Cooperative oxygen binding in haemoglobin
In cooperative binding, each oxygen that binds makes the next bind more easily, as haemoglobin moves from a tense state, which holds oxygen weakly, to a relaxed one.
Remember
Oxygen binding draws the iron atom of a haem group (a flat ring with iron at its centre) into the plane of the ring, which switches haemoglobin to its relaxed state, so every further oxygen binds more easily.
Memory aid
T is for tense, so the oxygen-free form is tight and reluctant, and R is for relaxed, so the oxygen-bound form accepts oxygen easily
The letter T stands for the tense form, which holds oxygen weakly, and the letter R for the relaxed form, which accepts oxygen easily.
Haemoglobin is a protein made of four chains, called globin chains. Each chain holds a haem group, which is a flat ring (a porphyrin ring) with an iron atom at its centre. Oxygen attaches to that iron, so one haemoglobin molecule can bind four oxygen molecules.
With no oxygen bound, haemoglobin is in the tense (T) state, which has a low affinity for oxygen. Affinity means how tightly a molecule holds on to oxygen. In this state the iron sits slightly out of the plane of the ring. When the first oxygen molecule binds, it pulls the iron into the plane of the ring. That small movement is passed through the protein, so that the whole molecule changes shape (a conformational change) and moves to the relaxed (R) state, which has a high affinity for oxygen.
In the relaxed state the remaining haem groups take up oxygen much more easily, so each further oxygen molecule binds more readily than the one before. This is cooperative binding: binding at one site makes binding at the other sites easier. It works because the four chains communicate with each other. This suits the lungs, where oxygen pressure is high and haemoglobin fills quickly. In the tissues, where the pressure is low, the process runs in reverse, so once the first oxygen has gone, the next is released more easily.
Because cooperativity depends on the chains communicating, a mutation that changes an amino acid at the interface (where the chains meet) is most likely to reduce cooperativity, even though the haem groups can still bind oxygen. Because of cooperativity, the oxygen dissociation curve (a graph of how saturated haemoglobin is at different oxygen pressures) is normally steep in its middle range, and weaker cooperation makes it less steep.
Key facts
- States
- haemoglobin has a low-affinity tense (T) form and a high-affinity relaxed (R) form.
- Trigger
- oxygen binding to the iron draws the iron atom into the plane of the porphyrin ring.
- Switch
- that movement shifts haemoglobin from the tense state to the relaxed state, and the change is reversible.
- Binding sites
- each haemoglobin molecule can bind four oxygen molecules.
- Effect on other sites
- once the first oxygen is bound, the other three haem groups bind oxygen more easily.
- Lungs and tissues
- cooperativity favours oxygen loading (haemoglobin taking up oxygen) in the lungs, where the oxygen pressure is very high, and oxygen release in the tissues, where it is very low.
Exam traps
- Having four haem groups, each with an iron atom, does not alone make binding cooperative, because four binding sites are not enough: the chains must communicate by changing shape.
- Oxygen binds to the iron in haem reversibly, not permanently, because a permanent bond would hold on to the oxygen and the tissues would receive none.
- Oxygen does not attach directly to the globin chains: it attaches to the iron in haem, while the chains hold the haem groups and change shape when oxygen binds.
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