Leah here from leah4sci.com/MCAT and in this video we'll look at Hemoglobin Dissociation
Curve from a perspective on understanding for the standard curve and then the right
shift and the left shift.
In video one we introduced the concept of Hemoglobin and that Oxygen binding is cooperative
which we compare to peer pressure.
So let's take a look at what happens.
When you're graphing Hemoglobin Oxygen dissociation or Hemoglobin Oxygen Affinity you want your
Y-axis to represent the percent saturation.
The percentage of Hemoglobin molecules that are saturated meaning that are bound to Oxygen,
but keep in mind there are also a lot of free floating Oxygen that simply dissolve in a
blood.
For the X-axis, we're looking at the pressure of O2 which is measured in millimeters of
mercury.
When you're looking at the concentration of a gas you can look at it from the perspective
of pressure which is force over area so the more Oxygen or the more gas is dissolve, the
higher the pressure or you can look at it as a molarity.
But here the pressure is actually referring to the concentration coz we're looking at
how much Oxygen is dissolved to give us that pressure.
Hemoglobin naturally does not like Oxygen.
So if you're starting at a very low pressure of O2 starting with zero and you slowly dissolve
more Oxygen will slowly increase the pressure of O2.
You see a very slight increase in the percent saturation because Hemoglobin does not like
Oxygen especially in the T state but as the pressure increases, you'll start to get an
Oxygen molecule here and there that gets force into binding out of just sheer volume of Oxygen
molecules and suddenly Hemoglobin goes from not liking Oxygen to suddenly really wanting
Oxygen because of that peer pressure, because of that cooperativity.
And you see that with a very sharp increase on the curve as more and more and more Oxygen
is binding for every slight increase in pressure until you get to a point when most of the
Hemoglobin is full and even though you increase the concentration of Oxygen you can't really
fill anymore sites because there aren't anymore sites to fill.
And that's where you get that near plateau where it levels out and you'll see that increase
the concentration will cause a very slight increase but you don't see any significant
change.
If you wanna compare this to what you understand for enzyme activity just think of it as reaching
the Vmax where it doesn't matter if you increase the substrate you're at the maximum capacity
for that protein.
We're not looking at numbers here because we want to understand this logically, conceptually.
But I do want you to look at the halfway point.
If we look at the pressure that gives us a 50% saturation, meaning half of the hemoglobin
molecules are bound to Oxygen.
We call that the P50 and this is good way to understand the affinity for Oxygen at any
given concentration or any type of condition.
Instead of looking at the top or the bottom of the curve, just find that halfway saturation
point that P50 and then look at how that compares to another type of graph.
Is the shift to the right or is the shift to the left.
Notice that the shape of this curve is following the letter S, it kinda looks like an S because
it is a sigmoidal curve and this is the characteristic curve that you're going to see for a cooperative
binding.
This contrasts to a very similar molecule myoglobin.
Myoglobin follows a standard binding where at a low concentration it just starts to pick
up those Oxygen atoms and then it just plateaus as it gets to the top.
Myoglobin is a monomer, it just has one polypeptide chain.
Hemoglobin is a tetramer and the tetramer has four units that influence each other.
Myoglobin will easily pick up Oxygen at a low concentration but unlike Hemoglobin, it
won't let go unless the cells are desperate and starving for Oxygen and then it'd be grudgingly
let go of the Oxygen.
The Myoglobin curve is what you're used to seeing for a standard enzyme or protein and
notice that the shape is not sigmoidal.
It's simply starts out with a nice slope and then tapers off.
We mentioned that there are different molecules that will shift the Hemoglobin, Oxygen saturation
curve, some will shift if to the right and some will shift it to the left.
But a lot of students will hear this and memorize.
I don't want you to do that.
So what I want to do first is look at what happens when there's a right shift, what happens
when there's a left shift and what does means logically and once you understand it, it will
be much easier to understand why change in concentration CO2 shifts in one direction,
a low concentration of H+ scion shifted in the other direction.
We'll start by analyzing a right shift.
A right shift means that the curve is going to shift over completely to the right.
So we start out at the same zero because when there is no Oxygen, there's no binding.
But now, the curve is going to go slightly towards the right and that means that rise
used to seeing shows up more to the right on the graph and eventually it too will reach
that asymptote . What does it mean when it shifted to the right?
Let's take a look at the P50 value.
The P50 is still at that same location but for this right shifted graph, it takes a much
higher concentration of O2 to reach 50 percent saturation.
And what this is telling you is that if hemoglobin is less willing to accept Oxygen, you have
to put in so much more Oxygen for it to finally accept the Oxygen enough to reach a 50 percent
saturation.
So a right shift represents a lower Oxygen affinity.
If we look at that same graph and now we want to see what it looks like when the O2 concentration
is the same that previously gave us the P50, look at that difference.
We have a much much lower percent saturation for an Oxygen concentration that previously
gave us 50 percent saturation.
When the graph shifts to the right you have a much lower affinity for Oxygen and hemoglobin
is in a state where it wants to let go of Oxygen rather than pick up new Oxygen.
Now what happens if I take the same hemoglobin curve but I shift it to the left?
Once again we'll start out at that same zero point but this time we're going to see the
increase happening much earlier on the graph.
It's more of the left compared to the initial graph because it's left shifted.
And here we see the increase in binding and eventually we reach that same asymptote.
Once again let's analyze what happened.
If you look at the P50, you'll notice that it happens at a much much much lower concentration
of Oxygen compared to a standard hemoglobin curve and that means with just a slight increase
in concentration the hemoglobin that is left shifted is picking up so much Oxygen, the
affinity for Oxygen is so much higher.
And if we look at the same left shift curve and we want to see what it looks like when
that Oxygen concentration is the same as what previously gave as a P50 for our standard
hemoglobin, we're nearly at the top.
This hemoglobin is nearly maxed out and it's reaching that full hemoglobin saturation,
meaning it's carrying as much Oxygen as it can because it has such a high affinity for
Oxygen.
So now the question is, when do we see a standard curve?
When does it shift to the right and when does it shift to the left?
And the answer is, that it's constantly changing.
The hemoglobin curve is dynamic and that's how you want it to be for the survival of
an organism.
You want hemoglobin to go to the lungs and have a very high Oxygen affinity so that it
grabs all the available Oxygen molecules before it leaves.
And as it leaves the lungs, you want the Oxygen affinity to decrease so that as the hemoglobin
travels through the bloodstream it starts to give away that Oxygen.
But even more so you wanna have a super low affinity when hemoglobin reaches actively
respiring cells.
If cells are actively metabolizing, they need a lot more Oxygen and you want to make sure
that, that is when hemoglobin knows to let go of as much as Oxygen as possible so that
these cells the Oxygen.
They need to carry out their metabolic processes.
What causes to shift through the right?
to have a lower affinity?
a right shift will be brought on by a high proton concentration, meaning a lower pH.
A high CO2 concentration and high temperature.
A left shift, meaning a greater affinity will be brought on by the exact opposite.
If we have a low proton concentration, low CO2, or high O2, right on the lungs we have
a lot of O2, lower temperature and an increase concentration in a molecule 23BPG also refer
to as DPG.
Be sure to join me in the next video where we start to break down the effect of each
individual component to understand how and why it causes to curve to shift to the right
or left.
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