BPG Regulation of Hemoglobin - Video Tutorials & Practice Problems
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BPG Regulation of Hemoglobin
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6m
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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 23 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. Now this molecule 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 hemoglobins 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 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 non covalent 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 and units of tors 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.
2
concept
BPG Regulation of Hemoglobin
Video duration:
4m
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Video transcript
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 going to be 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 quite a 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 c 02 and the high h plus that's present in the tissues. And the the c02 and h plus is 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, that 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 very high concentration of oxygen in the lungs, a high o two 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 it's 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.
3
concept
BPG Regulation of Hemoglobin
Video duration:
5m
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Video transcript
In this video we're going to talk about physiological regulation of BPG concentrations. And so what's important to note is that in our erythrocytes or red blood cells, the normal BPG concentrations at sea level are right around 5 millimolar. However, this BPG concentration of 5 millimolar at sea level can actually be modified to regulate hemoglobin's oxygen binding under different conditions. And so at very, 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. And so, if we take a look at our oxygen binding curve down below, notice on the y axis we have the fractional saturation theta or y and on the x axis what we have is the partial pressure of oxygen in units of tors. And so notice that we have these 3 vertical dotted lines going here, here, and right over here. And notice that this one over here on the far right represents the partial pressure of oxygen in the lungs, specifically at sea level, which is right around a 100 tors. Then 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. And here we're showing it at 50, tors which is half of the partial pressure at sea level here. And then, of course, on the far right, what we have is the partial pressure of oxygen in the tissue which is still right around 20 tors. And so that's exactly what we were mentioning up above that 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. And so, we as humans are able to physiologically regulate the concentration of BPG, in our red blood cells. And so 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. So from the normal 5 millimolar all the way up to 8 millimolar. And what this does is it allows our hemoglobin molecules to maintain maintain very similar oxygen release, as they had at sea level. And so if we take a look down below, at our oxygen saturation curve, notice that we have these 3 different curves. We have this black curve right here that represents hemoglobin's oxygen binding when there's 0 millimolar BPG. And then we have this blue curve here that represents hemoglobins oxygen binding, under normal conditions essentially color coded to this blue, at sea level for those of you that live at sea level. So this would be right around 5 millimolar BPG. And then, of course, what we have is 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 8000000 BPG. So, basically, what you can see is that the higher value of BPG, the higher concentration of BPG, will cause hemoglobin's binding curve to shift further to the right. And, of course, a shift further to the right, correlates with increased oxygen release. So releasing even more oxygen. And that's going to be helpful when at high altitudes, our ox our hemoglobin molecules are not binding very much oxygen. So again, in order to maintain similar oxygen release, they have to be able to release even more oxygen. And so, what's important to note here is that people that have anemia which is defined as low red blood cell count, they're also going to have low hemoglobin. And so they need to be able to account for the lowered hemoglobin that they have, by increasing their BPG as well. So they have higher BPG in their blood to help increase oxygen release, and accommodate for the fact that they have less hemoglobin molecules. And really, all of this effect here is part of the reason why athletes like to train at high altitudes because when f, athletes train at high altitudes, they can acclimate their cells to releasing higher BPG concentrations. And of course, that 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. And so, this year, concludes our lesson on physiological regulation of BPG concentration, and we'll be able to get some practice utilizing these concepts here in our next few videos. So I'll see you guys there.
4
Problem
Problem
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.
5
Problem
Problem
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.
6
Problem
Problem
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.