Hemoglobin Carbonation & Protonation - Online Tutor, Practice Problems & Exam Prep

Hemoglobin carbonation (HbCO₂) and protonation (HHb⁺) are crucial processes occurring primarily in tissues. HbCO₂ forms when hemoglobin binds carbon dioxide, stabilizing the tense state (T state) and promoting oxygen release. Conversely, protonation occurs as hemoglobin captures hydrogen ions in low pH conditions, also stabilizing the T state. In the lungs, low CO₂ and high pH facilitate oxygen binding and release of CO₂ and H⁺, transitioning hemoglobin to the relaxed state (R state). Understanding these mechanisms is vital for grasping oxygen transport dynamics.

Hemoglobin Carbonation & Protonation

In this video, we're going to begin our discussion on hemoglobin carbonation and protonation. So at this point in our course, we already know that hemoglobin can bind to carbon dioxide via carbonation and it can also bind to protons via protonation. Now in this video, we're mainly going to talk about hemoglobin carbonation, but in our next video, we'll talk about hemoglobin protonation. Now most of the information in this video is actually going to be review from our previous lesson videos, but we are going to reveal some critical information about hemoglobin carbonation that you guys should be familiar with. So we already know that hemoglobin carbonation can be referred to as just HbCO2, and hemoglobin carbonation occurs mainly in the tissues, not in the lungs. Now this allows hemoglobin to directly transport some small amount, about 10% of the carbon dioxide from the tissues to the lungs.

Now this next bullet point here is going to reveal the critical information that we need to know about hemoglobin carbonation. At this point, we know that hemoglobin has 4 separate subunits. Each of hemoglobin's 4 separate subunits can actually bind to a carbon dioxide molecule, forming a carbamate group on each of the free alpha amino groups on each of hemoglobin subunits to form what we call carbaminohemoglobin, which is just hemoglobin, with carbamate groups bound. And again, this is what we're going to refer to as HbCO2.

And so, if we take a look at our image down below, notice we're showing you the formation of carbaminohemoglobin. Notice that this molecule over here on the far left is our CO2 molecule, our carbon dioxide molecule. And then in red right here, what we have is hemoglobin's terminal amino acid residue. Essentially, the free alpha amino group is right here at this position. And so, notice that this reaction right here will release a proton, and in the meantime, it forms the carbaminohemoglobin. And so this is going to have just a carbon dioxide molecule attached as a carboxylate group, and together, this carboxylate group attached to this nitrogen here forms the carbamate group. And, together, this entire thing is referred to as carbaminohemoglobin, HbCO2.

And what's important to note is that, again, this is just showing the reaction for just one of the subunits of hemoglobin, interacting with CO2. However, remember that each of hemoglobin's subunits can undergo this reaction. And so what this means is that if we consider the hemoglobin's 4 subunits, each of the 4 subunits can bind a CO2 molecule. And so 4 CO2 molecules can be transported by 1 hemoglobin. And so, recall from our previous lesson videos that hemoglobin carbonation stabilizes the T state, which is the tense state, and binds ligand or oxygen inefficiently. And so if we stabilize the T state, that's going to cause the release of oxygen.

And so notice over here on the left where hemoglobin is carbonated, it's present in the T state. Notice it's not bound to any oxygen. And so, the reason for this is because in the tissues, there's such a high partial pressure of carbon dioxide, lots of carbon dioxide being produced in the tissues. And so there's so much carbon dioxide that hemoglobin is bound to bind to some of that carbon dioxide. So hemoglobin gets carbonated at these high partial pressures, and, of course, that stabilizes the T state and causes the release of oxygen. And so that's why we can see over here, we have the T state of hemoglobin in the tissue.

So here, we have a bicep to represent the tissues. And, again, this has to do with the high partial pressure of carbon dioxide in the tissues so high that hemoglobin is bound to bind to some of that CO2. Now in the lungs, there's the complete opposite condition of low partial pressure of CO2 in the lungs because, we're constantly exhaling CO2. And so because we're breathing out all of that CO2, hemoglobin is going to be decarbonated, essentially releasing the CO2 so that it can be exhaled as well. And now the hemoglobin molecule is going to be in the R state when it's in the lungs. And, again, this has to do with the low partial pressure of CO2 in the lungs.

And so, basically, the main takeaway here is that hemoglobin carbonation occurs only in the tissues as we can see over here. And, essentially, carbaminohemoglobin is just referring to hemoglobin that's bound to CO2 molecules. This here concludes our lesson on hemoglobin carbonation. We'll be able to get a little bit of practice in our next video, and then we'll move on to hemoglobin protonation. So I'll see you guys in our next video.

Which option best corresponds with the effect of CO₂ on hemoglobin's O₂-binding?

• A. Hb's O₂-affinity decreases with lower CO₂ concentration.
• B. Hb's O₂-affinity increases with higher CO₂ concentration.
• C. Low pCO₂ stabilizes the T state conformation of Hemoglobin.
• D. High pCO₂ stabilizes the R state conformation of Hemoglobin.
• E. High pCO₂ stabilizes the T state conformation of Hemoglobin.

Hemoglobin Carbonation & Protonation

So now that we've covered hemoglobin carbonation, in this video we're going to focus on hemoglobin protonation, which we already know from our previous lesson videos can be abbreviated as just HHB⁺. And just like hemoglobin carbonation, hemoglobin protonation occurs only in the tissues, not in the lungs. What's important to note about hemoglobin protonation is that hemoglobin can actually become protonated on several amino acid R groups in order to carry H⁺ as HHB⁺. Because it's these R groups that are susceptible to protonation, this means that there are more protonation sites than carbonation sites. Recall in our previous lesson video when we talked about hemoglobin carbonation, we said that it's only the free alpha amino groups that can be carbonated, and there are only 4 free alpha amino groups, so there are only 4 carbonation sites. However, here with hemoglobin protein, it's the R groups that are being protonated. And so there are several amino acid R groups that can be protonated in the hemoglobin structure. Notice down below, here we're showing the hemoglobin structure being protonated, and notice that there are way more protonation sites than carbonation sites. What's important to know is that in the relatively high concentration of hydrogen ions or low pH of the tissues, there is so much hydrogen ion concentration that hemoglobin is bound to grab onto one of those hydrogen ions and become protonated to form HHB⁺. This stabilizes the T state and releases oxygen. If we look below, you'll see that when hemoglobin is protonated as HHB⁺, it stabilizes the T state, releasing oxygen, and this is all due to the low pH in the tissues or the high hydrogen ion concentration in the muscle tissues. Now in the lungs, we have the complete opposite concentration of hydrogen ions. We have a very low concentration of hydrogen ions or a high pH in the lungs, and such a low concentration of hydrogen ions. And when it releases H⁺, it can then bind to all of the oxygen that's present in the lungs, allowing it to bind oxygen in the R state. Again, this is due to the high pH in the lungs and the low concentration of hydrogen ions. Hemoglobin protonation specifically occurs in the tissues. And again, that is really the main takeaway here: that both hemoglobin protonation and hemoglobin carbonation occur in the tissues and not in the lungs. I'll see you guys in our next video where we'll be able to apply some of these concepts.

Which statement is true about protons binding to hemoglobin?

• A. Protons stabilize the T-state increasing the affinity of hemoglobin for oxygen.
• B. Protons stabilize the T-state decreasing the affinity of hemoglobin for oxygen.
• C. Protons stabilize the R-state increasing the affinity of hemoglobin for oxygen.
• D. Protons stabilize the R-state decreasing the affinity of hemoglobin for oxygen.

Hemoglobin Carbonation & Protonation

In this video, we're going to do a quick recap on hemoglobin carbonation and protonation. Notice looking down below at our image on the left-hand side, we're zooming in specifically into the bloodstream by the tissues. Notice that in the tissues, we have a very high concentration of CO₂, which is going to lead to a high concentration of H⁺ in the tissues. There's so much CO₂ and so much H⁺ in the tissues that hemoglobin is bound to bind to the H+CO2. When it binds to the H+CO2, it's going to be in its T state and release oxygen. Myoglobin can facilitate the oxygen diffusion into the tissues.

Now in the lungs, on the other hand, notice that there's the exact opposite conditions as the tissues. There's a very low concentration of CO₂, and this low concentration of CO₂ translates to the inside of the red blood cell. The low CO₂ causes these equilibriums to shift to the right to compensate, decreasing the concentration of hydrogen ion. So we have a low concentration of CO₂ and a low concentration of hydrogen ion. It's so low that hemoglobin is bound to release some of its hydrogen ion so that it can also participate in this shift to the right, and it can release its CO₂ so that it can be breathed out of the cell. When it releases the H+CO2, it can also bind to the very high concentration of oxygen that's constantly being breathed in. Hemoglobin is going to bind the oxygen, release the H⁺ and CO₂, and be present in its R state when it's in the lungs.

This is our brief recap on hemoglobin carbonation and protonation. We'll be able to talk more about these ideas as we move forward in our course. So, I'll see you guys in our next video.

Alkalemia is a disease associated with an abnormal increase in the pH of a patient's blood due to rapid breathing (hyperventilation). How would alkalemia affect the oxygen binding affinity of the patient's hemoglobin?

• A. P₅₀ and oxygen affinity decrease.
• B. P₅₀ and oxygen affinity increase.
• C. P₅₀ decreases and oxygen affinity increases.
• D. P₅₀ increases and oxygen affinity decreases.
• E. P₅₀ and oxygen affinity remain the same.

Choose all of the following molecules that, when bound, trigger hemoglobin's transition from T to R state.

• A. CO₂
• B. CO
• C. O₂
• D. 2,3-Bisphosphoglycerate
• E. H⁺

Here’s what students ask on this topic:

What is hemoglobin carbonation and how does it occur?

Hemoglobin carbonation (HbCO₂) occurs when hemoglobin binds to carbon dioxide (CO₂) in the tissues. Each of hemoglobin's four subunits can bind to a CO₂ molecule, forming a carbamate group on the free alpha amino groups. This process stabilizes the tense state (T state) of hemoglobin, promoting the release of oxygen. The reaction can be represented as:

${\mathrm{Hb}}_4+4{\mathrm{CO}}_2\to {\mathrm{HbCO}}_2+4H_{+}$

This process occurs mainly in the tissues where the partial pressure of CO₂ is high.

How does hemoglobin protonation affect oxygen release?

Hemoglobin protonation (HHb⁺) occurs when hemoglobin binds to hydrogen ions (H⁺) in the tissues, where the pH is low. This protonation stabilizes the tense state (T state) of hemoglobin, which promotes the release of oxygen. The reaction can be represented as:

${\mathrm{Hb}}_4+4H_{+}\to {\mathrm{HHb}}_{+}$

This process ensures that hemoglobin releases oxygen in the tissues where it is needed most.

Why does hemoglobin release CO₂ and H⁺ in the lungs?

In the lungs, the partial pressure of CO₂ is low and the pH is high. These conditions favor the release of CO₂ and H⁺ from hemoglobin, transitioning it to the relaxed state (R state). This allows hemoglobin to bind oxygen efficiently. The reactions can be represented as:

${\mathrm{HbCO}}_2\to {\mathrm{Hb}}_4+4{\mathrm{CO}}_2$

${\mathrm{HHb}}_{+}\to {\mathrm{Hb}}_4+4H_{+}$

This ensures efficient oxygen uptake in the lungs.

What is the difference between hemoglobin carbonation and protonation?

Hemoglobin carbonation (HbCO₂) involves the binding of carbon dioxide (CO₂) to hemoglobin, forming carbamate groups on the free alpha amino groups. This process stabilizes the tense state (T state) and promotes oxygen release. In contrast, hemoglobin protonation (HHb⁺) involves the binding of hydrogen ions (H⁺) to various amino acid R groups in hemoglobin, also stabilizing the T state and promoting oxygen release. While carbonation occurs at four specific sites, protonation can occur at multiple sites due to the presence of several protonatable R groups.

How does the partial pressure of CO₂ affect hemoglobin's state?

The partial pressure of CO₂ significantly affects hemoglobin's state. In tissues, where the partial pressure of CO₂ is high, hemoglobin binds to CO₂ and stabilizes the tense state (T state), promoting oxygen release. Conversely, in the lungs, where the partial pressure of CO₂ is low, hemoglobin releases CO₂ and transitions to the relaxed state (R state), facilitating oxygen binding. This dynamic ensures efficient oxygen delivery to tissues and uptake in the lungs.