1. The shape of hemoglobin binding curves is: hyperbolic or sigmoidal 2. a) Based on the binding curves, determine the dissociation constant (Kd) for each hemoglobin complex. (Show correct units.) Kd of HbF + BPG: ________________ Kd of HbA + BPG: _____________________ b) Which has a higher affinity for oxygen? HbF+BPG HbA+BPG 3. a) How many BPG molecule(s) is/are expected to bind one hemoglobin complex? 1 2 3 4 b) BPG binding preferentially stabilizes which state of hemoglobin? T R c) BPG binds to the oxygen binding site in hemoglobin. This statement is: True False d) BPG binding reduces hemoglobin’s affinity for oxygen. This statement is: True False
The hemoglobin in the fetus (HbF) is a structural variant of the hemoglobin in the mother (HbA). HbA is a tetrameric protein complex consisting of two α-globin and two β-globin subunits. HbF is made up of two αglobin and two γ-globin subunits, where the γ-globins are similar to the β-globins but γglobins have lower affinity for 2,3- bisphosphoglycerate or BPG. Studies of oxygen transport in pregnant mammals show that the oxygen-saturation curves between the red blood cells of the fetus and the mother are markedly different.
1. The shape of hemoglobin binding curves is: hyperbolic or sigmoidal
2. a) Based on the binding curves, determine the dissociation constant (Kd) for each hemoglobin complex. (Show correct units.) Kd of HbF + BPG: ________________ Kd of HbA + BPG: _____________________ b) Which has a higher affinity for oxygen? HbF+BPG HbA+BPG
3. a) How many BPG molecule(s) is/are expected to bind one hemoglobin complex? 1 2 3 4
b) BPG binding preferentially stabilizes which state of hemoglobin? T R
c) BPG binds to the oxygen binding site in hemoglobin. This statement is: True False
d) BPG binding reduces hemoglobin’s affinity for oxygen. This statement is: True False
4. Compared to the β-globins in HbA, the γ-globins in HbF have a mutation that reduces their binding to BPG. How does the mutation in HbF explain the difference in oxygen-binding affinities between HbF+BPG and HbA+BPG?
5. Explain the physiological importance of the differences in oxygen affinity between fetal and maternal hemoglobin in the placenta. (Hint: how is oxygen supplied to the fetus?)
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8
0.5
0
I
2
HbF
+BPG
HbA
+BPG
4
6
p0₂ (kPa)
8
Source: Nelson, D.
ed.. MacMillan, 2017.
10
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