In: Biology
With reference to the structure of hemoglobin and your knowledge
of complex
formation reactions, discuss the stability of oxygenated hemoglobin
versus
deoxygenated hemoglobin. Be sure to fully outline your
reasoning.
A haemoglobin molecule is composed of four polypeptide globin chains. Each contains a haem moiety which has an organic part (a protoporphyrin ring made up of four pyrrole rings) and a central iron ion in the ferrous state (Fe2+).
Oxygen binds reversibly to haem, so each haemoglobin molecule can carry up to four oxygen molecules.
Haemoglobin is an allosteric protein; the binding of oxygen to one haem group increases the oxygen affinity within the remaining haem groups. This ‘co-operativity’ between the component parts of haemoglobin means that oxyhaemoglobin has a substantially different quaternary structure to deoxyhaemoglobin.
Hemoglobin exists in two forms, a taut (tense) form (T) and a relaxed form (R). Various factors such as low pH, high CO2 and high 2,3 BPG at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues. Conversely, a high pH, low CO2, or low 2,3 BPG favors the relaxed form, which can better bind oxygen.
The partial pressure of the system also affects O2 affinity where, at high partial pressures of oxygen (such as those present in the alveoli), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, T) tense state is favoured.
Additionally, the binding of oxygen to the iron(II) heme pulls the iron into the plane of the porphyrin ring, causing a slight conformational shift. The shift encourages oxygen to bind to the three remaining heme units within hemoglobin (thus, oxygen binding is cooperative).
The sigmoid shape of the oxyhaemoglobin dissociation curve is due to co-operativity between the component globin chains. This means that the affinity of haemoglobin for oxygen is the lowest when the first oxygen molecule binds to the tense, deoxyhaemoglobin molecule, so at a very low partial pressure of oxygen (PO2), the gradient of the curve is almost flat. Each subsequent oxygen molecule binds to haemoglobin more easily, so the curve gradient increases. As PO2 increases further, almost all the oxygen-binding sites become occupied, so the curve levels off again. Under normal physiological circumstances, when venous oxygen saturation is 75% or above, only the final molecule of oxygen is binding and unbinding from the haemoglobin, making this a highly efficient system.
Figure shows the oxyhaemoglobin dissociation curve.
The normal curve for adult haemoglobin is shown in red, with dots showing the normal values in arterial and venous blood. P50, the PO2 at which haemoglobin is 50% saturated, is indicated by the arrow showing a normal value of 3.5 kPa. The curve can be shifted to the left or right by the factors listed below but these physiological changes in adults are small compared with the increased oxygen binding achieved by fetal haemoglobin (purple line).
The ‘P50’ is an important concept in the oxyhaemoglobin dissociation curve. It is a measure of oxygen affinity and is used to compare changes in the position of the curve. P50 is the partial pressure of oxygen in blood in which haemoglobin is 50% saturated, and a change in its value therefore describes whether the curve has shifted to the left or the right. Different forms of haemoglobin have different P50 values, for example, P50 for HbA is 3.5 kPa compared with 2.5 kPa for HbF, reflecting the higher affinity that HbF has for oxygen.
Factors that decrease the oxygen affinity of haemoglobin and therefore increase the P50
Increased temperatureI
Increasedncreased hydrogen ion concentration (lower pH)
Increased carbon dioxide partial pressure
Increased 2,3-DPG concentration
This is Bohr effect