Hemoglobin

Hemoglobin and its role in the circulatory system

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.