.
You're going eh, which do I do, which do I do?
Eventually, one is going to influence over the other
because you're going to have to choose one way or another.
But it's this gray area where it's like, okay,
maybe a couple of these are going to go get translocated
but not as many as normally would happen.
And so what's the body going to do?
It's going to say if blood sugar
is still high, send more insulin.
Yell louder.
And then it depends who is going to win that argument.
And that's where that tug of war starts to happen.
We'll look at ATP production.
From a glucose perspective, we're going to have glycolysis
which is the breakdown of glucose
into its small enough parts that we can
actually fuel the ATP recycling.
Some of that happens in the cytosol.
So that fluid outside the nucleus,
outside of our other organelles.
So just that fluid area.
There's going to be part of that happening out there.
But once that initial reaction happens, we call this like
sometimes it's referred to as the investment phase.
So there's going to be a glucose broken down partly
in the cytosol but then that product
is going to go into the mitochondria.
And that's where we're going to
have mitochondrial respiration.
So glucose is going to go to pyruvate.
And then from here on,
this all happens within the mitochondria.
Fatty acids are going to enter the mitochondria
and this whole process here is going
to happen inside the mitochondria.
So if we look at these steps, what you're going to see is
the end pieces are all the same.
So they both go to this thing called acetyl-CoA.
And that is essentially the small pieces
of carbon that the fatty acids and the glucose
are ultimately going to be broken up to.
So when I said ketones are like very close to broken up
fatty acids, is the ketones essentially are one step away
from getting to this acetyl-CoA.
Where you may have, say you have like a 16-chain fatty acid.
Well that's going to give you essentially
like 16 acetyl-CoAs.
After that, this TCA thing.
That's the citric acid cycle.
We're going to look at that in detail.
And then the ETC on here stands
for the electron transport chain.
So if you want to come back to this slide
after we've talked about those,
that's just kind of what those short terms are.
The glycolysis that occurs in the cytosol,
so this is outside of the mitochondria.
We have this glucose.
And the important thing to get from here
is that, one, we're going to actually get
a little ATP outside of the mitochondria.
So this is like the only time that that happens.
Glucose will actually make us some ATP
without the mitochondria being involved.
And that happens in the cytosol through
this first part of glycolysis.
The other part that I want you to look at
is there is this thing called NAD.
And that is going to be a substrate that's used
in the cytosol but also by the mitochondria itself.
Actually, the mitochondria is going to focus
on using this product over here.
It's going to be very important when we get into the
metabolic phase is understanding outside here,
we're getting some energy
but we're also using this NAD thing.
From that, we're going to get two
of this pyruvic acid which is pyruvate.
So we went one glucose to two pyruvate.
We get a little ATP and we use some of this NAD thing.
Put that in your pocket because we're
going to talk about that in detail later.
You don't have to write that down
like in your notes in detail, but I just want you
to understand that there's going to be some significance
to what's happening outside of the mitochondria
versus what's happening inside of the mitochondria
when we talk about metabolic training.