ORGANIC CHEMISTRY TOPICAL: Biological Molecules Test 1

Time: 23 Minutes* Number of Questions: 18

* The timing restrictions for the science topical tests are optional. If you are using this test for the sole purpose of content reinforcement, you may want to disregard the time limit.

MCAT

DIRECTIONS: Most of the questions in the following test are organized into groups, with a descriptive passage preceding each group of questions. Study the passage, then select the single best answer to each question in the group. Some of the questions are not based on a descriptive passage; you must also select the best answer to these questions. If you are unsure of the best answer, eliminate the choices that you know are incorrect, then select an answer from the choices that remain. Indicate your selection by blackening the corresponding circle on your answer sheet. A periodic table is provided below for your use with the questions.

PERIODIC TABLE OF THE ELEMENTS

1 H 1.0 3 Li 6.9 11 Na 23.0 19 K 39.1 37 Rb 85.5 55 Cs 132.9 87 Fr (223) 4 Be 9.0 12 Mg 24.3 20 Ca 40.1 38 Sr 87.6 56 Ba 137.3 88 Ra 226.0 21 Sc 45.0 39 Y 88.9 57 La * 138.9 89 Ac 227.0 22 Ti 47.9 40 Zr 91.2 72 Hf 178.5 104 Unq (261) 58 Ce 140.1 90 Th 232.0 23 V 50.9 41 Nb 92.9 73 Ta 180.9 105 Unp (262) 59 Pr 140.9 91 Pa (231) 24 Cr 52.0 42 Mo 95.9 74 W 183.9 106 Unh (263) 60 Nd 144.2 92 U 238.0 25 Mn 54.9 43 Tc (98) 75 Re 186.2 107 Uns (262) 61 Pm (145) 93 Np (237) 26 Fe 55.8 44 Ru 101.1 76 Os 190.2 108 Uno (265) 62 Sm 150.4 94 Pu (244) 27 Co 58.9 45 Rh 102.9 77 Ir 192.2 109 Une (267) 63 Eu 152.0 95 Am (243) 64 Gd 157.3 96 Cm (247) 65 Tb 158.9 97 Bk (247) 66 Dy 162.5 98 Cf (251) 67 Ho 164.9 99 Es (252) 68 Er 167.3 100 Fm (257) 69 Tm 168.9 101 Md (258) 70 Yb 173.0 102 No (259) 71 Lu 175.0 103 Lr (260) 28 Ni 58.7 46 Pd 106.4 78 Pt 195.1 29 Cu 63.5 47 Ag 107.9 79 Au 197.0 30 Zn 65.4 48 Cd 112.4 80 Hg 200.6 5 B 10.8 13 Al 27.0 31 Ga 69.7 49 In 114.8 81 Tl 204.4 6 C 12.0 14 Si 28.1 32 Ge 72.6 50 Sn 118.7 82 Pb 207.2 7 N 14.0 15 P 31.0 33 As 74.9 51 Sb 121.8 83 Bi 209.0 8 O 16.0 16 S 32.1 34 Se 79.0 52 Te 127.6 84 Po (209) 9 F 19.0 17 Cl 35.5 35 Br 79.9 53 I 126.9 85 At (210) 2 He 4.0 10 Ne 20.2 18 Ar 39.9 36 Kr 83.8 54 Xe 131.3 86 Rn (222)

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Biological Molecules Test 1

Passage l (Questions 16) Sucrose, a disaccharide commonly employed in the food industry, easily undergoes acid-catalyzed hydrolysis to form D-glucose and D-fructose:
CH2 OH O HO HO H CH2 OH O HO O CH 2OH HO Sucrose CH2 OH O HO OH + HO OH HO
D Glucose DFructose (I)

H+

OH

CH2 OH O HO

OH

CH 2OH

Pure sucrose, distilled water, and concentrated hydrochloric acid were heated to reflux for approximately 2 hours. (The optical rotation of sucrose was measured using a polarimeter prior to heating.) The reaction mixture was then cooled to room temperature, transferred to a volumetric flask, and diluted with distilled water. The optical rotation of the product mixture was then determined. In addition, a small sample of both sucrose and the product mixture were reacted with Benedicts reagent (an aqueous solution of Na2CO3, CuSO4, and sodium citrate). Benedicts reagent is used to test for the presence of aliphatic aldehydes and is often employed to test for diabetes; a positive result is indicated by the formation of the brick-red precipitate Cu2O. The results of the experiment are as follows: Table 1 Specific rotation []D Solution before hydrolysis Solution after hydrolysis +66/5 19.9 Benedicts Test Negative Positive

Figure 1 Under acidic conditions, D-glucose undergoes mutarotation giving an equilibrium mixture of - and anomers, whereas D-fructose exists as four different isomers (isomer IV being the predominant form):
HOCH2 O HO II CH 2OH O HO III OH OH HO CH2OH OH V I OH CH 2OH HO OH OH IV O OH OH

The specific rotation for D-(+)-glucose is +52.7, while that of D-()-fructose is 92.4. 1 . In sucrose, shown below, which bond is an glucosidic linkage?
I

CH 2OH

HOCH2

O OH

CH2OH O
OH

H CH OH 2 O HO O

IV

HO

HO

OH

CH2 OH HO III II

Figure 2 A student carried out the hydrolysis of sucrose using the following procedure: A. B. C. D. I II III IV

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2 . Sucrose does NOT produce a positive test when treated with Benedicts solution because: A . the carbonyl functionalities of both subunits are involved in the formation of a glycosidic linkage. B . it undergoes mutarotation. C . the molecule is not oriented correctly for a reaction to occur. D . disaccharides do not possess free hemiacetal or hemiketal groups. 6 . Which of the following is another name for sucrose? I. II. III. IV. A. B. C. D. -D-Glucopyranosyl -D-fructofuranoside -D-Glucofuranosyl -D-fructopyranoside -D-Fructofuranosyl -D-glucopyranoside -D-Fructofuranosyl -D- glucopyranoside

I only I and III only II and III only II and IV only

3 . In the experiment, what would happen if only part of the reaction mixture was transferred to the volumetric flask? A . The observed rotation would decrease specific rotation would remain the same. B . The observed rotation and the specific would decrease. C . The observed rotation and the specific would increase. D . The observed rotation would increase specific rotation would remain the same. and the rotation rotation and the

4 . Which of the isomers shown in Figure 2 are anomers? A. B. C. D. II and III only II and IV only III and IV only III and V only

5 . The experiment described in the passage was repeated using maltose instead of sucrose. The key difference in the results was that the Benedicts test before hydrolysis was positive. This proves that: A. B. C. D. maltose contains a more reactive glycosidic bond. sucrose is a reducing sugar. sucrose will hydrolyze more readily than maltose. maltose contains a free hemiacetal group.

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Biological Molecules Test 1

Passage II (Questions 713) Aerobic organisms are defined as those that require oxygen to generate energy. Involved in this energy generating process are cytochromes: mitochondrial ironcontaining proteins that facilitate the transfer of electrons. One cytochrome that has been extensively studied is cytochrome c. This molecule consists of a polypeptide chain approximately 100 amino acids long. It folds in such a way as to allow the covalent attachment of an ironcontaining heme group. Selective hydrolysis of the protein portion of cytochrome c produces the polypeptide chain whose amino acid sequence is shown below: Gly-Asp-Val-Glu-Lys-Gly-Lys-Lys-Ile-Phe-Ile-Met-LysCys-Ser A chemist attempted to analyze the protein portion of cytochrome c by employing the Sanger method. This technique is used to identify the N-terminal amino acid residue in a polypeptide and involves the use of 2,4dinitrofluorobenzene (DNFB). In the presence of a mild base, a nucleophilic aromatic substitution reaction occurs yielding a labeled polypeptide. Subsequent hydrolysis then gives a mixture of amino acids, and the N-labeled amino acid can now be separated and identified:
O 2N NO2 2,4-Dintrofluorobenzene Polypeptide F + H2NCHCO R HNCHCO R' etc HCO 3 (HF)

When the original cytochrome c protein was treated using the Sanger method, the 2,4-dinitrophenyl derivative of glycine was observed. In addition, the cytochrome c portion shown in Figure 1 was treated with a proteolytic enzyme specific for the N-terminal end of amino acids that possess an amino side chain. Five fragments were produced in equal amounts, which were separated. purified and analyzed by electrophoresis. The results are shown below. Fragment number 1 2 3 4 5 Table 1 Molecular weight (Daltons) 418 336 203 146 650 Isoelectric point (pI) 2.92 9.62 9.74 9.74 9.74

The following data was also obtained to assist the chemist in identifying the fragments. Table 2
Name pK a COOH Glycine (Gly) Valine (Val) Glutamic acid (Glu) Aspartic acid (Asp) Lysine (Lys) Isoleucine (Ile) 2.18 2.36 1.83 8.95 9.68 9.13 10.53 146 131 165 (CH2)4NH2 CH(CH3)C2H 5 CH 2 Ph (CH2)2SCH 3 2.10 9.8 3.9 133 CH2COOH 2.34 2.32 2.19 pK a NH3+ 9.63 9.62 9.67 pK R group 4.25 Molecular weight 75 117 147 H CH(CH3)2 (CH2)2COOH R group

O 2N NO2

NHCHCO R

NHCHCO R'

etc

H 3O +

Phenylalanine (Phe) Methionine (Met) Cysteine (Cys) Serine (Ser)

2.28

9.21

149

Labeled polypeptide

1.96 2.21

10.8 9.15

8.3

121 105

CH 2SH CH2OH

O 2N NO2

+ NHCHCOOH + H 3NCHCO2 R Labeled amino acid R' Unlabeled amino acid

Reaction 1

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7 . If the fragments shown in Table 1 are subjected to electrophoresis at a pH of 4, in which direction will fragment 5 move? A. B. C. D. Toward the cathode Toward the anode It will not move The direction of migration cannot be determined without more information 1 2 . Which of the following amino acids would possess a negatively charged R group at pH 67? A. B. C. D. Aspartic acid and glutamic acid Lysine Cysteine and lysine Serine

1 3 . Which of the amino acids listed below has the most basic functional group on its side chain? 8 . Which of the following fragments are unlikely to be formed when the polypeptide in Figure l is treated with the side-chain-specific proteolytic enzyme? A. B. C. D. Lys-Gly Gly-Asp-Val-Glu Gly-Asp-Val Lys-Cys-Ser A. B. C. D. Aspartic acid Lysine Phenylalanine Glycine

9 . What is the isoelectric point of aspartic acid? A. B. C. D. 9.80 6.80 5.95 3.00

1 0 . From the data in Table 1 and 2, Fragments 1 and 2 are respectively: A. B. C. D. Gly-Lys-Lys-Lys and Phe-Ile-Met Gly-Asp-Val-Glu and Lys-Cys-Ser Lys-Gly and Lys-Cys-Ser Val-Glu and Lys-Ile-Phe-Ile-Met

1 1 . The reaction of DNFB with the polypeptide is carried out under basic conditions rather than acidic conditions because: A . it ensures that the terminal carboxyl functionality on the polypeptide is protonated and is free to react. B . it ensures that the terminal amine functionality on the polypeptide is protonated and is free to react. C . it ensures that the terminal amine functionality on the polypeptide is deprotonated and is free to react. D . it ensures that the terminal carboxyl functionality on the polypeptide is deprotonated and is free to react. GO ON TO THE NEXT PAGE.

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Biological Molecules Test 1

Questions 14 through 18 are NOT based on a descriptive passage. 1 4 . Which would be the best representation of a cross linkage in the following polypeptide: Alal-Thr-Tyr-Pro-His-Gly-Ser-Phe-Ala-Cys-Met-LysGin-Asp-Asp-Cys-Arg-Glu-Glu19
A.
1

1 7 . All of the bonds listed below are apparent in the secondary and tertiary structure of a protein EXCEPT: A. B. C. D. hydrogen bonding. hydrophobic interactions. electrostatic interactions. peptide bonds.

1 8 . Which of the following pairs of side chain R groups would tend to associate with each other?
A. CH2 and CH2OH

C.

4 N

7 O C=O 14 19

N 9
B. (CH 2) 2 COOH and CH2

19

B.

D. 1

C.

CH3 CH CH3 and

CH3 CH CH2CH3

8 NH O=C 14 19

10 S S 19
D. CH3 CH CH3 and CH2COOH

1 5 . The localized bending and folding of a polypeptide backbone in a protein molecule is usually referred to as its: A. B. C. D. primary structure. secondary structure. tertiary structure. quaternary structure.

1 6 . Which of the following bonds is a peptide linkage?

A. O C B. H NH O C O D. O C H N C O C.

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ANSWER KEY: 1. C 2. A 3. A 4. B 5. D 6. 7. 8. 9. 10. B A C D B 11. 12. 13. 14. 15. C A B D B 16. 17. 18. D D C

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Biological Molecules Test 1

BIOLOGICAL MOLECULES TEST 1 EXPLANATIONS Passage I (Questions 16) 1. The correct answer to question 1 is choice C. This question requires you to have some outside knowledge of the types of linkages found in carbohydrates, specifically where the alpha-glucosidic linkage is in sucrose. You should be able to see that in sucrose, glucose and fructose are present as glycosides. Remember that a glycoside is a carbohydrate in its acetal or ketal form, in which the anomeric hydroxyl group is replaced with an alkoxy group. This alkoxy group could be an oxygen attached to another monosaccharide or a simple alkyl group. So, in the sucrose molecule you have a glucoside sub-unit (a glucose molecule as its corresponding acetal) and a fructoside (a fructose molecule as corresponding ketal). Therefore, a glucoside bond would be one in which the glucose sub-unit is attached to an alkoxy group. You are also told that the linkage is alpha and again, if you visualize the glucose portion on its own, you should know that the alpha corresponds to the downwards or axial orientation of the hydroxyl group on the anomeric carbon. In sucrose, this hydroxyl group is replaced by an oxygen linked to fructose--confirming glucose is in the form of an acetal. In summary then, you are looking for a linkage between glucose and its acetal group which is oriented axially or downwards on the page. The only choice that fits this criteria is III, making choice C the correct response. Now for the wrong answers. Choice A is incorrect because even though this bond is present in the glucoside portion of the molecule, it is not a glucosidic linkage. This bond is simply a carbon-oxygen bond within the glucose sub-unit. Choices B and D are wrong due to the fact that they are part of the fructose sub-unit. Choice D is a carbon-carbon bond while choice B is a beta-fructoside linkage. This linkage is opposite to the alpha-glucoside linkage in that this time it's the glucose attached to the oxygen that is the ketal moiety, and this group is oriented equatorially--which is the beta position. So again, the correct answer is choice C. 2. The correct answer to question 2 is choice A. This is another question in which you really have to know your carbohydrates. This particular question has a more experimental bias because you have to know about Benedict's reagent and what it tests for. You should know that Benedict's is a common reagent used to test for reducing sugars; in other words, those sugars that contain hemiacetal or hemiketal groups. Benedict's reagent is a blue alkaline solution containing a cupric tartrate complex and when it reacts with the reducing sugar, a brick-red copper oxide precipitate is formed--characteristic of a positive test. This reaction only occurs when hemiacetals and hemiketals exist in equilibrium with their open chain forms. These open chains possess free carbonyl groups which can undergo oxidation and so reduce Benedict's. Anyway, back to the question. Sucrose doesn't give a positive Benedict's test since it doesn't possess any free carbonyl groups. Instead, these groups are tied up in forming the glycosidic bond between the two monosaccharide sub-units, so choice A is the correct answer. Choice B is incorrect as sucrose will not undergo mutarotation. As I said before, sucrose doesn't possess any free hemiacetal or hemiketal groups and the fact that it doesn't undergo mutarotation is a consequence of this. Choice C is wrong as the orientation of the molecule has nothing to do with the fact that it will not reduce Benedict's. Choice D is wrong because some disaccharides DO possess free hemiacetal and hemiketal groups. For example, maltose consists of two glucose residues, one of which is present in the hemiacetal form. Again then, choice B is the correct answer. 3. For question 3, the correct answer is choice A. Yet again, this question has an experimental bias to it, so you have to draw upon outside knowledge. You also need to know the equation commonly used in polarimetry--namely that the specific rotation is equal to the observed rotation divided by the concentration of the solution multiplied by the length of the tube. Partial transfer of the reaction mixture into the volumetric flask would result in a lower concentration of products. This would mean that the observed optical rotation would decrease--eliminating choices C and D. Since both the concentration of the product and the optical rotation decrease, the specific rotation will remain the same. This is logical if both the numerator and the denominator decrease, but looking at it from a more qualitative point of view, you should remember that for an optically active substance at a given temperature, the specific rotation only has one value. So, choice B can be eliminated and again, choice A is the correct answer. 4. The correct answer to question 4 is choice B. Alpha anomers are defined as those in which the hydroxyl group on the anomeric carbon in the ring is oriented axially. Let's take a look at each individual anomer and figure out whether they are alpha or beta in their configuration. For structures II and III, the anomeric carbon has a -CH2OH and a hydroxyl substituent attached to it. In isomer II, the hydroxyl substituent is oriented axially to the ring. Therefore, this can be classed as an alpha-anomer, and so choices C and D can immediately be eliminated. In isomer III, the hydroxyl substituent is oriented equatorial to the ring and so this is a beta anomer; choice A is out too. This leaves only choice B as the logical choice, but let's look at isomers IV and V anyway. In these, the anomeric carbon is again the one with the CH2OH and the OH group. The key difference here though is that the ring is 6-membered, not 5-membered. In isomer IV, the hydroxyl substituent is oriented axially, so it is an alpha anomer, whereas in isomer V, it

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is oriented upwards or equatorially, making it a beta-anomer, so the alpha anomers are II and IV making choice B the correct response. 5. The correct answer here is choice D. As I mentioned at the end of the explanation to question 2, maltose is a disaccharide, but it differs from sucrose in that it is a reducing sugar. Maltose is made up of two glucose sub-units, but only one of the units is a glucoside. The other sub-unit is present in the hemiacetal form, hence it can mutarotate. Mutarotation is characterized by an equilibrium between alpha and beta anomers; the conversion between these two proceeds through an open chain form which possesses a free carbonyl group that can reduce Benedict's reagent--giving the characteristic brick-red precipitate. Therefore, choice D is the correct answer as maltose contains one free hemiacetal group. Choice A is incorrect since Benedict's test has nothing to do with the glycosidic bond, so you should be able to eliminate this answer choice right away. Choice B is also incorrect because as I said before, sucrose is not a reducing sugar, due to the lack of hemiacetal and hemiketal groups. Choice C is also wrong. Although it is stating the opposite to choice A, it is still an incorrect statement because it is not relevant to the question anyway. Again, choice D is the correct answer. 6. For question 6, the correct answer is choice B. A common way to name cyclic monosaccharides is according to the ring size, and if you recall heterocyclic chemistry, you will know that pyran corresponds to a 6-membered ring, while furan corresponds to a 5-membered ring. It's logical then that a five-membered fructose ring would be a fructofuranose, while a 6-membered glucose ring would be a glucopyranose, but as I said before, the sub-units in sucrose are glycosides, so the acetal forms of glucose and fructose would be glucopyranoside and fructofuranoside. Straight away then, you can eliminate choice II, since this states that glucose will be a furanoside, not a pyranoside and that fructose will be a pyranoside, not a furanoside--so choices C and D are wrong. You should also be aware that the prefix for a glycoside is -osyl, so that fructofuranoside is fructofuranosyl and so on. Sucrose can therefore be named as a fructofuranosyl-glucopyranoside or a glucopyranosyl-fructofuranoside; statements I, III and IV are possible answer choices. The last thing to look at is the alpha and beta designations. The glucoside has an alpha linkage, while the fructoside has a beta linkage. If you can't remember this, rewind the tape to the explanations to questions 1 or 4 where I discuss these anomers in more detail. You should be able to see that choice IV is wrong, as this describes the fructofuranoside as alpha, while the glucopyranoside is beta. This confirms answer choice D as being wrong, but you could have discarded this on the strength of what we discussed earlier. As sucrose can be named as a fructofuranoside or a glucopyranoside, statements I and III are equally viable. The ring size and the anomeric designations are correct, and so choice A can be eliminated, leaving B as the correct answer. Passage II (Questions 713) 7. The correct answer here is choice A. From Table 1, you can see that the isoelectric point of fragment 5 is 9.74. The isoelectric point is defined as the point where the negative and positive charges in the amino acid cancel out, so the molecule has a zero net charge and will not move when placed in an electric field. At a pH below 9.74, the molecule will be protonated and hence positively charged, whereas at a pH higher than 9.74, the molecule will be deprotonated and so negatively charged. Since fragment 5 is in a buffer at pH 4 (which is below its isoelectric point of 9.74) it will be positively charged and so will migrate to the negatively charged electrode; namely the cathode. This makes choice A the correct response. Choice B is incorrect since the buffer would have to be at a pH above 9.74 in order for fragment 5 to migrate toward the anode. Choice C is incorrect because as I said, an amino acid that will not move when placed in an electric field is one which is at its isoelectric point. The only point which fragment 5 would be at its isoelectric point would be if the pH of the buffer was 9.74. Obviously from the question stem it isn't, so choice C can also be discarded. Finally, choice D is wrong since you can tell just from the fragment's isoelectric point and the pH of the environment which way the molecule will move. Again, choice A is the correct response. 8. The correct answer to question 8 is choice C. In order to answer this question, you need to look to the discussion of the proteolytic enzyme just before Table 1 in the passage. Here it states that the enzyme is specific for the Nterminal end of an amino acid (conventionally written on the left) which itself possesses an amino or basic side chain. Out of all of the amino acids listed, the only one that possesses an amino side chain is lysine. Therefore, we would expect the proteolytic enzyme to cleave the polypeptide at the N-terminal residue of lysine; on the left hand side. Looking at the answer choices, you can see that choice A is incorrect, since the polypeptide in Figure 1 could be cleaved between the glutamic acid and the lysine residue and the glycine and lysine residue to form the fragment shown. The fragment in choice B also forms due to cleavage of the glutamic acid-lysine linkage alone (but obviously it's an end fragment since it constitutes the first four amino acids in the polypeptide, so no other linkages have to be cleaved). As in choice B, the sequence in choice D is the end fragment of the polypeptide; more specifically the last three amino acids on the right hand side of the molecule. This can also be formed by cleavage of the methionine-lysine linkage, so D is also out. This leaves choice C as the correct response. In order to form this fragment, the enzyme would have to cleave the polypeptide at the N-terminal end of glutamic acid. This amino acid possesses a carboxyl or acidic side chain but you are told that the

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Biological Molecules Test 1

proteolytic enzyme is specific for amino acids with amino side chains, so cleavage will not occur here. Again the correct answer is choice C. 9. The correct answer here is choice D. In order to answer this question, you need to know how to calculate the isoelectric point of an amino acid from the pKa values provided. In a simple amino acid where there is only one amino group and one carboxyl group, it is relatively easy to calculate the isoelectric point; it is simply the average of the two pKa values for the amino acid; the pKa of the carboxyl group and the pKa of the protonated amino group. However, the situation starts to get a little more complex if the amino acid possesses an acidic or basic side chain. Aspartic acid indeed has an acidic side chain, so the calculation has to be adjusted to account for this. To calculate the isoelectric point, you have to look at which forms of the amino acid are involved in formation of the zwitterion. Remember that a zwitterion contains the carboxyl group in its deprotonated form and the amino group in its protonated form; these two charges cancel each other out to give a neutral molecule. Well, at low pH, the carboxyl group has to be deprotonated in order to form the zwitterion, so you certainly use the acid dissociation constant of this group. Upon increasing the pH, the zwitterion is formed. The only other proton that can now dissociate is that of the acidic side chain to produce the monoanionic form of the amino acid; therefore the acid dissociation constant of the chain also has to be used. Therefore, the isoelectric point of aspartic acid is equal to the acid dissociation constant of carboxyl group (2.1) plus the acid dissociation constant of the acidic side chain (3.9) divided by two. This gives a value of 3 which corresponds to choice D. Choice A is incorrect as this value simply corresponds to the acid dissociation constant of the NH3+ group. Choices B and C are wrong due to incorrect combinations of acid dissociation constants. Choice B is the average of the acid dissociation constants for the amino group and the carboxyl group whereas choice C is the average of the acid dissociation constants for the amino group and the acidic side chain. The pKa of the amino group is only used in the calculation if the amino acid is neutral or basic; since aspartic acid is neither one of these, choices B and C can be discarded. Again, choice D is the correct response. 10. The correct answer to question 10 is choice B. The easiest way to work out the nature of fragments 1 and 2 is to use the molecular weight data given in Table 1. Looking at choice B you can see that the molecular weight of the first fragment is equal to 418. Simply add the molecular weights of the individual amino acids (75, 133, 117, and 147) and subtract 18 for each peptide bond that is formed (as peptide bonds are formed between amino acids by a condensation reaction resulting in the loss of water). This gives you a grand total of 472 minus 54 for the peptide linkages to give a value of 418. If you apply the same method to the second fragment in choice B you get 372 minus 36 for the peptide linkages to give a total of 336. All of the other answer choices possess molecular weights that do not correspond to fragments 1 and 2 in Table 1. Again the correct answer is choice B. 11. For question 11, the correct answer is choice C. You are told that the reaction of 2,4dinitrofluorobenzene with the polypeptide proceeds through a nucleophilic aromatic substitution mechanism. You may not be too familiar with this process; electrophilic aromatic substitution is probably the reaction you have encountered. Let's look at these two different processes. Since aromatic rings are electron rich, they are susceptible to attack by species that love electrons; electrophiles. The aromatic ring consists of 6 pi electrons, arranged in a conjugated system. However, the electrons delocalize throughout the ring and so the ability of the ring to behave as isolated double bonds is lost. This means that substitution is more likely to occur over addition. The substitution versus addition property of aromatic rings is something that cannot change, but as seen in Reaction 1, the nature of the attacking species is. Here the species attacking the ring is a nucleophile; something that loves positive charges. But how can this occur when we know that the aromatic ring is electron rich? Well, you can see that not only are there two highly electron withdrawing nitro groups attached to the ring in DNFB, but there is also a fluorine attached. This means that the carbon which is attached to the fluorine has a lot of electron density pulled away from it; so much in fact that it becomes positively polarized. In other words, this carbon is susceptible to nucleophilic attack. The perfect nucleophile is the nitrogen with the lone pair of electrons at the Nterminal end of the polypeptide, which attacks the aromatic ring and substitutes the fluorine. So where does the base come in to play? Since the attacking nucleophile is the nitrogen with the lone pair, the base ensures that the terminal amine functionality remains deprotonated (in other words as NH2), so the lone pair can attack the aromatic ring: choice C is the correct response. If the reaction was carried out under acidic conditions, the amine functionality would be protonated to form NH3+. There is no lone pair on the nitrogen here; it has been used to form an additional nitrogen-hydrogen bond, so the nitrogen isn't nucleophilic anymore. Therefore, protonation of the amine functionality is out, making choice B incorrect. Choices A and D are incorrect as the terminal carboxyl functionality does not react with DNFB. Again, it is the nitrogen in the terminal amine that reacts. Again, choice C is the correct response. 12. The correct answer here is choice A. At biological pH 6 to 7, R groups which contain a carboxyl group would ionize to a carboxylate anion (if the pKa for this group is below 6). From Table 2, you can see that both aspartic and glutamic acid contain carboxyl side chains and their pKas are below 6; at biological pH, these groups will ionize to form a negatively charged R group. Choice A is the correct response. Choice B is incorrect because lysine possesses a basic side chain, and since the pKa of this group is 10.53, it would be protonated and hence positively charged at pH 6 to 7. Lysine is also included in choice C making it an incorrect response.

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Finally, choice D is incorrect since the R group for serine doesn't even possess a pKa, so you cannot tell whether it will even dissociate at pH 6 to 7. Again, choice A is the correct response. 13. The correct answer to question 13 is choice B. As I discussed in question 12, lysine has a basic side chain which has a pretty high pKa value. In other words, the protonated form of this side chain is a weak acid. This makes the free NH2 a strong base and choice B the correct response. Basic R groups are recognized by the presence of the amino group in the R group structure. Of all of the amino acids in the passage, only lysine possesses this basic side chain. Glycine has a side chain consisting of hydrogen which is definitely not as basic, so choice D is wrong. Phenylalanine possesses a side chain which isn't even polar, so C is also wrong. Finally, choice A is wrong as aspartic acid contains an acidic side chain; obviously a much weaker base than the amino side chain in lysine. Again, choice B is the correct response. Discrete Questions 14. The correct answer here is choice D. This bond is characteristic of a disulfide linkage which contributes to the primary structure of a protein. Disulfide linkages often arise due to the covalent interaction between two cysteine residues; this is the case here, where the cysteine residues numbered 10 and 16 cross link. Ester linkages such as that shown in choice A do not arise between polypeptide chains, so this can be discarded. In addition, peptide linkages like that shown in choice B also do not arises between chains. These linkages arise within peptide chains to link amino acids; but not between peptide chains to link amino acids. Therefore, choice B is incorrect as well. Finally, choice C is wrong as a 'dinitride' linkage does not occur at any level of protein structure. Again, choice D is the correct response. 15. The correct answer to question 15 is choice B. A polypeptide chain can undergo short range bending and folding to form sheets or helices. These structures arise as the peptide bonds can assume partial double bond character and so adopt different conformations. The arrangement of groups around the relatively rigid amide bond can cause R groups to alternate from side to side and hence interact with each other. In addition, the carbonyl oxygen in one region of the polypeptide chain could become hydrogen bonded to the amide hydrogen in another region of the polypeptide chain. This interaction often results in the formation of a beta-pleated sheet or an alpha helix. Localized bending and folding of a polypeptide does not constitute a proteins primary structure. The primary structure of a protein is the amino acid sequence; individual amino acids are linked to each other usually through peptide linkages. Therefore, choice A is incorrect. Choice C is incorrect since the tertiary structure of a protein is the 3D shape that arises by further folding of the polypeptide chain. Usually these non random folds are superimposed on an alpha helix and serve to give the protein a particular function. Finally, choice D is wrong since quaternary structure is the spatial arrangement between two or more associated proteins. Again, choice B is the correct response. 16. For question 16, the correct answer is choice D. The CO-NH linkage that arises between individual amino acids are known as amide linkages or more commonly, peptide linkages. This linkage forms when the carboxyl group of one amino acid reacts with the amino group of another. This process is characteristic of a condensation reaction and so results in the loss of water as well as peptide bond formation. These bonds can link an amino acid sequence to form a dipeptide, tripeptide or a polypeptide. Choice A is incorrect because this is an ester bond. Choice C is also wrong because this is an ether bond. Finally, choice B is incorrect because this bond is a hydrogen bond. While this bond may be important in determining the secondary and tertiary structures of proteins, it does not hold amino acids together in the chain. Again the correct answer is choice D. 17. The correct answer to question 17 is choice D. As I discussed earlier, peptide bonds link the primary sequence of amino acids in a protein. These bonds form between individual amino acids that can then go on to form a peptide chain. Peptide bonds are never observed when a polypeptide bends or folds to form a secondary structure. In addition, when the polypeptide folds into a three dimensional shape (which is the tertiary structure of a protein) peptide bonds do not form. Choice A is incorrect because hydrogen bonds are involved in both the secondary and tertiary structure of a protein. In the secondary structure, the polypeptide chain can fold so as to allow the carbonyl oxygen and the amine hydrogen to lie in close proximity to each other. As a result, hydrogen bonding can occur to form sheets, helices or turns. Likewise, hydrogen bonding may serve to stabilize the tertiary structure of a protein. Hydrophobic interactions can also play an important role in the tertiary structure of a protein. For example, in an aqueous environment, the hydrophobic side chains of the amino acids may interact so as to arrange themselves towards the inside of the protein. Therefore, choice B is also incorrect. Finally, choice C is wrong since interactions between charged groups (often called electrostatic interactions) can arise, especially in the tertiary structure of a protein. Again the correct answer is choice D. 18. The correct answer here is choice C. The association rule in proteins is similar to the solubility rule you learned in general chemistry. Groups of similar polarity will tend to group together and influence the secondary and tertiary structure of a protein. Choice C is correct since both groups are hydrocarbons and non polar in nature. If these were side

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Biological Molecules Test 1

chains in two different amino acids, we may expect them to interact on the interior of the protein, thus contributing to its tertiary structure. Choice A is incorrect since the first side chain is hydrophobic and the second is polar. Remember we can recognize polar groups by the presence of electronegative atoms such as oxygen and nitrogen. Anyway, this polarnon polar interaction will not occur making choice A incorrect. In choice B, the first side chain is polar whereas the second is non-polar; these two also will not interact. Choice D is the same as choice A in that the first side chain is hydrophobic and apolar whereas the second is polar. These side chains will not interact and again, choice C is the correct response.

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