Re: How does temperature influence Hb affinity for binding oxygen?

Hi Christian,

We can address this question from many levels, but I think I will focus mainly on how an enzyme, both in structure and activity, is affected by temperature. Hopefully this will be sufficient in answering your question.

For starters, we need to understand the effect temperature has on the energy of any given atom or molecule. We'll start small and work our way up. Take water for instance. The water molecule does not change over temperature, but the phase the molecule is in changes dramatically. At freezing temperatures, water is a solid. At most other temperatures it is a liquid and when it gets hot enough (above 100C), it becomes a gas.

Temperature has the ability to increase the energy of any given molecule or atom. This energy can be seen by how rapidly these molecules move. The faster they move, the less effective they are in interacting. For example, if you and a friend are talking, your conversation is much more effective while standing still than while running in opposite directions!

In the case of water, the lower the temperature, the slower the molecules move and the more interactions can/may take place. I state "can/may" only because not all atoms interact in the same way. Some may have negative effects, while others are positive. The higher the temperature, the more energy for the molecules to release from each other, hence liquid water becomes steam.

I know this is simple, but the same effect occurs for hemoglobin, just on a much larger scale.

Now, let's address how temperature effects enzyme activity. A protein can be thought of as a mixture of thousands upon thousands of atoms, some interacting, other repelling, and still others not even close enough to care. Any increase or decrease in temperature is going to ultimately effect how these atoms interact. In the case of proteins, the atomic interactions are what set up the secondary, tertiary and quaternary protein structures. These structures are defined by the atoms and are essential for activity.

Enzymes, all proteins for that matter, are highly dynamic. They are not static. They all have the ability to change shape and size within a given area and constraint. Much of this depends on what other molecules it interacts with.

In the case of hemoglobin, which is made up of four hemoglobin proteins (an example of a quaternery structure), binding to oxygen (O2) increases the affinity for the second hemoglobin to bind another oxygen. This is called cooperative binding. Once one O2 is bound, the other three hemoglobin proteins slightly change their structure and positioning, which favors O2 uptake of the next hemoglobin. This changes the molecule's structure and position again, which increases the affinity of O2 to hemoglobin even higher than before.

The interactions of these atoms are therefore essential for the proper folding, structure and activity of any enzyme. Just like with water, if you increase temperature you effect these interactions. At extremely low temperature, the proteins will be "frozen" in one form or another and not have the flexibility to interact with O2. At extrememly high temperatures, the proteins will not be able to interact with itself or other molecules and will essentially fall apart. (Think of the Ice-water-gas) All proteins need this type of fluid movement to work properly.

It is known that some animals live under conditions of different temperatures but it has been shown that their ability to bind O2 is most efficient at the temperature of their environmental condition coupled with their uptake and use of oxygen. Although this is true for all enzymes, differences in structure and sequence of the proteins themselves can influence how our hemoglobin works differently than a deep sea creature.

If you want to get even more detailed we can look at it from an atomic structure point of view.

Without going into much detail I will say that temperature greatly effects the binding of the Iron atom, within hemoglobin, and the O2 molecule. The Iron-Oxygen complex is essential for uptake of O2 by hemoglobin. The atomic forces working in these interactions require certain conditions that are greatly affected with an increase in temperature. The higher the temperature, the less stable the Iron-O2 complex, therefore hemoglobin binds less O2.

If you ever study thermodynamics and enyzme kinetics you will learn about free energy and enthalpy, and how these effect enzyme activity, as well as how they can be influenced by pressure and temperature. These are major players in fundamentally understanding the foundations of biochemistry.

I hope this helps!!

Matt