Question

Hemoglobin is the main protein in red blood cells and performs the function of transporting oxygen. Oxygen is combined into the hemoglobin's prostatic group, heme molecule.

A. Describe the changes in the quadratic structure of hemoglobin with oxygen binding and explain the role of the 2,3-BPG.

B. Describe the reasons for oxygen deficiency in the highlands and the body's action in adapting to high-altitude hypoxic environments.

C. Describe the bohr effect that affects the oxygenation of hemoglobin.

Answer 1

Structure of Heme:

It consists of an organic component and a central iron atom. The organic component (protoporphyrin) is made up of four pyrrole rings linked by methene bridges to form a tetrapyrrole ring.

Sixth coordination site remains unoccupied in Deoxyhemoglobin. oxygen-binding at the sixth coordination site of the iron rearranges the electrons within the iron such that it becomes effectively smaller, allowing it to move into the plane of the porphyrin.

The three-dimensional structure of hemoglobin has a pair of identical αβ dimers (α1β1 and α2β2) that associate together to form the hemoglobin tetramer.

αβ dimers are linked by an extensive interface in deoxyhemoglobin. This interface includes the carboxyl terminus of each chain. The heme groups are well separated in the tetramer with iron-iron distances (24 to 40 Å). The deoxy form corresponds to the T state in the context of either the concerted or the sequential model for hemoglobin cooperativity. Oxygen binding leads to substantial changes in quaternary structure that correspond to the T-to-R state transition.

The α1β1 and α2β2 dimers rotate 15 degrees with respect to one another. Thus, the interface between the α1β1 and α2β2 dimers is most effected by this structural transition.

Oxygen binding lead to the structural transition from the T state to the R state:

Iron ion moves into the plane of the porphyrin. Thereafter, the histidine residue bound in the fifth coordination site moves with it. Histidine residue is part of an α helix that also moves. The carboxyl terminal end of α helix lies in the interface between the two αβ dimers. Therefore, the structural transition at the iron ion transmitted to the other subunits. This dimer interface rearrangemnet gives a pathway for communication between subunits, enabling the cooperative binding of oxygen.

2,3-bisphosphoglycerate (2,3-BPG) is present in red blood cells at approximately the same concentration as that of hemoglobin. Its absence makes hemoglobin an extremely inefficient oxygen transporter. A molecule of 2,3-BPG binds in a pocket, which is present in the T form, in the center of the hemoglobin tetramer. When there is T-to-R transition, this pocket collapses. Thus, 2,3-BPG binds to deoxyhemoglobin and reducing the oxygen affinity. The bonds between hemoglobin and 2,3-BPG must be broken and 2,3-BPG must be expelled so that the structural transition from T to R to take place.

2.In highlands, there is less pressure, which results in oxygen molecules being further. Because,there is less pressure to "push" them together. Thus fewer oxygen molecules in the same volume of air as we inhale. This is called "hypoxia".

In high lands, body initially develop inefficient physiological responses. Later, acclimatization takes place. This broadly includes:

a. Additional red blood cells and capillaries are produced to carry more oxygen.

b. The lungs increase in size to facilitate the osmosis of oxygen and carbon dioxide.

c. An increase in the vascular network of muscles which enhances the transfer of gases.

3. Bohr effect was given by the Danish physiologist Christian Bohr in 1904. Hemoglobin's oxygen binding affinity is inversely related to acidity and to the concentration of carbon dioxide. The Bohr effect clearly refers to the shift in the oxygen dissociation curve that can be caused by changes in the concentration of carbon dioxide or the pH of the environment.