Chapter 1: Amino Acids, Peptides, and Proteins (Kaplan)

Question 1

Remarkably, the difference between the normal form of hemoglobin (HbA) and the one that causes sickle cell disease (HbS), is a seemingly minor one. All it takes is a change in a single amino acid on the surface of hemoglobin: the ___ amino acid in 2 of its 4 chains is changed from ________ acid to ______. That minor difference allows the deoxygenated form of HbS to aggregate and precipitate, which leads to the sickled shape – and all the symptoms – of sickle cell disease.

Answer 1

6th glutamic acid to valine p. 3

Question 2

Amino acids are molecules that contain two functional groups: an amino group (____) and a carboxyl group (_____).

Answer 2

• NH₂
• COOH

Question 3

The alpha-amino acids are the group in which the amino group and the carboxyl group are bonded to the same carbon, the _____-______ of the carboxylic acid. This means the carbon that is ________ to the carboxyl carbon.

Answer 3

alpha-carbon

adjacent

p. 4

Question 4

Amino acids DO/ DO NOT need to have both the amino and carboxyl groups bonded to the same carbon.

Answer 4

do NOT

Question 5

Name an example of an amino acid in the body which is not specified by a codon in the genetic code or incorporated into proteins.

Answer 5

ornithine, one of the intermediates in the urea cycle, which is the metabolic process by which the body excretes excess nitrogen

p. 4

Question 6

The AAMC has specifically stated they’ll focus on the 20 alpha-amino acids encoded by the human genetic code, also called ____________ amino acids.

Answer 6

proteinogenic

Question 7

What does chiral/ achiral mean?

Answer 7

Chiral means it’s asymmetric in such a way that the structure and its mirror image are not superimposable.

Achiral means that the object IS superimposable on its mirror image.

The term chiral comes from the Greek word for hand.

Question 8

All chiral amino acids used in eukaryotes are _-amino acids.

Answer 8

L-amino acids

Question 9

Name the 7 amino acids that fall into the category of nonpolar, nonaromatic side chains.

Answer 9

GAVLIMP

glycine

alanine

valine

leucine

isoleucine

methionine

proline

p. 6

Question 10

Name the 3 amino acids that have uncharged aromatic side chains.

Answer 10

tryptophan, phenylalanine, tyrosine

(TPT)

p. 6

Question 11

Which amino acid is achiral and also the smallest amino acid?

Answer 11

glycine

p. 5

Question 12

Proline is unique in that it forms a ______ amino acid. In all the other amino acids, the amino group is attached ____ to the alpha-carbon. In proline, however, the amino nitrogen becomes a part of the side chain, forming a 5-membered ring. That ring places notable constraints on the flexibility of proline, which limits where it can appear in a protein and can have significant effects on the proline’s role in secondary structure.

Answer 12

cyclic

only

p. 6

Question 13

Except for _______, all amino acids are chiral – and except for ________, all of them have an (S) absolute configuration.

Answer 13

glycine

cysteine

Question 14

An imine is specifically a molecule with a…

Some textbooks problematically describe proline as an imino acid bc the amino nitrogen forms 2 bonds to carbon.

Answer 14

…carbon-nitrogen double bond.

p. 6

Question 15

Phenylalanine has a benzyl side chain. What does that mean?

Answer 15

Benzyl means a benzene ring plus a -CH₂ group.

p. 6

Question 16

5 amino acids have side chains that are polar but not aromatic. Name them.

Which is the 1 polar amino acid that is aromatic and has a neutral charge?

Answer 16

(Mnemonic: SAG-C-2T)

Serine, Asparagine, Glutamine, Cysteine, Threonine

Tyrosine is aromatic and neutral.

(Remember also that tyrosine is aromatic, but asparagus is not, which is how you can remember that asparagine is the A in the mnemonic, since there are 3 other amino acids that start with A.)

p. 7

Question 17

Asparagine and glutamine have amide side chains. What is unique amount these amino acids?

Answer 17

Unlike the amino group common to all amino acids, the amide nitrogens do not gain or lose protons with changes in pH; they do not become charged.

p. 7

Question 18

Cysteine contains a thiol (-SH) group in its side chain. Why is the S-H bond weaker than the O-H bond?

What is the significance of this?

Answer 18

because sulfur is larger and less electronegative than oxygen

It leaves the thiol group in cysteine prone to oxidation.

p. 7

Question 19

Only 2 of the 20 amino acids have negative charges on their side chains at physiological pH (7.4). What are they?

Answer 19

aspartic acid and glutamic acid

p. 8

Question 20

Note that ________ is simply the deprotonated form of aspartic acid, and _________ is the deprotonated form of glutamic acid.

Answer 20

aspartate

glutamate

*on the MCAT you are likely to see these anion names instead of acid names because most acids in cells exist in the deprotonated form.

p. 8

Question 21

Strongly hydrophobic amino acids tend to be found in the ________ of proteins.

Answer 21

interior

p. 9

Question 22

The amino acids with long _____ side chains – alanine, isoleucine, leucine, valine, and phenylalanine – are all strongly hydrophobic, and thus more likely to be found in the interior of proteins.

Answer 22

alkyl

p. 9

Question 23

All the amino acids with charged side chains – __________ charged histidine, arginine, and lysine, plus __________ charged glutamate and aspartate – are hydrophilic, as are the amides asparagine and glutamine. The remaining amino acids lie somewhere in the middle and are neither particularly hydrophilic nor particularly hydrophobic.

Answer 23

POSITIVELY

NEGATIVELY

p. 9

Question 24

The histidine residue in chymotrypsin’s ______ ____ removes a proton from the -COOH group in an aspartic acid residue, which can then deprotonate a serine residue.

Answer 24

active site

p. 8

Question 25

What is the aromatic ring in histidine with 2 nitrogen atoms called?

Answer 25

an imidazole

p. 8

Question 26

What does the notation “E6V” mean in turns of a mutation by substitution?

Answer 26

That the sixth amino acid, glutamic acid (E), has been changed to valine (V).

p. 10

Question 27

Because amino acids have both an acidic carboxylic acid group and a basic amino group, this makes them an __________ species.

Answer 27

amphoteric

p. 12

Question 28

The pK_a of a group is the pH at which, on average, half of the molecules of that species are deprotonated.

If the pH is LESS than the pK_a, a majority of the species will be ________. If the pH is HIGHER than the pK_a, a majority of the species will be ________.

Answer 28

protonated

deprotonated

p. 12

Question 29

Because all amino acids have at least 2 groups that can be deprotonated, they all have at least 2 pK_a values. The first one, pK_a1, is the pK_a for the _____ group, and usually around _. For most amino acids, the second pK_a value, pK_a2, is the pK_a for the amino group, and is usually around _ or _.

If the amino acid has an ionizable side chain, there will be more than 2 pK_a values.

Answer 29

carboxyl, 2

9 or 10

p. 12

Question 30

At very acidic pH values (such as that of the environment of the stomach), amino acids tend to be ________ charged.

Answer 30

positively

p. 12

Question 31

At physiological pH, you will not find amino acids with the carboxylate group protonated (-COOH), AND the amino group unprotonated (-NH₂). In what form will be find these groups?

Answer 31

The carboxyl group will be deprotonated (-COO^-) and the amino group will be protonated (in its conjugate acid form: -NH₃⁺)

Question 32

At very alkaline pH values, amino acids tend to be…

Answer 32

…negatively charged.

p. 13

Question 33

The isoelectric point is the pH at which the molecule is electrically _______.

Answer 33

neutral

p. 15

Question 34

The pI is calculated as the average of the 2 nearest pKa values. For amino acids with non-ionizable side chains, the pI is usually around _.

Answer 34

6

Question 35

Because glutamic acid has two carboxyl groups and one amino group, its charge in its fully protonated state is still __.

Answer 35

+1

Question 36

the pI of an acidic amino acid = [pK_{a,R group} + pK_{a,COOH group}] / 2

What is the pI of a basic amino acid?

Answer 36

pI = [pK_{a,R group} + pK_{a,NH3+ group}] / 2

Question 37

We think of peptide bond formation as a condensation or dehydration reaction, but it can also be viewed as an ____ substitution reaction, which can occur with all carboxylic acid derivatives.

Answer 37

acyl

p. 17

Question 38

When a peptide bond forms, the __________ carbonyl carbon on the first amino acid is attacked by the __________ amino group on the second amino acid. The hydroxyl group of the carboxylic acid is then kicked off, and the result is the formation of a peptide (amide) bond.

Answer 38

electrophilic

nucleophilic

p. 17

Question 39

Do amide groups exhibit resonance? And why?

Answer 39

Yes, because they have delocalizable pi electrons in the carbonyl and in the lone pair on the amino nitrogen, thus the C-N bond in the amide has partial double bond character.

p. 18

Question 40

Why do we draw peptide bonds in a certain order, from NH₃ on the left to COOH group on the right?

Answer 40

They are drawn in the same order that they are synthesized by ribosomes!

p. 18

Question 41

Because of the double bond character, rotation of the protein backbone around the C-N amide bonds is ________, which makes the protein rigid, however the rest of the bonds are sigma with free rotation.

Answer 41

restricted

p. 18

Question 42

What is an oligopeptide?

Answer 42

a string of 2 or more amino acids, up to 20 amino acids

2 amino acids may be called a dipeptide, and 3 may be called a tripeptide

p. 19, 33

Question 43

True or false, in organic chemistry, amides can be hydrolyzed using acid or base catalysis.

Answer 43

True

p. 18

Question 44

The primary structure alone encodes all the information needed for folding at all of the higher structural levels; the secondary, tertiary, and quaternary structures a protein adopts are the most _______ _______ arrangements of the primary structure in a given environment.

Answer 44

energetically favorable

p. 20

Question 45

Which amino acid forms a kink in a peptide chain, and thus is rarely found in the middle of beta pleated sheets, but often found in the turns between the chains of a beta pleated sheet or at the start of an alpha helix?

Answer 45

proline

p. 21

Question 46

in an alpha helix, the helix is stabilized by intermolecular hydrogen bonds between a carbonyl oxygen atom and an amide hydrogen atom 4 residues down the chain. This means the side chains of the amino acids point ____ from the helix core.

Answer 46

away

p. 20

Question 47

Conjugated proteins derive part of their function from covalently attached molecules called _________ groups. These groups can be organic molecules, vitamins, metal ions, lipids, carbohydrates, or nucleic acids.

Answer 47

prosthetic

E.g. lipoproteins, glycoproteins, nucleoproteins

p. 25

Question 48

Hemoglobin is an example of a conjugated protein. Each of its subunits contains a prosthetic group. What is this prosthetic group called?

Answer 48

heme

p. 25

Question 49

What is tertiary structure?

What are the subtypes of tertiary structure?

Answer 49

The 3-D shape of a protein.

hydrophobic interactions, acid-base/ salt bridges, disulfide links

p. 34

Question 50

What bonds stabilize the tertiary structure of a protein?

(Note: quaternary structure is stabilized by these same forces.)

Answer 50

van der Waals forces, hydrogen bonds, ionic bonds, and covalent bonds

p. 34

Question 51

What is quaternary structure of a protein?

Answer 51

the interactions between separate subunits of a multisubunit protein.

p. 34

Question 52

What is the primary motivation for hydrophobic residues in a polypeptide to move to the interior of the protein?

Answer 52

Moving hydrophobic residues to the interior of a protein increases entropy by allowing water molecules on the surface of the protein to have more possible positions and configurations. This positive ΔS makes ΔG < 0, stabilizing the protein.

p. 34

Question 53

If a protein loses its ________ structure, a process called denaturation, it loses its function.

Answer 53

tertiary

p. 23

Question 54

The 2 main causes of denaturation are…

Answer 54

….heat and solutes.

Heat is energy which, if high enough, can overcome the hydrophobic interactions that hold a protein together, causing it to unfold.

p. 28

Question 55

What is an example of a solute that can denature proteins by directly interfering with the forces that hold the protein together.

Answer 55

urea

p. 29

Question 56

D-amino acids can exist in __________.

Answer 56

prokaryotes

p. 30

Question 57

Amino acids can be titrated; the titration curve is nearly _______ at the pK_a values of the amino acid, and nearly _______ at the pI of the amino acid.

Answer 57

flat

vertical

p. 30

Question 58

Breaking a peptide bond is a _________ reaction.

Answer 58

hydrolysis

p. 31

Question 59

α-helices are _________ coils around a central axis.

Answer 59

clockwise

p. 31

Question 60

Why is cysteine the only amino acid with an S absolute configuration?

Answer 60

Because it is the only one that has an R group that has a higher priority than a carboxylic acid according to Cahn-Ingold-Prelog rules.

p. 33

Question 61

Glutamic acid and aspartic acid are acidic amino acids bc they have an extra ________ group. At neutral pH, both of these groups are deprotonated and thus negatively charged.

Answer 61

carboxyl

p. 38

Question 62

What type of structure may or may not be disrupted by denaturation?

Answer 62

secondary structure

p. 38

Question 63

Which 2 amino acids also have a chiral carbon in their side chain?

Answer 63

threonine and isoleucine

p. 39

Question 64

Which amino acid is most likely to be found in the highest concentration in the triple helix structure of collagen?

Answer 64

glycine, bc it has the smallest side chain of all, and steric hindrance is the biggest potential problem with the other larger amino acids.

p. 39