Hemoglobin Cooperativity - Online Tutor, Practice Problems & Exam Prep

Hemoglobin exhibits positive cooperativity, allowing it to bind oxygen more efficiently, resulting in a sigmoidal oxygen binding curve. This cooperativity contrasts with myoglobin, which binds oxygen tightly but does not release it effectively due to its high affinity. Hemoglobin's ability to optimize oxygen delivery to tissues, especially under varying partial pressures, enhances its role as an oxygen transporter. Oxygen acts as a homotrophic allosteric activator, promoting further binding, which is crucial for efficient oxygen transport in the circulatory system.

Heme Cooperativity

In this video, we're going to talk about hemoglobin's positive cooperativity. And so of course, we already know from our last lesson video that hemoglobin displays positive cooperativity, and really, it's this positive cooperativity that allows hemoglobin's oxygen binding to display sigmoidal behavior, which of course just means that it's going to have an S-shaped curve on a saturation curve. And so if we take a look down below at our image, notice what we have is a saturation curve where we have the fractional saturation θ on the y-axis. And then on the x-axis, what we have is the concentration of ligand or the concentration of oxygen gas. And so notice that hemoglobin's curve is here in red, and hemoglobin is actually displaying sigmoidal behavior because it has this S-shaped curve. This is all due to hemoglobin's positive cooperativity.

And so recall from our previous lesson videos that positive cooperativity is just when the binding of a ligand molecule actually makes it easier for other ligand molecules to bind to the protein. In other words, what we can say is that positive cooperativity R state, which is the relaxed state, and the R state, which is the relaxed state and binds ligands more efficiently, allowing the ligands to bind easier to the protein. And so one thing that's important to note is that cooperativity, in general, actually requires multiple subunits. And so because myoglobin only has one single subunit, it does not have multiple subunits, and that means that it does not display cooperativity, and so myoglobin's oxygen binding curve is not going to be sigmoidal but instead will display a rectangular hyperbola.

And so if we take a look down below at myoglobin's oxygen binding curve, which is this black curve here, notice that it is not sigmoidal and instead it displays a rectangular hyperbola. This is all due to the fact that myoglobin has no cooperativity. And so in our next video, we'll be able to talk about the exact models that explain hemoglobin's positive cooperativity. So I'll see you guys in that video.

Heme Cooperativity

So recall that way back in our previous lesson videos, we had talked about two different models that can explain an allosteric protein's positive cooperativity and sigmoidal curvature. And those two different models were the concerted model as well as the sequential model. It turns out that hemoglobin's oxygen-binding behavior is actually best explained via a combination of both the concerted and the sequential models. We'll be able to talk more about this idea of how this is a combination of both of these models for hemoglobin later in our course when we discuss hemoglobin's Hill plot. But for now, what I want you to know is that moving forward, we're going to represent deoxygenated hemoglobin as just HB, and deoxygenated hemoglobin is going to be in the inactive tense T state which binds ligand or oxygen very inefficiently. We're also going to represent oxygenated hemoglobin as just HBO₂, even though we know that technically its chemical formula would be H(HBO₂)₄ when it's bound to all 4 oxygens. We're just going to represent it in a more simplified fashion, just for ease on the eyes. The oxygenated hemoglobin is going to be in the actively relaxed R state, which binds to ligand much more efficiently.

Over here on the left-hand side, we have a reminder of the concerted model as well as the sequential model as it applies to hemoglobin. Recall that with the concerted model, the hemoglobin protein is going to transition from its T state to its R state simultaneously in a concerted fashion where all of the subunits of Hemoglobin are going to simultaneously convert from the T state to the R state and vice versa. With the sequential model, hemoglobin's conversion from its T state to its R state is going to occur sequentially in each individual subunit, and the positive cooperativity is going to be displayed through these altered neighboring subunits, who get increased oxygen-binding affinity. Hemoglobin's positive cooperativity is directly being shown here, with this altered conformation with increased oxygen-binding affinity.

Over here on the right-hand side, we have a saturation curve, very similar to the ones that we had seen in our previous lesson videos, where we have the fractional saturation, which is either theta or y, on the y-axis. On the x-axis, we have the concentration of ligand or the concentration of oxygen gas. We have these three different curves here in our plot. The black curve here is a rectangular hyperbola, which we know represents no cooperativity. The blue curve and the red curve are very similar. However, notice that they're labeled differently. The blue curve represents hemoglobin if only the concerted model applied to hemoglobin. The red curve represents hemoglobin's actual binding curve. Hemoglobin's actual binding curve does not perfectly overlap with the concerted model only curve, which means that hemoglobin does not only display the concerted model. It actually does display some features of the sequential model. And of course, because hemoglobin's curve is so close to the concerted model, that is also suggesting that it must display some features of the concerted model as well. This plot is somewhat of evidence to show that hemoglobin's oxygen-binding behavior is explained through a combination of the concerted and sequential models. We'll be able to get some practice utilizing these ideas as we move forward in our course. So I'll see you guys in our next video.

Heme Cooperativity

In this video, we're going to talk about oxygen binding curves which are actually very similar to the previous saturation curves from our previous lesson videos. And so, really, the main difference between oxygen binding curves and the previous saturation curves from our previous lesson videos is the x-axis. And so oxygen binding curves will plot the fractional saturation, which is abbreviated really no change here on the y-axis. Really no change here on the y-axis. However, oxygen binding curves, instead of plotting the concentration of the ligand in units of molarity on the x-axis, it will actually plot the partial pressure of oxygen on the x-axis and the partial pressure of oxygen is abbreviated as just P O₂. And so we can see that down below that oxygen's partial pressure or P O₂ is being plotted on the x-axis. And so the reason that the partial pressure of oxygen is being plotted on the x-axis here is because oxygen, O₂, is actually a gas, and gases in science are typically measured using their partial pressures. And so the partial pressure of oxygen or the P O₂ is a completely standard way to be able to express the concentration of oxygen. Which again, when it's in this format like this, usually, the units are going to be in molarity. However, when it comes to the partial pressure of gases, the unit is going to be a unit of pressure and a unit of pressure, an example of a unit of pressure is the torr. And so what's important for you guys to know is that the partial pressure of oxygen is actually directly proportional to the concentration of oxygen gas. And so what this means is that the partial pressure of oxygen, we can really think of it in the same way that we think about the concentration of oxygen. And so, really all we're saying here is that moving forward we're going to be using the partial pressure of oxygen on the x-axis. And so taking a look at this curve, that we have here, this red curve, notice that we're showing hemoglobin's oxygen binding, which is showing sigmoidal behavior due to its positive cooperativity. And what I want you guys to note here is that the partial pressure of oxygen is actually going to dictate hemoglobin's oxygen affinity. And so at very low partial pressures, very far to the left, hemoglobin is mainly going to be in its T state, and the T state we know is the tense state and has a very low affinity for oxygen. And so this region that it's being pointed to down here is referring to hemoglobin when it has a very low affinity for oxygen. And then, of course, as we increase the partial pressure of oxygen from left to right on this x-axis, oxygen will begin to bind to hemoglobin and hemoglobin's cooperativity is coming into play. And so, what I want you guys to note is that ultimately, hemoglobin is going to reach a very high affinity state and that is when all of its subunits are going to be in the R state. And so, essentially what we're seeing is that increasing the partial pressure of oxygen is actually increasing hemoglobin's affinity for oxygen. And so what this means is that oxygen itself is acting as a homotropic allosteric activator, which recall from our previous lesson videos, homo just means the same, and so, homotropic is just referring to the fact that oxygen binding actually increases hemoglobin's ability to bind more oxygen. And so because oxygen is increasing, the binding of itself, it is going to be a homotropic allosteric effector. And so, the reason that it's activating is because it's actually increasing hemoglobin's oxygen affinity. And so really, this is what induces the positive cooperativity in hemoglobin's subunits, is the fact that oxygen acts as this allosteric activator. And so down below right here, we're just emphasizing this same exact idea right here by saying that oxygen is a homotropic allosteric activator, that essentially is going to promote additional binding of oxygen to hemoglobin. And again this is just reinforcing what we already knew about hemoglobins positive cooperativity. And so, this here concludes our introduction to Oxygen Binding Curves and I'll see you guys in our next video.

Heme Cooperativity

In this video, we're going to talk about how hemoglobin's positive cooperativity actually makes hemoglobin a much better oxygen transporter than myoglobin. And so recall from our previous lesson videos, we said that positive cooperativity as it relates to hemoglobin just means that the binding of oxygen to hemoglobin is going to stimulate hemoglobin to bind even more oxygen. And so really it's this positive cooperativity that allows hemoglobin to be a much better deliverer and transporter of oxygen to the tissues than its counterpart, myoglobin, specifically for two reasons. Reason number 1 is that myoglobin cannot transport oxygen to the tissue simply because it has such a low k_d. And, of course, we know from our previous lesson videos that a low k_d corresponds with a high oxygen affinity. And a high oxygen affinity, of course, means that myoglobin is going to have no problems binding to oxygen. However, myoglobin binds so well to oxygen even at low partial pressures of oxygen that it simply does not want to release oxygen when it gets to the tissues. And so myoglobin simply cannot be a transport of oxygen to the tissues because it would not release oxygen once it gets to the tissues. Now the second reason that hemoglobin is a much better delivery and transporter of oxygen to the tissues than myoglobin is because hemoglobin is an allosteric protein that displays the threshold effect, and this threshold effect in hemoglobin allows hemoglobin to optimize its oxygen release to the tissues. And so hemoglobin is able to release more oxygen to tissues that are working harder and depleting more oxygen so they have lower oxygen. And so, again, this means that hemoglobin can release more oxygen to these tissues that have and need more oxygen.

If we take a look at our oxygen binding curve down below, notice on the y-axis what we have is the fractional saturation theta or y. And then on the x-axis what we have is the partial pressure of oxygen. And notice that we have these two different curves. We've got this black rectangular hyperbolic curve for myoglobin and then we've got this red sigmoidal curve here for hemoglobin. And, of course, we have these light colored backgrounds to represent the partial pressure of oxygen in the lungs over here in light blue, which is right around about 100 tors. And then we've got this light green background for the partial pressure of oxygen in the tissues, which is ranging somewhere between 20 tors at its lowest to about 40 tors at its highest. And so what I want you guys to notice is that for this black curve here for myoglobin, its k_d, which corresponds with a fractional saturation of 0.5, is showing up at a very, very low value of about 2.8. And that's very, very low with respect to the k_d of hemoglobin, which is at 26. And so, essentially, a low k_d, we know means a high oxygen affinity. And so myoglobin's oxygen affinity is so high that it does not want to release oxygen once it gets to the tissues. And so we can see here that in the lungs, both hemoglobin and myoglobin's curve are very, very high in binding. The theta is really, really close to about 1. However, once we get to the tissues, we can see that myoglobins and hemoglobin curves are separating from each other. And so notice that myoglobin's curve even at the lowest partial pressures of oxygen in the tissues, is not really changing much from when it was in the lungs. And so, it's not really releasing that much oxygen at all when it's in the tissues making myoglobin a horrible oxygen transporter. However, hemoglobin on the other hand is showing this threshold effect here where it's able to essentially optimize its oxygen release to the tissues. And so, notice that tissues that have a higher partial pressure of oxygen, they do not need as much oxygen as tissues that have low oxygen. And so, notice that hemoglobin will release a smaller amount of oxygen to tissues that have higher partial pressures of oxygen. And then hemoglobin will release a lot more oxygen to tissues that have a much lower partial pressure of oxygen. And so, this is what allows hemoglobin to be the best in an excellent transporter and deliverer of oxygen

Notice over here on the right, what we're showing you is a little circulatory system here. And, of course, it's showing how blood is delivered and transported throughout our bodies. And so here in the center, of course, what we have is our hearts which act as a pump to pump the blood throughout our bodies. Now, at the top here, what we have is the blood as it relates to the lungs and so, here what we have is some information and notice that this information corresponds with what we're seeing over here in our plot. So the partial pressure of oxygen in the lungs is right around 100 tors. We can see that here in our plot. And notice that hemoglobin saturation in the lungs is right around 98%. So it's really really high here. And notice that myoglobin saturation in the lungs is really similar. It's also 99%, which is really close to 98%. So, really, they're binding in the lungs. It's pretty much the same. However, notice that it, the binding is much different between hemoglobin and myoglobin when it comes to the tissues down below. So, again, the partial pressure of oxygen in the tissues, we can see at its lowest end is right around 20 tors And notice that hemoglobin saturation in the tissues is only 32%, which means that if we subtract, if we do 98% minus 32%, we'll get 66%. And, 66% is how much oxygen is released. So, O₂ released by hemoglobin. And so, that is a good percentage of oxygen. And, if we do the same for myoglobin saturation in the tissues, notice that it's on it's, it's at 95%. And so if we do 99% minus 95%, that's only 4% oxygen release. And so 4% is really, really low. That's not enough oxygen to be delivered to the tissues and that's why again myoglobin is such a poor deliverer of oxygen to the tissues. And so the last point here that I want to leave you guys off with is that these, this hemoglobin curve, because it is an allosteric protein, it can actually be affected by other allosteric effectors, heterotropic allosteric effectors such as BPG for instance, which we'll talk more about later in our course. And BPG can further enhance hemoglobin's release of oxygen to the tissues making hemoglobin an even better oxygen transporter and deliverer to the tissues. And so here, what we've emphasized is that hemoglobin's positive cooperativity makes it a better transporter, oxygen transporter than myoglobin as we move forward in our course, we'll be able to apply a lot of these concepts that we've learned. So, I'll see you guys in our next video.

Oxygen is a _____________ allosteric _____________ that promotes additional O₂ binding to hemoglobin.

• A. Heterotropic, Repressor.
• B. Homotropic, Activator.
• C. Heterotropic, Activator.
• D. Homotropic, Repressor.

The binding of Oxygen to stabilize the R-state of Hemoglobin is best explained by which model(s)?

• A. Concerted Model.
• B. Sequential Model.
• C. Neither.
• D. Combination of Both.

Here’s what students ask on this topic:

What is positive cooperativity in hemoglobin?

Positive cooperativity in hemoglobin refers to the phenomenon where the binding of one oxygen molecule to a hemoglobin subunit increases the affinity of the remaining subunits for oxygen. This results in a sigmoidal (S-shaped) oxygen binding curve. Hemoglobin has four subunits, and when one subunit binds to oxygen, it induces a conformational change from the tense (T) state to the relaxed (R) state, making it easier for the other subunits to bind oxygen. This cooperative binding is crucial for efficient oxygen transport and release in the body, allowing hemoglobin to deliver oxygen more effectively to tissues compared to myoglobin, which does not exhibit cooperativity.

How does hemoglobin's oxygen binding curve differ from myoglobin's?

Hemoglobin's oxygen binding curve is sigmoidal (S-shaped) due to its positive cooperativity, meaning that the binding of one oxygen molecule increases the affinity for subsequent oxygen molecules. This allows hemoglobin to efficiently load oxygen in the lungs and release it in tissues. In contrast, myoglobin's oxygen binding curve is a rectangular hyperbola, indicating a high affinity for oxygen even at low partial pressures. Myoglobin binds oxygen tightly and does not release it easily, making it less effective as an oxygen transporter compared to hemoglobin. This difference is due to myoglobin having a single subunit, which does not exhibit cooperativity.

What are the concerted and sequential models of hemoglobin cooperativity?

The concerted and sequential models explain hemoglobin's positive cooperativity. The concerted model (MWC model) suggests that all subunits of hemoglobin transition between the tense (T) state and the relaxed (R) state simultaneously. In this model, the binding of oxygen to one subunit increases the probability that all subunits will switch to the R state. The sequential model (KNF model) proposes that subunits transition individually from the T state to the R state upon oxygen binding. Each binding event increases the affinity of neighboring subunits for oxygen. Hemoglobin's actual behavior is best explained by a combination of both models, displaying features of both concerted and sequential transitions.

Why is hemoglobin a better oxygen transporter than myoglobin?

Hemoglobin is a better oxygen transporter than myoglobin for two main reasons. First, hemoglobin exhibits positive cooperativity, allowing it to release oxygen more effectively in tissues. This means that as one oxygen molecule binds, the affinity for subsequent oxygen molecules increases, optimizing oxygen delivery. Second, hemoglobin displays the threshold effect, releasing more oxygen to tissues with lower oxygen levels, which are typically more active and in greater need of oxygen. Myoglobin, on the other hand, has a high affinity for oxygen and does not release it easily, making it less effective for oxygen transport despite its ability to bind oxygen tightly.

How does partial pressure of oxygen affect hemoglobin's oxygen affinity?

The partial pressure of oxygen (pO₂) significantly affects hemoglobin's oxygen affinity. At low pO₂, hemoglobin is primarily in the tense (T) state, with low affinity for oxygen. As pO₂ increases, oxygen binding induces a conformational change to the relaxed (R) state, increasing hemoglobin's affinity for oxygen. This results in a sigmoidal oxygen binding curve. In the lungs, where pO₂ is high, hemoglobin binds oxygen efficiently. In tissues, where pO₂ is lower, hemoglobin releases oxygen more readily. This dynamic response to pO₂ levels allows hemoglobin to effectively transport and deliver oxygen throughout the body.