Oxygen Binding Protein: Hemoglobin and MyoglobinEdit
The major oxygen binding proteins are Hemoglobin and Myoglobin. They are slightly related in primary sequence. They have both groups have "heme" group. Myoglobin is protein located in the muscle used for oxygen storage. It provides supply of oxygen when oxygen is needed. Hemoglobin refers to proteins which found in red blood cells, oxygen binding protein, carry oxygen from the lung the deposit it through the cells of the body. Oxygen is critical to the body because it is needed for oxidative phosphorylation.
Characteristics of Oxygen Binding ProteinEdit
One critical feature of oxygen binding protein is the existence of a heme group at its binding site. A heme is a red prosthetic group which consists of iron and organic component where oxygen can bind to.
There are two binding sites on the heme group. Each lies on different plane of the heme. They are called the 5th and 6th coordination site. For both myoglobin and hemoglobin the 5th coordination site is occupied with an imidazole ring leaving the 6th coordination site available for oxygen binding. There are two configuration of the heme: one that lacks the oxygen and the one with the oxygen. With the configuration lacking oxygen, the iron lays a bit outside in reference to the porphyrin plane because it cannot fit in the center of the heme. In the configuration that binds to the oxygen, the iron lies on the same plane as the poryphin’s . The difference in position of the iron group is due to difference in the magnetic properties of each configuration. The form which lack oxygen, the iron’s electron cloud is too big which repels itself from the pyrophin plane. For the form with the oxygen, the oxgen which is very electronegative binds to iron and suck the electron cloud from the iron. The depletion of the iron’s electron cloud makes the iron smaller which enable it to fit into the center of the pyrophin plane. A diagram is shown below to illustrate what is written above.
Myoglobin is monomeric protein consisting of a single polypeptide chain. Each Myoglobin contains one binding site where it can bind to one oxygen. There are two forms of myoglobin. They are deoxymyoglobin and oxymyoglobin. Deoxymyoglobin is the form that lacks oxygen whereas oxymyoglobin is bounded to oxygen. Myoglobin functions as an oxygen storage protein rather than oxygen transport protein because it has very strong affinity for oxygen. Also its structure helps prevent superoxide (O2-) from leaving the heme group. Superoxide can be very detrimental to biological activity in two ways. First it can be damaging to biological materials and second it can prevent myoglobin from binding to oxygen by turning the iron state from Fe2+ to Fe3+. The state where the iron is in Fe3+ is called metmyoglobin. In order to prevent oxygen leaving as a superoxide, myoglobin has an additional histidine residue which forms hydrogen bond with the oxygen molecule. Unlike hemoglobin which is found in the red blood cells, myoglobin is found in muscle tissues.
Hemoglobin is an iron-containing protein in the red blood cells that is responsible for the transport of oxygen from the respiratory organs (i.e. lungs) to the rest of the body (i.e. the tissues). Unlike myoglobin which consists of a single polypeptide chain, hemoglobin consists of 4 polypeptide chains. Two identical chains are denoted as alpha chains where the other two identical chains are denoted beta chains. The four chains bind to oxygen cooperatively meaning that the binding of one oxygen in one site increases the affinity for oxygen in the other sites of hemoglobin. The picture below shows the structure of hemoglobin. Protein is a macromolecule.
Oxygen Binding CurveEdit
Oxygen binding curve (OBC) shows oxygen-binding capacity of oxygen binding protein. The y axis of the OBC shows the fractional saturation level. The fractional saturation is the fraction in which the binding site is bound to oxygen. For example if the fractional saturation is 1.0 it means that all sites of the hemoglobin are bounded to oxygen where as 0.0 states that none of site of the hemoglobin is bounded to oxygen. The x-axis shows the concentration of Oxygen measured as partial pressure of Oxygen (PO2). Unit of measurement is torr. The higher the partial pressure of the oxygen the greater amount of protein molecules will be bound to oxygen. This means that the more oxygen available, the higher the chance that myoglobin will be able to bind to oxygen. The oxygen binding curve of myoglobin shows that half of the myoglobin molecules are bounded to oxygen at oxygen’s partial pressure of two.
Hemoglobin’s oxygen binding curve is very different that of myoglobin. Instead of bow-curving like myoglobin, hemoglobin’s curve is shaped as an S. This function is calling the sigmoid function. The sigmoid function is due to the cooperative binding behavior of hemoglobin. The graph below shows the differences between myoglobin and hemoglobin oxygen binding curve.
Hemoglobin is found in red blood cells. The red blood cells also contain a molecule known as 2, 3-bisphosphoglycerate, which interacts with hemoglobin and has the ability to reduce its affinity for oxygen, explaining hemoglobin's lower affinity for oxygen compared to that of myoglobin.
Cooperativity of HemoglobinEdit
Cooperativity of Hemoglobin is described as when one site is bounded to oxygen, the other sites will increase their affinity for oxygen. Also, if one site releases its oxygen, the other sites will decrease their affinity of oxygen and release the bounded oxygen. Cooperative charactistic of hemoglobin makes this protein a good choice for oxygen transportation. For instant when hemoglobin travel to the lung (PO2 at 100 torr) , 98% of the oxygen binding sites are occupied. As the hemoglobin travels to the tissue (P O2 at 20 torr) there is 32 percent of the oxygen binding site are occupied this mean that (98-32=66) 66% percent of the oxygen binding sites have released their oxygen. For myoglobin, 98% of oxygen binding sites are occupied in the lung but when it reaches to tissue 91% of the oxygen binding sites are occupied. This means that 7% of the oxygen binding site has released their oxygen. Although myoglobin is good at obtaining oxygen from the lung it is not efficient in releasing the oxygen to the tissue. The only case where it will give up its’ oxygen is when the oxygen concentration is extremely low. The graph below shows the percentage of oxygen delivery from the lung to the tissue of myoglobin and hemoglobin.
Cooperativity of hemoglobin can be explained by several models. Jacques Monod, Jeffries Wyman, and Jean-Pierre Changeux proposed the MWC model, also known as the converted model, in which the molecule existed in two states, the R state and the T state. The equilibrium of the two states is dependent on the binding of the oxygen. R state is exclusively of oxyhemoglobin, and T state is made up of deoxyhemoglobin. The equilibrium is shifted toward R states as more and more hemoglobin are bound to oxygen, also increasing the affinity for oxygen at this state.
Another model used to explain the cooperativity of hemoglobin is the sequential model, which disregards the idea of shifting equilibrium between R and T states caused by binding or unbinding of the ligand. This model suggests that when oxygen binds to one of the sites of the assembly of hemoglobin, the affinity for oxygen of the neighboring sites would be increased without inducing any conversion of T into R states.
The structure and functions of the hemoglobin made significant contributions to medical technology today. Iron ions moving into the plain of porphyrin causes a change in the eletronic structure of heme, which is paralleled by alterations in hemoglobin's magnetic properties. Together, these changes form the basis for functional magnetic resonance imaging (fMRI), and noninvasive method for examining brain functions. By using proper techniques, fMRI has the ability to detect differences in the relative amounts of deoxy- and oxyhemoglobin, which is indicative of brain activity. The active parts of the brain would relax its blood vessels to allow more flow of blood rich in oxyhemoglobin.