Chapter 2

Sickle cell anemia results from a substitution of a valine for a glutamic acid. What do you expect the effect might be if the mutation were to have placed a leucine at that site? An aspartic acid?

Of the following amino acids, glycine, isoleucine, and lysine, which would you expect to be the most soluble in an acidic aqueous solution? Which the least?

How many structural isomers could be formed from a molecule with the formula \(\mathrm{C}_{5} \mathrm{H}_{12}\) ? \(\mathrm{C}_{4} \mathrm{H}_{8}\) ?

Glyceraldehyde is the only three-carbon aldotetrose, and it can exist as two stereoisomers. What is the structure of dihydroxyacetone, the only ketotriose? How many stereoisomers does it form?

Bacteria are known to change the kinds of fatty acids they produce as the temperature of their environment changes. What types of changes in fatty acids would you expect as the temperature drops? Why would this be adaptive?

In the polypeptide backbone \(-\mathrm{C}-\mathrm{C}-\mathrm{N}-\mathrm{C}-\mathrm{C}-\mathrm{N}-\mathrm{C}-\) \(\mathrm{C}-\mathrm{NH}_{2}\), identify the \(\alpha\) -carbons.

Which of the following are true? Increasing the pH of a solution would (1) suppress the dissociation of a carboxylic acid, (2) increase the charge on an amino group, (3) increase the dissociation of a carboxylic acid, (4) suppress the charge on an amino group.

Which of the four classes of amino acids has side chains with the greatest hydrogen-bond-forming potential? Which has the greatest potential to form ionic bonds? Hydrophobic interactions?

If the three enzymes of the pyruvate dehydrogenase complex existed as physically separate proteins rather than as a complex, what effect might this have on the rate of reactions catalyzed by these enzymes?

Would you agree that neither ribonuclease nor myoglobin had quaternary structure? Why or why not?

The side chains of glutamic acid (pK 4.3 ) and arginine (pK 12.5) can form an ionic bond under certain conditions. Draw the relevant portions of the side chains and indicate whether or not an ionic bond could form at the following: \((\mathrm{a}) \mathrm{pH} 4\) (b) \(\mathrm{pH} 7 ;(\mathrm{c}) \mathrm{pH} 12 ;(\mathrm{d}) \mathrm{pH} 13\)

Would you expect a solution of high salt to be able to denature ribonuclease? Why or why not?

You have read in the Human Perspective that (1) mutations in the \(P R N P\) gene can make a polypeptide more likely to fold into the \(\operatorname{Pr} P^{S c}\) conformation, thus causing \(\mathrm{CJD}\) and (2) exposure to the \(\operatorname{Pr} \mathrm{P}^{\mathrm{S}}\) prion can lead to an infection that also causes \(\mathrm{CJD}\). How can you explain the occurrence of rare sporadic cases of the disease in persons who have no genetic propensity for it?

In the words of one scientist: "The first question any structural biologist asks upon being told that a new [protein] structure has been solved is no longer "What does it look like?; it is now What does it look like ? "What do you suppose he meant by this statement?

It was noted in the Human Perspective that persons with arthritis who had taken certain NSAIDs over a long period of time crhibited a lower incidence of Alzheimer's disease, yet doubleblinded clinical trials on these same drugs did not appear to benefit patients with AD. These would appear to be contradictory findings. The first type of study is referred to as a retrospective study in that researchers look backwards from a correlation that is made at the present time, in this case a conclusion that taking NSAIDs over a period of time may prevent the development of AD. The second type of study is referred to as a prospertive study in that it looks forward to future results based on an experimental plan to give some patients a drug and others a placebo. Can you give a reason why these two different approaches might lead to differing conclusions about the use of these drugs?