Question

T his is a conceptual problem that stresses the following idea: one large "molecule", Hb, exists in 2 different ormations that bind with different affinities 4 different species, H', o2, CO2 and BPG (among many others). ferential binding to T or R shifts the equilibrium. If the shift increases [T], there will be less O2 bound to Hb; if the shift increases [R], there will be more o, bound to Hb. O2 binds preferentially to the R conformation R BPG binds only to the T conformation H binds preferentially to the T conformation CO2 binds preferentially to the T conformation Example: H' binds pref. to the T conformation, shifting the equilibrium to the T form, which has low affinity for oxygen. What is the effect of the following changes on the 02 affinity of Hb? (Please justify all your answers as concisely as possible)

b. A decrease in pCO, in the lungs from 6 kPa (holding one's breath) to 2 kPa (normal).

c. An increase in the BPG level from 5 mM (normal altitude) to 8 mM (high altitude)

Answer 1

We are considering the equilibrium

R-Hb <======> T-Hb

b) The partial pressure of a gas is directly proportional to the amount of the gas (in moles). Consequently, when the partial pressure of CO₂, P(CO₂), drops, we have a lower amount of CO₂ in the lungs. Since CO₂ preferentially binds to the T-conformation, hence, a decrease in P(CO₂) lowers the percentage of T-conformation and increases the percentage of R-conformation. This is due to the fact, that in the absence of stabilization by binding with CO₂, the T-conformation converts to the more stable R-conformation (R-conformation doesn’t need binding with CO₂ to achieve extra stabilization). Therefore, more O₂ binds to the R-conformation, i.e, the affinity of R-Hb for O₂ increases.

c) BPG binds only to the T-conformation. When the BPG concentration increases, the relative percentage of the T-conformation increases due to binding with BPG. Thus, the percentage of R-Hb decreases, resulting in a decrease in the O₂-binding ability of Hb.