Question

2,3 BPG is quite abundant in red blood cells (~4.5 mM) and it modulates the affinity of hemoglobin for oxgen. Briefly explain what BPG is doing to the affinity of hemoglobin for oxygen.

Answer 1

2,3-BPG binds to hemoglobin in the center of the tetramer to stabilize the T state (E.g. in muscle tissues).

2,3-BPG is also extremely important in the role of stabilizing the T state of hemoglobin. The hemoglobin wants to change into a more favorable R state due to the fact that the T state is quite unstable. Pure hemoglobin (without 2,3-BPG) was tested and found to bind oxygen much more vigorously than hemoglobin in blood. A hemoglobin with 2,3-BPG has a lower affinity for oxygen binding in the tissue which allows it to be a better oxygen transporter than a pure hemoglobin, which does not have 2,3-BPG. When 2,3 BPG is present, it transports about 66% of oxygen while the pure hemoglobin only transports about 8%. The reason is that the 2,3-BPG binds inside of the hemoglobin and somehow stabilizes its T state (the state that has less affinity for oxygen). When enough oxygen has bonded to hemoglobin, a transition occurs from the T state to the R state, which releases the 2,3-BPG. 2.3-BPG stays in the hemoglobin until enough oxygen has come to replace it. This keeps the oxygen in its T state until it is ready to transition to the R state (where its affinity for oxygen increases dramatically). This broadens hemoglobin's oxygen saturation curve.

When the oxygen binds to Hemoglobin, the iron in the Heme group moves from the outside to the inside of the plane. In doing so, the Histidine side group also changes its alpha helix when the iron moves. Thus, this triggers the carbonyl terminal of the alpha helix to change position and that favors transition from T state to R state.

2,3-Bisphosphoglycerate (2,3-BPG) or 2,3-diphosphoglycerate (2,3-DPG) binds to deoxyhemoglobin with larger bonding affinity, such that it makes the T state of hemoglobin protein more stable or increases oxygen affinity of the protein; its biological function is to control bonding between hemoglobin and oxygen molecules for oxygen to be released to body tissues.

This allosteric effector binds to a site on the tetramer that is only present on the Tense(T) form of hemoglobin. The site is in the form of a pocket which is bordered by beta subunits. These positively charged subunits, His143, Lys82, and His2, interact with 2,3-BPG holding it in place. When the equilibrium of the tense form is pushed to the relaxed(R) form, the bonds that hold the 2,3-BPG molecule in place are broken and it is released. The hemoglobin stays in the T form during low concentrations of oxygen, so when 2,3-BPG is present, more of the oxygen binding sites must be filled in order for the transition from T to R form to occur.