1.  Two by two. Match each term with its description.

2.  Hemoglobin content. The average volume of a red blood cell is 87 mm³. The mean concentration of hemoglobin in red cells is 0.34 g ml⁻¹.

(a) What is the weight of the hemoglobin contained in a red cell?

(b) How many hemoglobin molecules are there in a red cell?

(c) Could the hemoglobin concentration in red cells be much higher than the observed value? (Hint: Suppose that a red cell contained a crystalline array of hemoglobin molecules in a cubic lattice with 65-Å sides.)

3.  Iron content. How much iron is there in the hemoglobin of a 70-kg adult? Assume that the blood volume is 70 ml kg⁻¹ of body weight and that the hemoglobin content of blood is 0.16 g ml⁻¹.

4.  Oxygenating myoglobin. The myoglobin content of some human muscles is about 8 g kg⁻¹. In sperm whale, the myoglobin content of muscle is about 80 g kg⁻¹.

(a) How much O₂ is bound to myoglobin in human muscle and in sperm-whale muscle? Assume that the myoglobin is saturated with O₂.

(b) The amount of oxygen dissolved in tissue water (in equilibrium with venous blood) at 37°C is about 3.5 × 10⁻⁵ M. What is the ratio of oxygen bound to myoglobin to that directly dissolved in the water of sperm-whale muscle?

5.  Cooperation is good. What is the physiological significance of the cooperative binding of oxygen by hemoglobin? ✓ 7

6.  Suddenly breaking into pieces. When crystals of deoxyhemoglobin are exposed to oxygen, the crystals shatter. Why? ✓ 7

7.  Hybrid vigor. The oxygen-binding behavior of hemoglobin displays aspects of both the sequential model and the concerted model. Explain. ✓ 7

8.  Mom to baby. What accounts for the fact that fetal hemoglobin has a higher oxygen affinity than maternal hemoglobin? ✓ 7

9.  Structural damage. How does hemoglobin S cause tissue damage?

10.  Saving grace. Hemoglobin A inhibits the formation of the long fibers of hemoglobin S and the subsequent sickling of the red cell on deoxygenation. Why does hemoglobin A have this effect?

11.  Screening the biosphere. The first protein to have its structure determined was myoglobin from sperm whales. Propose an explanation for the observation that sperm-whale muscle is a rich source of this protein.

12.  Fits in the pocket. Describe the role of 2,3-bisphosphoglycerate in the function of hemoglobin. ✓ 8

13.  High-altitude adaptation. After a person spends a day or more at high altitude (with an oxygen partial pressure of 75 torr), the concentration of 2,3-bisphosphoglycerate in that person’s red blood cells increases. What effect would an increased concentration of 2,3-BPG have on the oxygen-binding curve for hemoglobin? Explain why this adaptation would be beneficial for functioning well at high altitude. ✓ 8

14.  Blood doping. Endurance athletes sometimes try an illegal method of blood doping called autologous transfusion. Some blood from the athlete is removed well before competition, and then transfused back into the athlete just before competition.

(a) Why might blood transfusion benefit the athlete?

(b) With time, stored red blood cells become depleted in 2,3-BPG. What might be the consequences of using such blood for a blood transfusion?

15.  A bad lecture? What is the Bohr effect, and what is its chemical basis? ✓ 8

16.  I’ll have the lobster. Arthropods such as lobsters have oxygen carriers quite different from hemoglobin. The oxygen-binding sites do not contain heme but, instead, are based on two copper(I) ions. The structural changes that accompany oxygen binding are shown below. How might these changes be used to facilitate cooperative oxygen binding?

17.  Successful substitution. Blood cells from some birds do not contain 2,3-bisphosphoglycerate; instead, they contain one of the compounds in parts a through d, which plays an analogous functional role. Which compound do you think is most likely to play this role? Explain briefly. ✓ 8

(a)

(b)

(c)

(d)

18.  Leaning to the left or to the right. The adjoining illustration shows several oxygen-dissociation curves. Assume that curve 3 corresponds to hemoglobin with physiological concentrations of CO₂ and 2,3-BPG at pH 7. Which curves represent each of the following perturbations? ✓ 8



(a) Decrease in CO₂

(b) Increase in 2,3-BPG

(c) Increase in pH

(d) Loss of quaternary structure

19.  Location is everything. As shown in Figure 9.10, 2,3-bisphosphogylcerate lies in a central cavity, stabilizing the T state. What would be the effect of mutations that placed the BPG-binding site on the surface of hemoglobin? ✓ 8

20.  Release kinetics. The dissociation constant K_D for the release of oxygen from oxymyoglobin is 10⁻⁶ M, where K_D is defined as



The rate constant for the combination of O₂ with myoglobin is 2 × 10⁷ M⁻¹ s⁻¹.

(a) What is the rate constant for the dissociation of O₂ from oxymyoglobin?

(b) What is the mean duration of the oxymyoglobin complex?

21.  Tuning proton affinity. The pK_a of an acid depends partly on its environment. Predict the effect of each of the following environmental changes on the pK_a of a glutamic acid side chain. ✓ 8

(a) A lysine side chain is brought into proximity.

(b) The terminal carboxyl group of the protein is brought into close proximity.

(c) The glutamic acid side chain is shifted from the outside of the protein to a nonpolar site inside.

22.  Deadly gas. Carbon monoxide is a colorless, odorless gas that binds to hemoglobin at an oxygen-binding site. Indeed, it binds 200 times as tightly as oxygen, accounting for its toxic nature. Even if only one of the four oxygen-binding sites on hemoglobin is occupied by carbon monoxide, and the remaining three are bound to oxygen, oxygen is not released. Explain.

23.  Carrying a load. Suppose that you are climbing a high mountain and the oxygen partial pressure in the air is reduced to 75 torr. Estimate the percentage of the oxygen-carrying capacity that will be utilized, assuming that the pH of both tissues and lungs is 7.4 and that the oxygen concentration in the tissues is 20 torr.

24.  A disconnect. With the use of recombinant DNA techniques (Chapter 41), hemoglobin has been prepared in which the proximal histidine residues in both the a and the β subunits have been replaced by glycine. The imidazole ring from the histidine residue can be replaced by adding free imidazole in solution.



Would you expect this modified hemoglobin to show cooperativity in oxygen binding? Why or why not?

25.  Parasitic effect. When Plasmodium falciparum, a protozoan, lives inside red blood cells, the metabolism of the parasite tends to release acid. What effect is the presence of acid likely to have on the oxygen-carrying capacity of the red blood cells? On the likelihood that these cells will sickle? ✓ 8