Question

2) We discussed in class how the molecule 2,3-bisphosphoglycerate (BPG) is an inhibitor of hemoglobin (Hb). Answer the following questions about BPG and its regulation of oxygen binding:

a) Would BPG have any effect on myoglobin’s ability to bind or release oxygen? If so, describe how BPG would affect myoglobin. If not, why?

b) Based on the observation that BPG binds preferentially to partially deoxygenated Hb, briefly explain (1-2 sentences) where BPG is most likely to be most effective on Hb function within the body. How does BPG binding to Hb alter the equilibrium of oxygen binding?

c) Briefly explain how Hb function would be affected by upregulation of BPG in the blood at high altitude. What is the physiological significance of BPG upregulation with respect to the availability of oxygen at high altitude?

d) Imagine that you’re studying a mutant Hb that you made in the lab that decreases the affinity for BPG while otherwise not affecting the usual T-R equilibrium. i) Draw a standard O2 binding curve for wild-type Hb and indicate how the curve for the mutant Hb would be shifted relative to wild-type Hb. ii) Briefly explain how the mutation would affect O2 binding and release in both the lungs and peripheral tissue.

Answer 1

A). 2,3-bisphosphoglycerate (BPG) have no effect on myoglobin’s ability to bind or release oxygen because it cannot bind to myoglobin in the similar way to hemoglobin.

B). The venous blood contains partially deoxygenated hemoglobin, so 2,3-BPG most likely binds to hemoglobin in the venous blood and decreases the oxygen-binding affinity of hemoglobin by decreasing its affinity for oxygen due to alteration in conformational changes, oxygen is loosely bound to hemoglobin in the presence of BPG. So, increased levels of 2,3-BPG makes more oxygen available to cells.

C). The atmospheric pressure of oxygen decreases at high altitudes. People living at high altitudes are adapted to lower P_O2 levels. One of the key change observed in this adaptation is increased 2,3-BPG (2,3- bisphosphoglycerate), which shift P₅₀ to higher values.