Chapter 9

1. Complete the interactive matching exercise to see answers.

2. 1. 2.96 × 10⁻¹¹ g

   2. 2.71 × 10⁸ molecules

   3. No. There would be 3.22 × 10⁸ hemoglobin molecules in a red cell if they were packed in a cubic crystalline array. Hence, the actual packing density is about 84% of the maximum possible.

3. 2.65 g (4.75 × 10⁻² mol) of Fe

4. 1. In human beings, 1.44 × 10⁻² g (4.49 × 10⁻⁴ mol) of O₂ per kilogram of muscle. In sperm whales, 0.144 g (4.49 × 10⁻³ mol) of O₂ per kilogram.

   2. 128

5. The cooperativity allows hemoglobin to become saturated in the lungs, where oxygen pressure is high. When the hemoglobin moves to tissues, the lower oxygen pressure induces it to release oxygen and thus deliver oxygen where it is needed. Thus, the cooperative release favors a more complete unloading of oxygen in the tissues.

6. Deoxyhemoglobin is in the T state. The presence of oxygen disrupts the R ⇌ T equilibrium in favor of the R state. The structural changes are significant enough to cause the crystal to come apart.

7. Hemoglobin with oxygen bound to only one of four sites remains primarily in the T-state quaternary structure, an observation consistent with the sequential model. On the other hand, hemoglobin behavior is concerted in that hemoglobin with three sites occupied by oxygen is almost always in the quaternary structure associated with the R state.

8. Fetal hemoglobin does not bind 2,3-BPG as well as maternal hemoglobin does. Recall that the tight binding of 2,3-BPG by hemoglobin reduces the oxygen affinity of hemoglobin.

9. Hemoglobin S molecules bind together to form large fibrous aggregates that extend across the cell, deforming the red blood cells and giving them their sickle shape. This aggregation takes place predominantly in the deoxygenated form of Hb S. Small blood vessels are blocked because of the deformed cells, which creates a local region of low oxygen concentration. Hence, more hemoglobin changes into the deoxy form and so more cells undergo sickling. Sickled red cells become trapped in the small blood vessels, impairing circulation and leading to the damage of many tissues. Sickled cells, which are more fragile than normal red blood cells, rupture (hemolyze) readily to produce severe anemia.

10. Deoxyhemoglobin A contains a complementary site, and so it can add to a fiber of deoxyhemoglobin S. The fiber cannot then grow further, because the terminal deoxy Hb A molecule lacks a sticky patch.

11. The whale swims long distances between breaths. A high concentration of myoglobin in the whale muscle maintains a ready supply of oxygen for the muscle between breathing episodes.

12. The presence of 2,3-BPG shifts the equilibrium toward the T state. 2,3-BPG binds only to the center cavity of deoxyhemoglobin (T state). The size of the center cavity decreases on the change to the R form, expelling the 2,3-BPG and thus facilitating the formation of the R state.

13. A higher concentration of 2,3-BPG would shift the oxygen-binding curve to the right. The rightward shift of the oxygen-binding curve would promote the dissociation of oxygen in the tissues and would thereby increase the percentage of oxygen delivered to the tissues.

14. 1. The transfusion would increase the number of red blood cells, which increases the oxygen-carrying capacity of the blood, allowing more sustained effort.

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    2. BPG stabilizes the T state of hemoglobin, which results in a more efficient release of oxygen. If BPG is depleted, the oxygen will not be released even though the red blood cells are carrying more oxygen.

15. The Bohr effect, not to be confused with the boring effect of a monotonous lecture, is the regulation of hemoglobin oxygen binding by hydrogen ions and carbon dioxide. Deoxyhemoglobin is stabilized by ionic bonds that stabilize the T state. One of these bonds forms between carboxyl-terminal His β146 and Asp β94. As the pH increases, this stabilizing salt bridge is broken because His β146 becomes deprotonated and loses its positive charge, facilitating the formation of the R state. At lower pH values, His β146 is positively charged. The formation of the ionic bonds shifts the equilibrium from the R state to the T state, thus releasing oxygen.

16. Oxygen binding appears to cause the copper ions, along with their associated histidine ligands, to move closer to each other, thereby also moving the helices to which the histidines are attached (in similar fashion to the conformational change in hemoglobin).

17. Inositol pentaphosphate in part c. Inositol pentaphosphate has negative charges, similarly to 2,3-BPG.

18. Complete the interactive matching exercise to see answers.

19. The electrostatic interactions between 2,3-BPG and hemoglobin would be weakened by competition with water molecules. The T state would not be stabilized.

20. (a) k_off = k_on, K = 20 s⁻¹. (b) Mean duration is 0.05 s (the reciprocal of k_off).

21. The pK_a is (a) lowered; (b) raised; and (c) raised.

22. The tight binding of carbon monoxide forces the tetramer into the R state even under oxygen partial pressures that should lead to the release of oxygen. In essence, the bound carbon monoxide shifts the oxygen saturation curve to the left.

23. 62.7% oxygen-carrying capacity

24. The modified hemoglobin would not show cooperativity. Although the imidazole in solution will bind to the heme iron atom (in place of histidine) and will facilitate oxygen binding, the imidazole lacks the crucial connection to the particular a helix that must move so as to transmit the change in conformation.

25. The release of acid will lower the pH. A lower pH promotes oxygen dissociation in the tissues. However, the enhanced release of oxygen in the tissues will increase the concentration of deoxyhemoglobin, thereby increasing the likelihood that the cells will sickle.