Fundamentals of Biochemistry

Donald Voet, Judith G. Voet, Charlotte W. Pratt

Chapter 7

Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies - all with Video Answers

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Chapter Questions

Problem 1

Estimate $K$ from the following data describing ligand binding to a protein.
$$\begin{array}{lc}\hline[\text { Ligand }](\mathrm{mM}) & Y \\\hline 0.25 & 0.30 \\\hline 0.5 & 0.45 \\\hline 0.8 & 0.56 \\\hline 1.4 & 0.66 \\\hline 2.2 & 0.80 \\\hline 3.0 & 0.83 \\\hline 4.5 & 0.86 \\\hline 6.0 & 0.93 \\\hline\end{array}$$

Shazia Naz

Shazia Naz

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Problem 2

Which set of binding data is likely to represent cooperative ligand binding to an oligomeric protein?
$$\begin{array}{lccc}\hline \text { (a) }{ [Ligand] }(\mathrm{mM}) & Y & \text { (b) } & \text { [Ligand] }(\mathrm{mM}) & Y \\
\hline 0.1 & 0.3 & 0.2 & 0.1 \\
\hline 0.2 & 0.5 & 0.3 & 0.3 \\
\hline 0.4 & 0.7 & 0.4 & 0.6 \\
\hline 0.7 & 0.9 & 0.6 & 0.8 \\
\hline\end{array}$$

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Problem 3

Use Eq. $7-8$ to estimate the fractional saturation of hemoglobin when $p \mathrm{O}_{2}$ is
(a) 20 torr, $(b) 40$ torr, and
(c) 60 torr.

Rashmi Gondi

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Problem 4

Calculate the $p_{\text {so }}$ value for hemoglobin if $Y_{\mathrm{O}_{2}}=0.82$ when $p \mathrm{O}_{2}=$ 25 torr.

Mena Botros

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Problem 5

Drinking a few drops of a commercial preparation called "vitamin O." which consists of oxygen and sodium chloride dissolved in water. is claimed to increase the concentration of oxygen in the body, (a) Use your knowledge of oxygen transport to evaluate this claim.
(b) Would vitamin O be more or less effective if it were infused directly into the bloodstream?

Mena Botros

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Problem 6

Explain why long-distance runners prefer to train at high altitude even when the race is to be held at sea level. Why must the runners spend more than a day or two at the higher elevation?

Crystal Wang

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Problem 7

Is the $p_{50}$ higher or lower than normal in (a) hemoglobin Yakima and (b) hemoglobin Kansas? Explain.

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Problem 8

In hemoglobin Rainier, Tyr $145 \beta$ is replaced by Cys, which forms a disulfide bond with another Cys residue in the same subunit. This prevents the formation of ion pairs that normally stabilize the T state. How does hemoglobin Rainier differ from normal hemoglobin with respect to
(a) oxygen affinity,
(b) the Bohr effect, and
(c) the Hill constant?

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Problem 9

Hemoglobin S homozygotes who are severely anemic often have elevated levels of BPG in their erythrocytes. Is this a beneficial effect?

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Problem 10

In the variant hemoglobin $C$, glutamate at position 6 of the $\beta$ chain has been replaced with lysine. (a) Would you expect this mutant hemoglobin to polymerize as hemoglobin S does? (b) Red blood cells containing hemoglobin C have a shorter lifespan than red blood cells containing normal hemoglobin. How might this affect a person's resistance to malaria?

Crystal Wang

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Problem 11

Is myosin a fibrous protein or a globular protein? Explain.

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Problem 12

In striated muscle, cells undergo mitosis (nuclear division) without cytokinesis (cellular division), giving rise to large multinucleate cells. Explain why muscle cells would be less effective if cytokinesis occurred with every round of mitosis.

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Problem 13

A myosin head can undergo five ATP hydrolysis cycles per second, each of which moves an actin monomer by $\sim 100$ A. How is it possible for an entire sarcomere to shorten by 1000 A in this same period?

Shazia Naz

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Problem 14

Rigor mortis, the stiffening of muscles after death, is caused by depletion of cellular ATP. Describe the molecular basis of rigor.

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Problem 15

The force generated by a muscle fiber increases as the sarcomere shortens but decreases at very short sarcomere lengths. Explain this observation. (Hint: Recall that cell volume remains constant during muscle contraction.)

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Problem 16

Antibodies are well suited for recognizing extracellular substances from invading bacteria and viruses. However, the immune system must also be able to respond to intracellular infections. Explain why the immune system includes binding proteins that recognize F-actin.

Mena Botros

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Problem 17

Give the approximate molecular masses of an immunoglobulin $G$ molecule analyzed by (a) gel filtration chromatography, (b) SDS-PAGE, and (c) SDS-PAGE in the presence of 2-mercaptoethanol.

Rabeya Zahid

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Problem 18

Many fish produce a tetrameric IgM. If each H chain has a mass of $70 \mathrm{kD},$ each light chain has a mass of $25 \mathrm{kD},$ and each $\mathrm{J}$ chain has a mass of $15 \mathrm{kD},$ what is the approximate mass of the IgM molecule?

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Problem 19

Explain why the variation in $\mathrm{V}_{\mathrm{L}}$ and $\mathrm{V}_{\mathrm{H}}$ domains of immunoglobulins is largely confined to the hypervariable loops.

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Problem 20

How many hypervariable loops are present in (a) IgG and (b) IgM?

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Problem 21

In active muscles, the $p \mathrm{O}_{2}$ may be 10 torr at the cell surface and 1 torr at the mitochondria (the organelles where oxidative metabolism occurs). Use Eq. $7-6$ to show how myoglobin $\left(p_{50}=2.8 \text { torr }\right)$ facilitates the diffusion of $\mathrm{O}_{2}$ through these cells.

Rabeya Zahid

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Problem 22

If myoglobin had the same $p_{50}$ value as hemoglobin, how well would it facilitate $\mathrm{O}_{2}$ diffusion under the conditions described in Problem $21 ?$

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Problem 23

Some primitive animals have a hemoglobin that consists of two identical subunits. Sketch an oxygen-binding curve for this protein.

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Problem 24

What is the likely range of the Hill constant for the hemoglobin described in Problem $23 ?$

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Problem 25

In humans, the urge to breathe results from high concentrations of $\mathrm{CO}_{2}$ in the blood; there are no direct physiological sensors of blood $p \mathrm{O}_{2}$ Skindivers often hyperventilate (breathe rapidly and decply for several minutes) just before making a dive in the belief that this will increase the $\mathrm{O}_{2}$ content of their blood.
(a) Does it do so?
(b) Use your knowledge of hemoglobin function to evaluate whether this practice is useful.

Shazia Naz

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Problem 26

The crocodile, which can remain under water without breathing for up to $1 \mathrm{h}$, drowns its air-breathing prey and then dines at its leisure. An adaptation that aids the crocodile in doing so is that it can utilize virtually $100 \%$ of the $\mathrm{O}_{2}$ in its blood, whereas humans, for example, can extract only $-65 \%$ of the $\mathrm{O}_{2}$ in their blood. Crocodile $\mathrm{Hb}$ does not bind BPG. However, crocodile deoxyHb preferentially binds $\mathrm{HCO}_{3}^{-}$. How does this help the crocodile obtain its dinner?

Shazia Naz

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Problem 27

An anemic individual, whose blood has only half the normal Hb content, may appear to be in good health. Yet a normal individual is incapacitated by exposure to sufficient carbon monoxide to occupy half of his/her heme sites $(p \mathrm{CO} \text { of } 1 \text { torr for } \sim 1 \mathrm{h} ; \mathrm{CO} \text { binds to } \mathrm{Hb}$ with 200 -fold greater affinity than does $\mathrm{O}_{2}$ ). Explain.

Shazia Naz

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Problem 28

When you hold a weight at arm's length, you are not doing any thermodynamic work but the muscles supporting the weight are nevertheless consuming energy. Describe, on the molecular level, how muscles might maintain such state of constant tension without contracting. Why does this state consume ATP?

Shazia Naz

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Problem 29

Explain why a microfilament is polar, whereas a filament of keratin is not.

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Problem 30

Cells contain an assortment of proteins that promote microfilament disassembly during cell shape changes. How can such proteins distinguish newly synthesized microfilaments from older microfilaments?

Rabeya Zahid

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Problem 31

Why do antibodies raised against a native protein sometimes fail to bind to the corresponding denatured protein?

Shazia Naz

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Problem 32

Antibodies raised against a macromolecular antigen usually produce an antigen-antibody precipitate when mixed with that antigen. Explain why no precipitate forms when
(a) Fab fragments from those antibodies are mixed with the antigen; (b) antibodies raised against a small antigen are mixed with that small antigen; and (c) the antibody is in great excess over the antigen and vice versa.

Rabeya Zahid

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Problem 33

Some bacteria produce proteases that can cleave the hinge region of IgA molecules without affecting antigen binding. Explain why these proteases would give the bacteria a better chance of starting an infection.

Rabeya Zahid

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Problem 34

Individuals with the autoimmune disease systemic lupus erythematosus (SLE) produce antibodies to DNA and phospholipids.
(a) Explain why normal individuals do not make antibodies to these substances.
(b) During a normal response to a viral or bacterial infection, the immune system produces large amounts of antigen-specific antibodies, and the resulting antigen-antibody complexes are subsequently removed from the circulation and degraded. Explain why antigen-antibody complexes accumulate in the tissues of individuals with SLE.

Crystal Wang

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