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.