Notes:
An allosteric regulator is a molecule other than the ligand that can affect binding affinity. There are two types, allosteric activators and inhibitors. Allosteric activators bind and cause an increase in affinity for the ligand. Conversely, allosteric inhibitors bind and caused a decrease in affinity for the ligand.
Example:
100% oxygenated hemoglobin in the lungs is meant to make its way to tissues and deliver oxygen. However, due to how tight the oxygen is bound, only about 8% of it gets delivered. To solve this problem, the affinity for oxygen must be decreased.
2,3 BPG is an allosteric inhibitor of hemoglobin. In its presence, the p50 of hemoglobin moves to the right, meaning it has a lower affinity for O2. This makes it easier for O2 to be delivered to the tissues, as now there is not such a high affinity. Now, 66% of the oxygen is delivered to the tissues.
Additionally, the Bohr effect aids in delivering oxygen to the tissues. Actively metabolizing tissues produce CO2 and H+ which results in the pH becoming more acidic. This lower pH makes the affinity for O2 decrease, allowing even more oxygen to be delivered to tissues. In fact, now 88% of oxygen is delivered.
2,3 BPG only binds to a pocket of the T-state. Due to random fluctuations, the T-state will still occur even when oxygen is bound. When it stabilizes the T-state, oxygen will lose affinity.
CO2 binds to the N-terminus of hemoglobin, forming carbonate.
The low pH protonates side chains, stabilizing the deoxygenated form of hemoglobin, causing O2 to pop off.
All of these stabilize the T-state!!