I've talked a lot about the importance of hemoglobin in
our red blood cells so I thought I would dedicate an
entire video to hemoglobin.
One-- because it's important, but also it explains a lot
about how the hemoglobin-- or the red blood cells, depending
on what level you want to operate-- know, and I have to
use know in quotes.
These aren't sentient beings, but how do they know when to
pick up the oxygen and when to drop off the oxygen?
So this right here, this is actually a picture of a
hemoglobin protein.
It's made up of four amino acid chains.
That's one of them.
Those are the other two.
We're not going to go into the detail of that, but these look
like little curly ribbons.
If you imagine them, they're a bunch of molecules and amino
acids and then they're curled around like that.
So this on some level describes its shape.
And in each of those groups or in each of those chains, you
have a heme group here in green.
That's where you get the hem in hemoglobin from.
You have four heme groups and the globins are essentially
describing the rest of it-- the protein structures, the
four peptide chains
Now, this heme group-- this is pretty interesting.
It actually is a porphyrin structure.
And if you watch the video on chlorophyll, you'd remember a
porphyrin structure, but at the very center of it, in
chlorophyll, we had a magnesium ion, but at the very
center of hemoglobin, we have an iron ion and this is where
the oxygen binds.
So on this hemoglobin, you have four major binding sites
for oxygen.
You have right there, maybe right there, a little bit
behind, right there, and right there.
Now why is hemoglobin-- oxygen will bind very well here, but
hemoglobin has a several properties that one, make it
really good at binding oxygen and then also really good at
dumping oxygen when it needs to dump oxygen.
So it exhibits something called cooperative binding.
And this is just the principle that once it binds to one
oxygen molecule-- let's say one oxygen molecule binds
right there-- it changes the shape in such a way that the
other sites are more likely to bind oxygen.
So it just makes it-- one binding makes the other
bindings more likely.
Now you say, OK, that's fine.
That makes it a very good oxygen acceptor, when it's
traveling through the pulmonary capillaries and
oxygen is diffusing from the alveoli.
That makes it really good at picking up the oxygen, but how
does it know when to dump the oxygen?
This is an interesting question.
It doesn't have eyes or some type of GPS system that says,
this guy's running right now and so he's generating a lot
of carbon dioxide right now in these capillaries and he needs
a lot of oxygen in these capillaries surrounding his
quadriceps.
I need to deliver oxygen.
It doesn't know it's in the quadraceps.
How does the hemoglobin know to let go of the oxygen there?
And that's a byproduct of what we call allosteric inhibition,
which is a very fancy word, but the concept's actually
pretty straightforward.
When you talk about allosteric anything-- it's often using
the context of enzymes-- you're talking about the idea
that things bind to other parts.
Allo means other.
So you're binding to other parts of the protein or the
enzyme-- and enzymes are just proteins-- and it affects the
ability of the protein or the enzyme to do
what it normally does.
So hemoglobin is allosterically inhibited by
carbon dioxide and by protons.
So carbon dioxide can bond to other parts of the
hemoglobin-- I don't know the exact
spots-- and so can protons.
So remember, acidity just means a high
concentration of protons.
So if you're in an acidic environment, protons can bond.
Maybe I'll do the protons in this pink color.
Protons-- which are just hydrogen without electrons,
right-- protons can bond to certain parts of our protein
and it makes it harder for them to hold onto the oxygen.
So when you're in the presence of a lot of carbon dioxide or
an acidic environment, this thing is going to let go of
its oxygen.
And it just happens to be that that's a really good time to
let go of your oxygen.
Let's go back to this guy running.
There's a lot of activity in these cells right here in his
quadriceps.
They're releasing a lot of carbon dioxide into the
capillaries.
At that point, they're going from arteries into veins and
they need a lot of oxygen, which is a great time for the
hemoglobin to dump their oxygen.
So it's really good that hemoglobin is allosterically
inhibited by carbon dioxide.
Carbon dioxide joins on certain parts of it.
It starts letting go of its oxygen, that's exactly where
in the body the oxygen is needed.
Now you're saying, wait.
What about this acidic environment?
How does this come into play?
Well, it turns out that most of the carbon dioxide is
actually disassociated.
It actually disassociates.
It does go into the plasma, but it actually gets turned
into carbonic acid.
So I'll just write a little formula right here.
So if you have some CO2 and you mix it with the water-- I
mean, most of our blood, the plasma-- it's water.
So you take some carbon dioxide, you mix it with
water, and you have it in the presence of an enzyme-- and
this enzyme exists in red blood cells.
It's called carbonic anhydrase.
A reaction will occur-- essentially you'll end up with
carbonic acid.
We have H2CO3.
It's all balanced.
We have three oxygens, two hydrogens, one carbon.
It's called carbonic acid because it gives away hydrogen
protons very easily.
Acids disassociate into their conjugate base and hydrogen
protons very easily.
So carbonic acid disassociates very easily.
It's an acid, although I'll write in some type of an
equilibrium right there.
If any of this notation really confuses you or you want more
detail on it, watch some of the chemistry videos on acid
disassociation and equilibrium reactions and all of that, but
it essentially can give away one of these hydrogens, but
just the proton and it keeps the electron of that hydrogen
so you're left with a hydrogen proton plus-- well, you gave
away one of the hydrogens so you just have one hydrogen.
This is actually a bicarbonate ion.
But it only gave away the proton, kept the electron so
you have a minus sign.
So all of the charge adds up to neutral and that's neutral
over there.
So if I'm in a capillary of the leg-- let me see
if I can draw this.
So let's say I'm in the capillary of my leg.
Let me do a neutral color.
So this is a capillary of my leg.
I've zoomed in just one part of the capillary.
It's always branching off.
And over here, I have a bunch of muscle cells right here
that are generating a lot of carbon dioxide
and they need oxygen.
Well, what's going to happen?
Well, I have my red blood cells flowing along.
It's actually interesting-- red blood cells-- their
diameter's 25% larger than the smallest capillaries.
So essentially they get squeezed as they go through
the small capillaries, which a lot of people believe helps
them release their contents and maybe some of the oxygen
that they have in them.
So you have a red blood cell that's coming in here.
It's being squeezed through this capillary right here.
It has a bunch of hemoglobin-- and when I say a bunch, you
might as well know right now, each red blood cell has 270
million hemoglobin proteins.
And if you total up the hemoglobin in the entire body,
it's huge because we have 20 to 30
trillion red blood cells.
And each of those 20 to 30 trillion red blood cells have
270 million hemoglobin proteins in them.
So we have a lot of hemoglobin.
So anyway, that was a little bit of a-- so actually, red
blood cells make up roughly 25% of all of the
cells in our body.
We have about 100 trillion or a little bit
more, give or take.
I've never sat down and counted them.
But anyway, we have 270 million hemoglobin particles
or proteins in each red blood cell-- explains why the red
blood cells had to shed their nucleuses to make space for
all those hemoglobins.
They're carrying oxygen.
So right here we're dealing with-- this
is an artery, right?
It's coming from the heart.
The red blood cell is going in that direction and then it's
going to shed its oxygen and then it's
going to become a vein.
Now what's going to happen is you have this carbon dioxide.
You have a high concentration of carbon dioxide in the
muscle cell.
It eventually, just by diffusion gradient, ends up--
let me do that same color-- ends up in the blood plasma
just like that and some of it can make its way across the
membrane into the actual red blood cell.
In the red blood cell, you have this carbonic anhydrase
which makes the carbon dioxide disassociate into-- or
essentially become carbonic acid, which
then can release protons.
Well, those protons, we just learned, can allosterically
inhibit the uptake of oxygen by hemoglobin.
So those protons start bonding to different parts and even
the carbon dioxide that hasn't been reacted with-- that can
also allosterically inhibit the hemoglobin.
So it also bonds to other parts.
And that changes the shape of the hemoglobin protein just
enough that it can't hold onto its oxygens that well and it
starts letting go.
And just as we said we had cooperative binding, the more
oxygens you have on, the better it is at accepting
more-- the opposite happens.
When you start letting go of oxygen, it becomes harder to
retain the other ones.
So then all of the oxygens let go.
So this, at least in my mind, it's a brilliant, brilliant
mechanism because the oxygen gets let go just where it
needs to let go.
It doesn't just say, I've left an artery and
I'm now in a vein.
Maybe I've gone through some capillaries right here and I'm
going to go back to a vein.
Let me release my oxygen-- because then it would just
release the oxygen willy-nilly throughout the body.
This system, by being allosterically inhibited by
carbon dioxide and an acidic environment, it allows it to
release it where it is most needed, where there's the most
carbon dioxide, where respiration is occurring most
vigorously.
So it's a fascinating, fascinating scheme.
And just to get a better understanding of it, right
here I have this little chart right here that shows the
oxygen uptake by hemoglobin or how saturated it can be.
And you might see this in maybe your biology class so
it's a good thing to understand.
So right here, we have on the x-axis or the horizontal axis,
we have the partial pressure of oxygen.
And if you watched the chemistry lectures on partial
pressure, you know that partial pressure just means,
how frequently are you being bumped into by oxygen?
Pressure is generated by gases or molecules bumping into you.
It doesn't have to be gas, but just molecules
bumping into you.
And then the partial pressure of oxygen is the amount of
that that's generated by oxygen molecules
bumping into you.
So you can imagine as you go to the right, there's just
more and more oxygen around so you're going to get more and
more bumped into by oxygen.
So this is just essentially saying, how much oxygen is
around as you go to the right axis?
And then the vertical axis tells you, how saturated are
your hemoglobin molecules?
This 100% would mean all of the heme groups on all of the
hemoglobin molecules or proteins have bound to oxygen.
Zero means that none have. So when you have an environment
with very little oxygen-- and this actually shows the
cooperative binding-- so let's say we're just dealing with an
environment with very little oxygen.
So once a little bit of oxygen binds, then it makes it even
more likely that more and more oxygen will bind.
As soon as a little-- that's why the slope is increasing.
I don't want to go into algebra and calculus here, but
as you see, we're kind of flattish, and
then the slope increases.
So as we bind to some oxygen, it makes it more likely that
we'll bind to more.
And at some point, it's hard for oxygens to bump just right
into the right hemoglobin molecules, but you can see
that it kind of accelerates right around here.
Now, if we have an acidic environment that has a lot of
carbon dioxide so that the hemoglobin is allosterically
inhibited, it's not going to be as good at this.
So in an acidic environment, this curve for any level of
oxygen partial pressure or any amount of oxygen, we're going
to have less bound hemoglobin.
Let me do that in a different color.
So then the curve would look like this.
The saturation curve will look like this.
So this is an acidic environment.
Maybe there's some carbon dioxide right here.
So the hemoglobin is being allosterically inhibited so
it's more likely to dump the oxygen at this point.
So I don't know.
I don't know how exciting you found that, but I find it
brilliant because it really is the simplest way for these
things to dump their oxygen where needed.
No GPS needed, no robots needed to say, I'm now in the
quadriceps and the guy is running.
Let me dump my oxygen.
It just does it naturally because it's a more acidic
environment with more carbon dioxide.
It gets inhibited and then the oxygen gets dumped and ready
to use for respiration.