Hemoglobin/Oxygen Binding

The primary function of hemoglobin (Hb) is to transport oxygen. Since oxygen is not very soluble in water (the major constituent of blood), an oxygen transport protein must be used to allow oxygen to be 'soluble'. Hemoglobin (Hb) is the oxygen transport protein used in the blood of vertebrates. Below is a wireframe diagram of a hemoglobin molecule. It is composed of 4 polypeptide chains (represented in this diagram by different colors. Each chain contains one heme group (colored orange), each of which contains one iron ion (not shown). The iron is the site of oxygen binding; each iron can bind one O2 molecule thus each hemoglobin molecule is capable of binding a total to four (4) O2 molecules.

In humans, the average hemoglobin concentration is 16 g/100 ml. This means that there are approximately 150,500,000,000,000,000,000 hemoglobin molecules in 100 ml of whole blood. How many possible binding sites for oxygen are contained in 100 ml of blood? How many O2 molecules can be carried by 100 ml of blood if the hemoglobin is completely saturated (meaning every possible binding site is filled) with oxygen?

It is important that you remember that the purpose of Hb is to pickup oxygen at the lungs and to deliver it to the tissues. So Hb must be able to both bind and release oxygen and must be able to do these at the right places! You may want to think of this in regard to something that you understand such as the delivery of M&M's to Target stores. The M&M factory (here the lungs) produces M&M's (oxygen). In order to make money, the M&M's must be sold and one of the places that sells them are Target stores. Thus there must be a way to transport the M&M's to stores, including Target (the tissues). So, the M&M company has trucks (Hb) to deliver the M&M's. The trucks are completley filled at the M&M factory and then travel the highways and biways to the stores. When they arrive at the Target store, the truck unloads the M&M's and then returns back to the factory. Now, how many M&M's are delivered? It really depends on how many M&M's the store has sold since the last delivery. If, for example, no M&M's were sold, none would be delivered; if 10 boxes were sold, ten would be delivered. So, the amount of M&M's delivered depends on the amount of M&M's sold (used) by the store. This is the same with oxygen delivery to the tissues, Hb must be able to deliver more oxygen to those tissues that need more oxygen - tissues that use more oxygen need to have more oxygen delivered. Hb does this!

Oxygen Binding to Hemoglobin

The primary factor that determines how much oxygen is actually bound to hemoglobin is the partial pressure of oxygen (pO2) in the hemoglobin solution. For our purposes, only oxygen bound to Hb can be carried by blood. There is small amount that is dissolved in the plasma of the blood, however, this amount is physiologically insignificant and we will ignore it. This means that the maximum amount of oxygen that can be carried by blood is determined by the amount of Hb. When every oxygen binding site on all the Hb molecules are occupied by oxygen, the blood is said to be 100% saturated and the blood cannot carry any more oxygen. When half of the sites are filled with oxygen, the blood is said to be 50% saturated (I expect that you have the picture). The following graph demonstrates the effect that pO2 has on the percent saturation of Hb. This curve was created by a scientist who exposed Hb to different pO2 then determining the % saturation of Hb at each pO2.

How to read this graph:

To determine the % saturation of Hb at a given pO2, find the pO2 on X-axis and draw an imaginary line up until you reach the red curve. Then read the % saturation on the Y-axis. This has been done for you at two important points, a pO2 of 40 mm Hg (the pO2 that is normally at the capillaries in resting tissues) and a pO2 of 100 mm Hg (the pO2 that is normally in the capillaries in the lungs - this is constant and does not change under normal circumstances). Under normal circumstances, these are the only values that we must consider in a normal resting individual.

Find the arrow that originates from 100 mm Hg - you should be able to discover that the Hb will be about 97% saturated (which means that 97% of all oxygen binding sites will be occupied with oxygen) - just about 100 %. Since the pO2 of the capillaries in the lungs is 100 mm Hg (actually, it is a bit higher) , then the Hb in these capillaries will be almost completely saturated with oxygen. Since the pO2 of blood cannot change until the blood reaches the capillaries in the tissues, all arterial blood will be just about100% saturated and cannot not carry any more oxygen.

Now, find the arrow that originates from 40 mm Hg. At this partial pressure, the Hb is less saturated - about 70%. This is the typical pO2 in the capillaries of resting tissues. This means that the Hb in these capillaries are only 70% saturated. Since the blood entering these capillaries was 100% saturated (this blood is coming from the lungs) but is only 70% saturated when leaving the tissues. What happened to the other 30%? This oxygen was released from the Hb and is delivered to the tissues.

Now, imagine that the tissue is more active so that it is using more oxygen. This will mean that there is less oxygen (a lower partial pressure) in this tissue. Let us imagine that due to the increase use of oxygen by the tissue, the pO2 of the tissues is 30 mm Hg instead of the normal 40 mm Hg. If you check the graph, you will find that the % Hb saturation at this pO2 is about 61%. Since the blood entering these capillaries was 100% saturated (it is coming from the lungs) and is 61% saturated when leaving the tissues, the rest (39%) was released and delivered to the tissues. This is more oxygen then was delivered during normal conditions in which the pO2 is 40 mm Hg (remember the blood leaving the tissues in this case was about 70%, see above) which is what one would want to occur. If the tissue was so actve that the pO2 is ony 20 mm Hg, even more oxygen will be released - convince yourself that this is true by using the graph.

The bottom line is that Hb is made so that it will automatically deliver more oxygen to those tissues that are using more oxygen.

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