Haemoglobin and oxygen transport

I remember when I first learned about haemoglobin. I was amazed by the way it works. It's affected by many different factors to "sense" the environment and respond to it. Very different from the perfluorocarbon which carries oxygen by solubilizing it. For perfluorocarbons, oxygen solubility is maybe slightly dependent on the temperature, pressure, etc but not much on pH and some important chemical ques. Haemoglobin, however is sensitive to all these factors and changes its oxygen carrying ability accordingly. In addition, the carrying level changes drastically when in different concentrations of oxygen. As I will elaborate on later, this is important in improving the efficiency of oxygen transport.


Before I get explain the amazingness of haemoglobin, I will talk briefly about what it is. As you may be aware, this is a protein that has heme (figure 1) as its prosthetic group (AKA non amino acid component. The heme group is an iron chelator and the iron is what binds to the oxygen in a manner shown in Figure 2.

Figure 1

Figure 2 Oxygen binding with heme group within the crevice in haemoglobin

In our body actually, there are at least two different proteins that can bind oxygen: myoglobin and haemoglobin. However, haemoglobin is used as oxygen carriers and is in circulation while myoglobin is mostly used as oxygen storage and located in muscle tissue [1]. Why is that? The following oxygen binding curve (Figure 3) may provide some insight as to why. On the x-axis of the curve is the pO2 which represents the partial pressure of oxygen. Intuitively, this is referring the the amount of oxygen in the blood with higher numbers reflecting higher oxygen content. The y-axis is the fractional saturation which refers to the fraction of protein that is oxygen bound.
This graph is interesting for biochemists because of the shape of the haemoglobin's oxygen binding behaviour - it's sigmoidal, which means the slope of the curve is low at first, getting higher, and then lower. Oxygen binding behavior of myoglobin on the other hand is more "normal". As more oxygen binds, the the slope of the curve is decreased. Intuitively, the "oxygen binding ability" is decreased. However, it is important to note that there two different myoglobins - oxygen-bound and free. There are no kind of oxygen-bound (technically, there are myoglobins in the "transition" state, but it is assumed to be neglectable).

Figure 3 oxygen binding curve for myoglobin and haemoglobin

This funny shape has been explained through the concept of cooperative binding... a topic for another post perhaps. Here, however, we can easily understand the consequence of lower slope. The binding level between tissues and lungs change drastically. To be an effective oxygen carrier, it should load oxygen (high binding to oxygen) in the lungs (~100 torr O2) and unload in the tissues (~25 torr O2).
Haemoglobin's binding level changes from ~0.95 -> 0.4, which in a very simple model implies that around 0.55 oxygen molecules are transported (in actuality, it may not be that simple because the flow is continuous etc... I will introduce a few other interesting complexities). This is incontrast to myoglobin which holds tightly to the oxygen molecule both in the lung environment and tissue environment... unable to unload anything.

That's not all. Haemoglobin's binding changes depends on pH level as shown in figure 4. This is important in the body since pH near cells that are consuming oxygen rapidly is lower. This is because respiration releases carbon dioxide and decreases pH (increases H+ content) via a process shown figure 5. Effectively, this helps hamoglobin "unload" the cargo even farther and more importantly, preferentially to locations where oxygen is in most need.

Figure 4. pH dependence of haemoglobin's oxygen binding 

Figure 5. carbon dioxide mediated pH decrease.

Also, the carbon dioxide can reversibly react with some side chain of haemoglobin to form carbamate group. This stabilized the oxygen-unbound (deoxyhaemoglobin) further aiding in the unloading process. Equally importantly, haemoglobin also helps transport carbon dioxide back to the lungs where it would be expelled.

Perfluorocarbon is interesting? Sure, but haemoglobin is amazing. There are a lot more interesting features that control oxygen binding and the more mathematical model inclined readers should look up cooperative binding models. Maybe I will post something in the future.

refs:
[1] http://jeb.biologists.org/content/207/20/3441.full
[2] General biochemistry text (ex. Biochemistry by Voet and Voet; Biochemistry by Stryer, Tymoczko, and Berg)