Hemoglobin
From MyMCAT
Contents |
Introduction
Hemoglobin is the oxygen carrying protein found in red blood cells. It is responsible for the transport of oxygen from the lungs to the tissues of the body and carbon dioxide from the tissues to the lungs.
Structure
Hemoglobin is composed of four polypetide subunits and four heme groups. Each subunit, or globin, is bound to a single heme group which sits at its center in a hydrophobic pocket. At the center of the heme group lies a single iron atom (in the ferrous, 2+ state). It is this charged iron ion which binds oxygen reversibly and makes oxygen transport in the blood possible.
Typically, the four globin subunits are comprised of two alpha subunits and two beta subunits. One alpha and one beta form a tight dimer, and two of these dimers then assemble to form the complete tetramer. While the alpha subunits are found in ALL forms of hemoglobin, some variation exist in the second subunit. Beta is the most typical, however gamma, delta, and even fetal subunits are possible.
Structure and Function
The unique tetramer organization is key to proper function of the hemoglobin molecule. Hemoglobin can exist in two states, the T-state (taut) and the R-state (relaxed). In the T-state, the complex is deoxygenated and has a relatively low affinity for O2. In the R-state, it is oxygenated and has a high affinity for O2. When hemoglobin enters the lungs, the high PO2 facilitates hemoglobin accepting O2, and once O2 has been incorporated into one of the subunit's heme groups, further conformational changes make it easier for the remaining heme groups to accept O2. This phenomenon (cooperativity) is triggered by chemical and mechanical changes in the structure of the subunits which break inter-subunit disulfide bridges, relaxing the molecule and increasing the affinity for O2. In the peripheral tissues, reverse effect also occurs. Release of O2 in one subunit triggers O2 in the other subunits increasing the amount of O2 that is given to the tissues.
As a consequence of this cooperative association and dissociation, the affinity of hemoglobin for O2 is not linearly proportional to the partial pressure of O2, rather it is sigmoidal.
The Oxygen Dissociation Curve
A common requirement of the MCAT is to understand oxygen dissociation curves. If one plots the percent O2 saturation against the Partial Pressure of O2 they will observe the previously described sigmoid graph. To understand this graph there are a few key points that must be considered. At Po2 of ~80mmHg or higher, hemoglobin is essential >99% saturated with O2. This flat plateau essentially tells us that at partial pressures of O2 around normal atomspheric conditions (or even at high altitude) hemoglobin binds O2 extremely well and will become fully saturated. At partial pressures less than ~60mmHg we see a dramatic decrease in oxygen affinity. That is, at increasingly lower concentrations of O2which are typical for the peripheral tissues of the body, hemoglobin releases O2 more readily.
This process is ideal for a red blood cell. When the cell is in the lungs, the partial pressure of O2 is high and we want the hemoglobin to become fully saturated with O2. When the red blood cell enters the tissues however, we want the reverse to occur, that is, we want hemoglobin to lose its O2 affinity and release it to the nearby tissues.
