Question

1. a. why does myoglobin with its single prosthetic group, exhibit hyperbolic O2 binding curve?

b. Describe O2 binding behavios of myoglobin in terms of pO2 and what does the term pO2 mean (significance)?

c. Explain the structural basis for cooperative oxygen binding to hemoglobin.

Answer 1

A why does myoglobin with its single prosthetic group, exhibit hyperbolic O2 binding curve:

Since myoglobin and hemoglobin both bind with oxygen so we can assume that there should be some similarities between their structures and there should also be some dissimilarities because of their different roles as oxygen binding proteins. One important difference between the two proteins is that myoglobin is a single polypeptide chain while hemoglobin is tetrameric i.e. Myoglobin (Mb) is a monomer having only one molecule of heme. The peptide chains in Hb and Mb have extensive helical structure. There are 7 helical segments in the α chains and 8 in the β and myoglobin forms. These are linked by short non-helical segments. Curves for oxygenation of Mb is hyperbolic while that of Hb is sigmoidal in nature. It is the cooperativity of the four-heme groups that produces two types of the curves. So cooperativity is responsible for this behavior.

B Describe O2 binding behavios of myoglobin in terms of pO2 and what does the term pO2 mean (significance)

Each Mb molecule have one heme prosthetic group inserted into a hydrophobic cleft in the protein. Each heme residue contains one central coordinately bound iron atom that is normally in the Fe²⁺ state. The oxygen carried by hemeproteins is bound directly to the ferrous of the heme prosthetic group. Hydrophobic interactions between the tetrapyrrole ring and hydrophobic amino acid R groups on the interior of the cleft in the protein strongly stabilize the heme protein conjugate. Also a nitrogen atom from a histidine R group located above the plane of the heme ring is coordinated with the iron atom further stabilizing the interaction between the heme and the protein. In oxymyoglobin the remaining bonding site on the iron atom (6th coordinate position) is occupied by the oxygen whose binding is stabilized by a second histidine residue. Carbon monoxide also binds coordinately to heme iron atoms in a manner similar to that of oxygen but the binding of carbon monoxide to heme is much stronger than that of oxygen.

In terms of pO2 Mb behaves more simply because it consists of only one unit of heme. Mb interacts with oxygen strongly even at lower oxygen pressure that is in muscles. While in higher pressure of oxygen Mb can interact with oxygen like Hb that is why it has hyperbola curve. The term pO2 mean partial pressure of the oxygen in the lungs and the muscles.

C Explain the structural basis for cooperative oxygen binding to hemoglobin.

Curves for oxygenation of Mb is hyperbolic while that of Hb is sigmoidal in nature. It is the cooperativity of the four-heme groups that produces two types of the curves. Deoxy hemoglobin is relatively uninterested in oxygen, but when one oxygen attaches, the second binds more easily, and the third and fourth easier yet. The same process works in reverse , once fully loaded hemoglobin lets go of one oxygen, it lets go of the next more easily, and so forth. This relationship is called cooperativity indicating that one hemoglobin subunit transmits information to the others. Hb is about as good an oxygen binder as Mb at high oxygen pressure. It is much poor at the lower pressures of O2 prevailing in muscle and hence passes its oxygen on to Mb as required.The need for oxygen will be greatest in tissues where O2 is consumed followed by production of CO2. The CO2 lowers the pH, thus causing the Hb to release even more oxygen to Mb. The pH-sensitivity (Bohr effect) as well as the progressive increase of O2 binding constants in Hb are due to the interaction between the subunits. Hence each of the two is essential in the complete oxygen transport process.