BPG Regulation of Hemoglobin - Online Tutor, Practice Problems & Exam Prep

BPG, or 2,3-bisphosphoglycerate, is a crucial allosteric inhibitor that reduces hemoglobin's oxygen affinity, particularly in tissues where it stabilizes the tense (T) state of hemoglobin. This interaction enhances oxygen release in low-oxygen environments, such as tissues with high CO₂ and H⁺ concentrations. In contrast, in the lungs, hemoglobin predominantly exists in the relaxed (R) state, where BPG binding is minimal. Physiological adaptations, such as increased BPG levels at high altitudes, facilitate oxygen release, demonstrating the importance of BPG in oxygen transport and regulation.

BPG Regulation of Hemoglobin

In this video, we're going to begin our discussion on BPG regulation of hemoglobin. So BPG is a molecule that actually does affect hemoglobin's oxygen binding activity. And so BPG is really just an abbreviation for the molecule 2,3-bisphosphoglycerate. And the "bi" here is a prefix that means 2, and the "phospho" is referring to phosphate groups. So BPG has 2 phosphate groups, just like what we can see down below in this image. We have a phosphate group over here and another phosphate group over here. And so this is referring to BPG's structure, which I don't expect you guys to be able to memorize. However, I want you to know that the naming has to do with the structure of the molecule.

Now, what I also want you guys to realize is that sometimes this prefix "bi" is replaced with "di", which also means 2. And so sometimes BPG is abbreviated as DPG instead. However, both DPG and BPG are referring to the same exact molecule down below. The only difference is just a little difference here, in this prefix "di" versus "bi". Now, moving forward in our course, I'm mainly going to be referring to this molecule as BPG because I found that it's more commonly referred to as BPG.

BPG, as we'll see moving forward, is really going to act as an allosteric inhibitor reducing hemoglobin's oxygen affinity in the tissues and allowing hemoglobin to release even more oxygen to the tissues when appropriate. And so what this means is that this molecule BPG is really going to have a very similar effect to carbon dioxide and protons on hemoglobin's oxygen binding activity. And so BPG is going to act just like a negative heterotrophic allosteric inhibitor of hemoglobin oxygen binding. And again, "hetero" is just referring to the fact that BPG is a different molecule than oxygen. The negative is referring to the fact that this is acting as an inhibitor to decrease hemoglobin's oxygen binding. And of course, recall from our previous lesson videos that negative heterotrophic allosteric inhibitors are going to cause the shift, the curve to shift towards the right. Just like carbon dioxide and protons did, for hemoglobin's activity. So again, you can really think of the effect of BPG as being very similar to the effect of carbon dioxide and protons.

Now, this molecule, BPG, is actually present within all of our erythrocytes, which again are our red blood cells. However, as we'll see moving forward, BPG is only going to affect hemoglobin when it's in the tissues. And part of the reason for that is because the binding site to hemoglobin, BPG's binding site to hemoglobin, it is only available when hemoglobin is in the t state. And so recall that the t state is the tense state that binds oxygen inefficiently. And so again, BPG, just like carbon dioxide and protons, is going to be stabilizing the t state further, because it binds to the t state. Now, because that's true, BPG is actually going to be always binding to deoxygenated hemoglobin. And of course, BPG is not going to be binding to hemoglobin covalently because that would indicate some kind of permanent or long-term interaction. Instead, BPG interacts with deoxygenated hemoglobin via electrostatic noncovalent interactions. Again stabilizing hemoglobin's t state as we already mentioned.

And so if we take a look at our image down below over here on the left-hand side, what you'll notice is we have a little equation to help you guys understand BPG's effect. And so, notice over here what we have is oxygenated hemoglobin. And in the presence of BPG, BPG can actually cause hemoglobin to release its oxygen. And so, really, this is the expression that we can think about, that shows how BPG can lead to more oxygen being released. Because, again, when BPG is present, it will bind to hemoglobin and cause it to release its oxygen.

Now over here, what we have is an oxygen saturation curve where we have \( \theta \) or \( y \), or the fractional saturation on the y-axis, and then we have the partial pressure of oxygen in units of torrs on the x-axis and we've got these 3 different curves here. We've got this black curve right here that represents hemoglobin's curve when there is absolutely no BPG that's present. And notice that it does have a slight sigmoidal curve, but it's not nearly as sigmoidal as these other two curves that we see over here. So, this next curve that we see here is basically hemoglobin with some BPG, not a lot, but some BPG. And notice that the curve is being shifted to the right, when we add BPG. With respect to the black curve right here. This curve that has some BPG is being shifted to the right. And then this last curve that we see here, this orangest one is hemoglobin with even more BPG. So, what you'll notice is that when we add even more BPG, hemoglobin's curve begins to take even more of a sigmoidal shape. And, really, we can see that BPG is acting as a negative heterotrophic allosteric effector because of this shift to the right that we see with these curves.

And so in our next video, we'll be able to talk more about how BPG only affects hemoglobin's oxygen activity when it's in the tissues and not in the lungs. So I'll see you guys in that video.

BPG Regulation of Hemoglobin

In this video, we're going to focus on the fact that BPG only affects hemoglobin's oxygen binding activity in the tissues and not in the lungs. And of course from our last lesson video, we know that BPG is a negative heterotrophic allosteric inhibitor, which means it's going to decrease hemoglobin's oxygen activity. And so BPG is only going to decrease hemoglobin's binding activity in the tissues. And the reason for this is because the conditions in the tissues lead to hemoglobin mainly being in the T state. And of course, as we know from our previous lesson video, it's the T state that accommodates a binding site for BPG. Now, on the other hand, BPG has a very minimal effect on the oxygen binding in the lungs since hemoglobin is mainly in the R state when it's in the lungs. And, of course, the R state does not accommodate a binding site for BPG. And so what's really important to note here is that one BPG molecule will actually bind per hemoglobin tetramer, not per hemoglobin subunit. And so what this means is that one BPG molecule is going to bind to the entire hemoglobin protein and there's not this 1 BPG binding per subunit. And so of course, as we already know, BPG binding is going to stabilize the T state, in the tissues. And, of course, that's going to cause hemoglobin to release oxygen. So if we take a look at our image over here on the left-hand side, what we can say is that there's a quite low concentration of oxygen in the tissues. And so upon arrival to the tissues, we know that hemoglobin is going to arrive from the lungs fully oxygenated. And so, as soon as this oxygenated hemoglobin arrives to the tissues it's going to encounter the high CO2 and the high H-plus that's present in the tissues. And the CO2 and H-plus are so high that it's going to bind to the hemoglobin and transition it into the T state causing hemoglobin to release its oxygen. And, of course, notice that when hemoglobin is in the T state, its BPG binding site is available. And so BPG is able to bind to the T state and further stabilize the T state over here. And so essentially, we have this equilibrium here by Le Chatelier's principle. If this is being shifted to the right through BPG binding, then this is going to decrease. And, if this decreases, then this equilibrium, in order to compensate by Le Chatelier's Principle, is going to shift even further to the right. So essentially, BPG binding leads to this equilibrium shifting even more to the right, which leads to even more oxygen release. So we associate BPG in the tissues with even more oxygen release. Now, on the other hand, over here on the right-hand side, what we have are the conditions in the lungs. And so, due to a very high concentration of oxygen in the lungs, high O₂ in the lungs due to constant inhalation of oxygen. Hemoglobin is mainly going to be in the R state when it's in the lungs. And, of course, the R state does not accommodate a site for BPG to bind. So, the R state lacks BPG's binding site. And so notice over here what we have is hemoglobin that is in the R state, again, due to the high concentration of oxygen. And when hemoglobin is in the R state, notice that BPG's binding site is not available. So, it simply cannot bind. And if it can't bind, then hemoglobin is gonna remain exactly the same and in its R state. And when it's in its R state, in the presence of such high oxygen in the lungs, it's capable of binding all of that oxygen. And so BPG, again, has a very minimal effect on oxygen binding in the lungs because it's always in the R state, mainly in the R state. And so, this here concludes our introduction to the effect that BPG has. And in our next video, we'll be able to talk more about the physiological regulation of BPG concentration. So I'll see you guys in that video.

BPG Regulation of Hemoglobin

In this video, we're going to talk about physiological regulation of BPG concentrations. It's important to note that in our erythrocytes, or red blood cells, the normal BPG concentrations at sea level are right around 5 millimolar. This BPG concentration of 5 millimolar at sea level can actually be modified to regulate hemoglobin's oxygen binding under different conditions. At very high altitudes, such as on top of Mount Everest, there is significantly less oxygen available in the atmosphere for hemoglobin to bind in comparison to sea level.

If we take a look at our oxygen binding curve below, notice on the y-axis we have the fractional saturation theta or y, and on the x-axis, we have the partial pressure of oxygen in units of torrs. Notice that we have these three vertical dotted lines going here, here, and right over here. The one on the far right represents the partial pressure of oxygen in the lungs, specifically at sea level, which is right around 100 torrs. You can see that the partial pressure of oxygen in the lungs, except at high altitudes like on top of a mountain for instance, can be significantly less depending on the height. Here we're showing it at 50 torrs, which is half of the partial pressure at sea level. On the far right, we have the partial pressure of oxygen in the tissue, which is still right around 20 torrs. This is what we were mentioning above: at high altitudes, there's less oxygen available in the atmosphere for hemoglobin to bind, and that's exactly what we're showing right here. Less oxygen, less partial pressure of oxygen.

We as humans are able to physiologically regulate the concentration of BPG in our red blood cells. In order to account for this low partial pressure of oxygen at high altitudes, blood BPG concentrations can be increased to a value of 8 millimolar. This increase from the normal 5 millimolar all the way up to 8 millimolar allows our hemoglobin molecules to maintain very similar oxygen release as they had at sea level.

If we take a look down below at our oxygen saturation curve, notice that we have these three different curves. We have this black curve right here that represents hemoglobin's oxygen binding when there's 0 millimolar BPG. We have this blue curve here that represents hemoglobin's oxygen binding under normal conditions, essentially color-coded to this blue, at sea level for those of you who live at sea level. This would be right around 5 millimolar BPG. Finally, we have this red curve right here, which is shifted to the right, and this corresponds with the hemoglobin oxygen binding curve at high altitudes, which is going to be increasing its BPG up to a value of 8 millimolar. As BPG concentration increases, hemoglobin's binding curve shifts further to the right, correlating with increased oxygen release.

This is going to be helpful when at high altitudes, our hemoglobin molecules are not binding very much oxygen. In order to maintain similar oxygen release, they have to be able to release even more oxygen. It's important to note here that people with anemia, which is defined as a low red blood cell count, are also going to have low hemoglobin. Thus, they need to increase their BPG to help increase oxygen release and accommodate for the fact that they have fewer hemoglobin molecules. This effect is part of the reason why athletes like to train at high altitudes: training there, they can acclimate their cells to releasing higher BPG concentrations. This adaptation allows their cells to acclimate to releasing even more oxygen when they return to sea level for that race or whatever it is that they are performing in athletically.

This concludes our lesson on physiological regulation of BPG concentration, and we'll be able to get some practice utilizing these concepts in our next few videos. See you guys there.

In hemoglobin, the equilibrium transition from R state to T state is triggered by:

• A. Fe²⁺ binding.
• B. Heme binding.
• C. Oxygen binding.
• D. 2,3-BPG binding.

A 9-month old girl with hemolytic anemia is found to have a deficiency in the enzyme responsible for the conversion of molecule-B to pyruvate. Shown below is the oxygen saturation curve for hemoglobin in the erythrocytes of this patient (green curve), compared to the corresponding black curve in normal red blood cells. Which of the following is the most likely explanation for the observed oxygen saturation curve in this patient?

• A. Decreased [BPG].
• B. Increased [BPG].
• C. Decreased blood glucose.
• D. Increased blood glucose.

What is the effect of the following changes on the O ₂ affinity of hemoglobin?

A) A drop in the pH of blood plasma from 7.4 to 7.2.

a) Lower the O₂ Affinity.     b) Increase the O₂ Affinity.

B) A decrease in the partial pressure of CO₂ in the lungs from 6 kPa (holding one's breath) to 2 kPa (normal).

a) Lower the O₂ Affinity.      b) Increase the O₂ Affinity.

C) An increase in [BPG] from 5 mM (normal altitudes) to 8 mM (high altitudes).

a) Lower the O₂ Affinity.     b) Increase the O₂ Affinity.

So here we have a 3-part practice problem broken up into part a, part b, and part c, and it's asking what is the effect of the following changes on the oxygen affinity of Hemoglobin? And so, Part A says, a drop in the pH of blood plasma from a value of 7.4 down to a value of 7.2. And of course, we know that a pH value of 7.2 is actually relatively acidic in comparison to a pH value of 7.4. And we also know from our previous lesson videos that a pH value of 7.2 actually corresponds with the pH of blood near the tissues. And so essentially, what we're saying here is that this scenario in part A corresponds with Hemoglobin's activity that we see in the tissues. And we know from our previous lesson videos that in the tissues, Hemoglobin is going to release all of its oxygen so that all of these hard-working muscle tissues can receive all of that released oxygen. And so what we're saying here is that this scenario corresponds with Hemoglobin releasing oxygen, and of course, released oxygen corresponds with a lowered affinity for oxygen. And so, because oxygen is being released in this scenario, we know that Hemoglobin is going to have a lower affinity for that oxygen. And so we can go ahead and cross off part B and indicate that the answer for part A is actually A. So now moving on to part B, it says, a decrease in the partial pressure of CO2 in the lungs from 6 kilopascals, which would be holding one's breath, down to 2 kilopascals, which would be normal breathing. And so maybe part B threw you guys off because it gives us these very specific values of the partial pressure of CO2. However, the exact values do not really matter so much for this part. Instead, what matters is that there's actually a decrease in the partial pressure of CO2. So, 6 kilopascals are greater than 2 kilopascals, And so what this means is that the partial pressure is decreasing. And so if we have a decreased partial pressure of CO2, that means we're going to have less CO2. And so what we need to recall from our previous lesson videos is that CO2 acts as a heterotropic allosteric inhibitor to Hemoglobin's oxygen binding affinity. And so if CO2 is acting as an inhibitor, and we have less of an inhibitor under these conditions, if we have less of an inhibitor, then we expect Hemoglobin's activity to increase. And so that would correspond with increased oxygen affinity. And so, we can say that the answer for part B is actually going to be B. And so we can cross off option a. So now moving on to our last part of our question here, it says, an increase in the BPG concentration from 5 millimolar, at normal altitudes, up to a value of 8 millimolar at high altitudes. And so what we need to recall from our previous lesson videos is that BPG, similar to CO2, is also a heterotropic allosteric inhibitor. And so if we are increasing the amount of inhibitor going from 5 up to 8, that's increasing the amount of inhibitor. Of course, that means that, more of Hemoglobin is going to be inhibited if we increase the amount of inhibitor. And that means that Hemoglobin is going to have a lower affinity for oxygen. And so we can go ahead and indicate that the answer for part C is A, and then we can cross off B. And so that concludes our 3-part practice problem and I'll see you guys in our next video.

Here’s what students ask on this topic:

What is BPG and how does it affect hemoglobin's oxygen binding activity?

BPG, or 2,3-bisphosphoglycerate, is an allosteric inhibitor that reduces hemoglobin's oxygen affinity. It binds to the T (tense) state of hemoglobin, which is the form that binds oxygen inefficiently. By stabilizing the T state, BPG promotes the release of oxygen in tissues where it is needed most, such as areas with high CO₂ and H⁺ concentrations. This interaction shifts the oxygen dissociation curve to the right, indicating a lower affinity for oxygen. In the lungs, where hemoglobin is in the R (relaxed) state, BPG has minimal effect because the R state does not accommodate BPG binding.

Why does BPG only affect hemoglobin in the tissues and not in the lungs?

BPG only affects hemoglobin in the tissues because hemoglobin is predominantly in the T (tense) state in these areas. The T state has a binding site for BPG, allowing it to stabilize this form and promote oxygen release. In contrast, in the lungs, hemoglobin is mainly in the R (relaxed) state due to the high concentration of oxygen. The R state does not have a binding site for BPG, so BPG cannot bind and thus has minimal effect on hemoglobin's oxygen binding activity in the lungs.

How does BPG concentration change at high altitudes and why?

At high altitudes, the concentration of BPG in erythrocytes increases from the normal 5 mM at sea level to about 8 mM. This increase is a physiological adaptation to the lower oxygen availability in the atmosphere at high altitudes. Higher BPG levels shift the oxygen dissociation curve to the right, promoting greater oxygen release from hemoglobin to the tissues. This adaptation helps maintain adequate oxygen delivery despite the reduced partial pressure of oxygen in the environment.

What is the role of BPG in individuals with anemia?

Individuals with anemia have a lower red blood cell count and consequently less hemoglobin. To compensate for this, their bodies increase the concentration of BPG in their erythrocytes. Higher BPG levels shift the oxygen dissociation curve to the right, enhancing oxygen release to the tissues. This adaptation helps to ensure that sufficient oxygen is delivered to the tissues despite the reduced hemoglobin levels.

Why do athletes train at high altitudes in relation to BPG?

Athletes train at high altitudes to acclimate their bodies to higher BPG concentrations. At high altitudes, the body increases BPG levels to compensate for the lower oxygen availability. This adaptation enhances oxygen release from hemoglobin to the tissues. When athletes return to sea level, their bodies retain the higher BPG levels for a period, allowing for more efficient oxygen delivery and improved performance during competitions.