In the last article I mentioned that red blood cells contain a protein called haemoglobin. In simple terms, the haemoglobin protein binds to oxygen and carries it around the body. As with most of biology there’s a bit more to it than that, so here we will look at how this process works in more detail. It’s going to be a long one but it all links together.
The Haemoglobin Protein
Haemoglobin (Hb) is a conjugated protein with a quaternary structure. We already looked at the structure in the protein article but we’ll have a quick recap:
- Hb is made up of four polypeptide chains.
- Each polypeptide chain contains a prosthetic group called haem. This contains iron ions which are what actually binds to the oxygen.
In the lungs, Hb binds to oxygen and becomes oxyhaemoglobin (HbO8). At respiring cells, the oxygen dissociates from Hb. This is why the below reaction is reversible.
Haemoglobin Saturation and the Dissociation Curve
Before we get into the difficult bit, there are a couple of definitions you need to understand. Firstly, Hb has a high affinity for oxygen. That just means that it will readily combine with oxygen. However, the affinity for oxygen can vary depending on the partial pressure of oxygen (pO2). You can think of the partial pressure as a measure of concentration. So if an area has a high pO2, there is a high concentration of oxygen.
- If the pO2 is high, Hb will combine with oxygen to form HbO8. This happens in the capillaries surrounding the alveoli where oxygen is diffusing into the blood.
- If the pO2 is low, HbO8 will unload the oxygen. This happens in the capillaries near to respiring cells which are using oxygen up.
A dissociation curve helps us to see how saturated with oxygen Hb is at any pO2. Saturation is a measure of how much oxygen the Hb is carrying. A saturation of 100% means that all the available haemoglobin proteins have four molecules of oxygen bound to them – there is no room for any more oxygen at all. A saturation of 0% means no oxygen is bound to any haemoglobin at all.
You can see that the curve has a S-shape rather than being a straight line. That’s because sometimes it’s easier or harder for more oxygen to combine. When the first molecule of oxygen combines, the shape of the Hb protein changes shape slightly which makes it easier for the next molecule of oxygen to join in. So there’s a steep bit in the middle of the curve where oxygen combines more easily. But near the top of the curve when saturation is quite high, it is harder for more oxygen to combine.
The Bohr Effect and Fetal Haemoglobin
Now we know what the normal adult Hb dissociation curve looks like, but sometimes the curve can be shifted to the left of to the right. One thing that can shift the curve to the right is if there is a high partial pressure of carbon dioxide (pCO2). This might be the case in respiring tissues where CO2 is being produced. When the curve is shifted right due to high CO2 (called the Bohr effect), the affinity for oxygen is lower for any given pO2. This means that it is easier for oxygen to be unloaded just where it is needed – clever! We’ll come back to the mechanism behind this in the last section.
Next, fetal haemoglobin (found in a developing fetus) has a curve that is shifted to the left relative to adult haemoglobin. It has a higher affinity for oxygen at any given pO2, meaning it is easier for oxygen to combine. This is because a fetus is getting its oxygen from the mother’s blood – by the time it reaches the fetus, the mother’s body has already taken some of the oxygen, so the fetus has to be able to deal with those lower levels and still get enough for itself.
We have only really looked at human haemoglobin in this article, but be aware that other species can have slightly different haemoglobin proteins which are well adapted for their environment. For example, an organism living in an oxygen depleted environment might have a dissociation curve shifted well over to the left so that it can easily combine with what little oxygen it does have.
Carbon Dioxide and Oxygen Unloading
Ok last section, I promise. We mentioned the Bohr effect happening when pCO2 is high. Let’s have a look at the mechanism behind that, helped by diagrams.
- In respiring tissue, CO2 is being produced and the pCO2 is high. O2 is needed by the tissue cells and needs to be unloaded from Hb. The CO2 diffuses into the red blood cell. Most of it combines with water to form carbonic acid (H2CO3) – this is catalysed by an enzyme called carbonic anhydrase. A small amount of CO2 binds directly to Hb.
- Carbonic acid dissociates into H+ ions and HCO3– ions. The H+ ions bind to Hb in place of the O2, so O2 is unloaded and free to diffuse into the tissue. Goal achieved. And just as well this happens, otherwise the pH of the blood would become too acidic from the H+ ions. (Note: when Hb binds to H+ it is called haemoglobinic acid.)
- HCO3– ions diffuse into the plasma. But now the charge balance has been disrupted, so some negatively charged chloride ions diffuse into the red blood cells to keep it evened out. This is called chloride shift.
When the blood reaches the alveoli, the pCO2 is low and the opposite process happens. The H+ ions unload from Hb and recombine with HCO3– ions to form CO2 and water. O2 combines with the haemoglobin instead. CO2 diffuses out of the blood and into the alveoli to be breathed out. Chloride ions diffuse back out of the red blood cell to keep the charge balanced.
Summary
It’s all very clever isn’t it, but also a complex topic. We’ve now reached the end of the human circulatory and gas exchange system, so hopefully you can see how everything links together to make sure that respiration can continue in our cells. Here’s a few main points from today:
- Haemoglobin (Hb) combines with oxygen to form oxyhaemoglobin.
- The dissociation curve shows the saturation of Hb with oxygen at any given partial pressure of O2.
- The Bohr effect is where the dissociation curve is shifted to the right when the partial pressure of CO2 is high. This helps oxygen to be unloaded at respiring tissues. The mechanism involves the enzyme carbonic anhydrase and chloride shift.
- Fetal haemoglobin has a higher affinity for O2 so the dissociation curve is shifted to the left.
