Proteins and Nucleic Acids

Question 1

Relatively short chains of amino acids joined together by peptide bonds are termed:

Answer 1

peptides

Peptides are chains of amino acids that are shorter than proteins.

Question 2

The molecule EK (one glutamic acid residue bonded to one lysine residue) is a peptide. More specifically, it is a:

Answer 2

dipeptide

Dipeptides are peptides that consist of only two amino acid residues. As such, they are the shortest peptides possible.

Question 3

How many amino acid residues are present in a tetrapeptide?

Answer 3

four

For instance, the molecule CysAlaGlyLys is a tetrapeptide.

Question 4

Fill in the blanks.

Oligopeptides are molecules that contain between ________ and ________ amino acids.

Answer 4

2, 20

In other words, “oligopeptide” is a blanket term for relatively short peptides.

Question 5

While a peptide containing 17 amino acids is termed an oligopeptide, a peptide containing 64 amino acids is an example of a:

Answer 5

polypeptide

For the sake of the MCAT, you can think of polypeptides as linear peptide chains that are longer than oligopeptides (in other words, that contain more than 20 amino acid residues).

Question 6

What is the difference between a polypeptide and a protein?

Answer 6

Proteins can consist of one or more polypeptides.

In other words, a polypeptide is always defined as a single linear chain of amino acids. Some proteins are polypeptides, but other proteins are composed of multiple polypeptides attached in a more complex structure.

Question 7

True or false:

The peptide abbreviated HKA is an oligopeptide.

Answer 7

True

From the presence of three letters in HKA, we know that HKA contains three amino acid residues. Thus, HKA is both a tripeptide (a peptide containing three residues) and an oligopeptide (a peptide containing two to around 20 residues).

Question 8

Define:

primary structure

Answer 8

It refers to the linear sequence(s) of amino acids in its polypeptide chain(s).

For example, the primary structure of a protein could be written as AVYPFELK… (and so on).

Question 9

The primary structure of a protein is held together by which kind of bond?

Answer 9

Peptide bonds

amide linkages

Since primary structure refers to a linear amino acid sequence, it is held together solely by peptide bonds, which are covalent amide linkages between amino acid residues.

Question 10

Fill in the blanks.

The amino acid residues in a protein are held together by bonds between ________ and ________ atoms.

Answer 10

carbon, nitrogen

Specifically, a peptide bond connects the carbonyl carbon of one amino acid to the amino nitrogen of another. This forms an amide functional group.

Question 11

Define:

secondary structure

Answer 11

It refers to the organized, local, relatively simple folding patterns that characterize a protein.

By far the most common patterns of secondary structure that appear on the MCAT are alpha-helices and beta-pleated sheets.

Question 12

Name the two key types of secondary structure.

Answer 12

1. Alpha-helices
2. Beta-sheets (or beta-pleated sheets)

Question 13

The secondary structure of a protein is held together by which kind(s) of bond/interaction?

Answer 13

Hydrogen bonds

Secondary structure is largely rigid and predictable. In keeping with that fact, all secondary structure is held together by hydrogen bonds alone, specifically H-bonds between the carbonyl oxygen of one residue and the amino hydrogen of another.

Question 14

True or false:

Alpha helices, a form of secondary structure, largely lack proline.

Answer 14

True

Due to its unique shape, proline tends to introduce “kinks” (bends) or breaks in the rigid structure of an alpha helix. Additionally, proline’s structure renders it unable to donate the hydrogen bond needed to stabilize the helix. As a result, proline is found in alpha helices relatively rarely compared to other amino acids.

Question 15

In a beta-pleated sheet, where is proline most likely to be found?

Answer 15

edges

(or turns)

Just as it does in alpha helices, proline introduces “kinks” or bends in the structure of a beta sheet. For this reason, it is predominantly found in the areas where the sheet is supposed to be bent (that is, the turns between strands).

Question 16

Define:

tertiary structure

Answer 16

It refers to the higher-level, complex folding that produces the three-dimensional structure of a protein subunit.

Unlike secondary structure, which falls into a small number of predictable patterns, tertiary structure can vary enormously.

Question 17

The main driving force for protein folding into tertiary structure is what kind of interaction?

Answer 17

Hydrophobic interaction

Hydrophobic interactions, or the entropy-driven tendency for nonpolar parts of a protein to cluster together away from the aqueous environment, drive protein folding. (However, multiple other types of interaction have some involvement in tertiary structure.)

Question 18

Name at least three types of interactions that are involved in tertiary structure.

Answer 18

1. hydrophobic interactions
2. ionic interactions/salt bridges
3. disulfide bonds
4. hydrogen bonds

Question 19

Define:

quaternary structure

Answer 19

It refers to the interactions that hold together the subunits of a multi-subunit protein.

For instance, if the two monomers in a dimer are held together largely by ionic interactions, those interactions comprise the protein’s quaternary structure.

Question 20

True or false:

All proteins contain primary, secondary, tertiary, and quaternary structure.

Answer 20

False

While all proteins have primary, secondary, and tertiary structure, only proteins that consist of more than one subunit have quaternary structure.

Question 21

Name at least three types of interactions that are involved in quaternary structure.

Answer 21

1. hydrophobic interactions
2. ionic interactions/salt bridges
3. disulfide bonds
4. hydrogen bonds

Question 22

In its folded state, the protein hemoglobin contains which levels of protein structure?

Choose from primary, secondary, tertiary, and quaternary structure, and name all levels that apply.

Answer 22

All levels

(primary, secondary, tertiary, and quaternary structure)

All proteins in their normal folded states have primary, secondary, and tertiary structure. As a multi-subunit protein, hemoglobin also has quaternary structure. For the MCAT, you should have some familiarity with the structure of hemoglobin, which is a tetramer (four-subunit protein).

Question 23

In its folded state, the protein myoglobin contains which levels of protein structure?

Choose from primary, secondary, tertiary, and quaternary structure, and name all levels that apply.

Answer 23

Primary, secondary, and tertiary structure

In other words, myoglobin contains all levels of protein structure except quaternary structure, which only applies to multi-subunit proteins. For the MCAT, you should know that myoglobin—unlike hemoglobin—has only one subunit.

Question 24

Name all levels of protein structure to which disulfide bonds contribute.

Answer 24

Disulfide bonds are involved in tertiary and quaternary structure.

Disulfide bonds are covalent bonds between sulfur atoms of cysteine residues. Interestingly, these are the only covalent bonds (as opposed to non-covalent interactions) involved in higher-level protein folding.

Question 25

Two cysteine residues that are connected in a disulfide bond can be described using what term?

Answer 25

Cystine

Note that this word is just “cysteine” without the “e”! It refers to a cysteine dimer—in other words, two cysteine residues connected by a double bond.

Question 26

Ionic interactions contribute to which level (or levels) of protein structure?

Answer 26

Tertiary and quaternary structure

Ionic interactions, or attractions between positive and negative side chains, contribute to tertiary and quaternary structure. (You should know that, in contrast, primary structure is held together only by covalent peptide bonds, while secondary structure is held together only by hydrogen bonds.)

Question 27

An ionic interaction might involve an attraction between glutamate and which of the following amino acids?

• Aspartate
• Isoleucine
• Arginine

Answer 27

Arginine

Ionic interactions exist between positively-charged and negatively-charged side chains. Glutamate is negatively-charged, so it would be attracted to arginine’s positively-charged side chain.

(The side chain of aspartate is negative, while that of isoleucine is uncharged.)

Question 28

At physiological pH, a protein is held together largely by ionic interactions between glutamate and arginine residues. At extremely low pH (pH < 1), what would be expected to occur to these interactions?

Answer 28

They would be disrupted because glutamate would lose its negative charge.

Ionic interactions are attractive forces between positive and negative charges. At extremely low pH, glutamate’s carboxylic acid side chain is protonated and neutral, disrupting these interactions.

Question 29

Which level (or levels) of protein structure directly involves interactions between the side chains of amino acid residues?

Answer 29

Tertiary and quaternary structure

Interestingly, only tertiary and quaternary structure involve side-chain interactions! Primary structure consists of covalent bonds that form the peptide backbone, and secondary structure consists of interactions between backbone (not side-chain) atoms.

Question 30

Define:

a native protein

Answer 30

It is a protein in its normal, folded state.

For instance, native hemoglobin refers to the folded, fully functional hemoglobin protein.

Question 31

The arrangement of solvent molecules around a protein or other solute is termed the:

Answer 31

solvation layer or solvation shell

The arrangement of the solvation layer is highly dependent on entropy and plays a critical role in protein folding.

Question 32

When considering only the protein (not its surroundings), which possesses more entropy: an unfolded protein or a native (folded) protein?

Answer 32

unfolded protein

While entropy is a complex concept, for the sake of MCAT biochemistry, it can be conceptualized simply as “disorder.” An unfolded protein has much more flexibility (and thus, more disorder/randomness in its structure) than a tightly folded protein.

Question 33

All else being equal, a decrease in entropy corresponds to a [positive/negative] change in Gibbs free energy.

Choose one term from the box above to accurately complete the sentence.

Answer 33

positive

The formula for the change in Gibbs free energy is ΔG = ΔH − TΔS. Therefore, given the negative sign in this equation, a negative ΔS corresponds to a positive ΔG. The more positive the ΔG, the less spontaneous the reaction.

Question 34

Given that protein folding constitutes a decrease in the entropy of the protein, why do proteins fold spontaneously?

Answer 34

Because protein folding increases the entropy of the solvent

From the perspective of the protein alone, folding decreases entropy and therefore would be expected to be thermodynamically unfavorable. However, protein folding also increases the entropy of the solvent. If this occurs to a greater degree than the loss of entropy by the protein, then the overall process will be thermodynamically favorable.

(Note that, while both entropy and enthalpy contribute to thermodynamic favorability, enthalpy is typically not discussed in the context of protein folding.)

Question 35

Which of the following amino acids has a side chain that cannot hydrogen bond with surrounding solvent molecules?

• Methionine
• Threonine
• Lysine

Answer 35

Methionine

Methionine is a nonpolar amino acid. Nonpolar amino acids have side chains that cannot hydrogen bond with surrounding solvent molecules.

In contrast, threonine (which is polar uncharged, with an -OH-containing side chain) and lysine (which is basic and has an amino side chain) can both H-bond with the solvent.

Question 36

A protein with external-facing residues that can hydrogen bond with solvent molecules constitutes a [more/less] thermodynamically stable system than a protein with external-facing residues that cannot hydrogen bond.

Choose one term from the box above to accurately complete the sentence.

Answer 36

more

The more that a protein can hydrogen bond with surrounding solvent molecules, the less organized the solvation layer will be. Less organization corresponds to greater entropy, which constitutes a more thermodynamically stable system.

Question 37

In a folded globular protein, polar and charged residues tend to be located where?

Answer 37

On the exterior of the protein

This ensures that polar side chains, which can hydrogen bond with surrounding solvent molecules, are actually facing the solvent, while nonpolar, hydrophobic residues are not solvent-facing.

Question 38

In a folded globular protein, nonpolar residues tend to be located where?

Answer 38

Buried in the protein’s interior

This minimizes contact between nonpolar (hydrophobic) side chains and the hydrophilic solvent molecules.

Question 39

The tendency for nonpolar molecules or parts of molecules to cluster away from a polar solvent is termed:

Answer 39

the hydrophobic effect

The hydrophobic effect, which stems from entropy, is a major driving force behind protein tertiary structure.

Question 40

In a membrane-embedded protein, would asparagine or leucine be more likely to face the extracellular fluid?

Answer 40

Asparagine

In proteins, more polar residues tend to be located on the protein exterior (facing the solvent, which in this case is the extracellular fluid). Asparagine is more polar than leucine.

Question 41

On the exterior of a globular protein, a mutation replaces a serine residue with valine. How will this impact the entropy of folding of the protein?

Answer 41

The entropic penalty of protein folding will increase.

In other words, protein folding will constitute a greater decrease in entropy, meaning that folding is more unfavorable. This occurs because serine, a polar residue that “prefers” to face the exterior solvent, is being replaced with the nonpolar residue valine.

Question 42

Which part(s) of a transmembrane protein are likely to contain predominantly polar residues?

Answer 42

The extracellular and intracellular faces

A transmembrane protein contains three parts: the extracellular face, the intracellular face, and the membrane-spanning portion, which is adjacent to the nonpolar lipid bilayer. Polar residues predominate in the two solvent-facing portions.

Question 43

A large protein trimer is gradually heated until it is considered fully denatured. Which level(s) of protein structure is/are still present?

Answer 43

Primary structure only

Since the primary structure of a protein is held together by covalent bonds (specifically peptide bonds), it is much stronger than the other levels, which are held together largely by intermolecular forces. As such, full denaturation involves disrupting all levels of protein structure except primary structure.

Question 44

Most proteins that serve enzymatic functions in the human body have an optimal temperature of what value?

Answer 44

37 ºC

This is human body temperature. As one might predict, proteins in the human body tend to function best at this temperature.

Question 45

True or false:

All enzymes in the body have approximately the same optimal pH.

Answer 45

False

While all enzymes (and proteins) have an optimal pH, that value is not the same across all enzymes/proteins. For instance, parts of the digestive system are highly acidic, so enzymes that function there tend to have a relatively acidic optimal pH.

Question 46

What is the approximate optimal pH of pepsin?

Answer 46

Approximately 1.5-2.0

Pepsin is an enzyme that acts in the stomach, which is highly acidic. As such, pepsin’s optimal pH is much lower than physiological pH. Understanding that this optimal pH is somewhere in the range of 1.5 to 2 is sufficient for the MCAT.

Question 47

Which of the interactions that contribute to protein tertiary and quaternary structure are most dependent on the pH of the surroundings?

Answer 47

Ionic interactions

Ionic interactions rely on attractive forces between positively- and negatively-charged amino acid side chains. Since side chain charge varies with pH, ionic interactions are highly pH-dependent.

Question 48

What type of bonds or non-covalent interactions are disrupted by reducing agents?

Answer 48

disulfide bonds

As such, exposure to reducing agents is generally required in order to fully denature a protein’s tertiary (and sometimes quaternary) structure.

Question 49

Fill in the blanks.

From an organic chemistry perspective, reducing agents increase the number of bonds to ________ or decrease the number of bonds to _________.

Answer 49

Hydrogen, Oxygen

In the case of the reduction of disulfide bonds, reducing agents increase the number of bonds to hydrogen; as such, the disulfide bond (S-S) is broken into two separate -SH groups.

Question 50

Assuming the reaction progresses in the forward direction, does the diagram below depict reduction or oxidation?

Answer 50

Oxidation

This diagram shows the formation of a disulfide linkage, which involves the loss of bonds between sulfur and hydrogen. As such, this is oxidation. (The breakage of a disulfide linkage exemplifies reduction.)

Question 51

The reagent beta-mercaptoethanol serves to break disulfide bonds in [secondary/tertiary] structure by [reducing/oxidizing] them.

Choose one term from each box above to accurately complete the sentence.

Answer 51

tertiary, reducing

Beta-mercaptoethanol is a common reducing agent. Even if you didn’t know this, you should understand that disulfide bonds are part of tertiary (not secondary) structure and that they are broken by reduction (not oxidation).

Question 52

Compounds known as detergents disrupt which type of bonds or interactions?

Answer 52

Hydrophobic interactions

Detergents are amphipathic compounds; in other words, their molecules contain both polar and nonpolar regions. Detergents disrupt hydrophobic interactions by coating the protein in detergent molecules, which are attracted to the polar protein exterior.

Question 53

True or false:

Sodium dodecyl sulfate (SDS) is a detergent. Its sulfate head is polar, while its carbon chain (the “dodecyl” in its name) is nonpolar.

Answer 53

True

As a detergent, SDS is amphipathic, meaning that it contains a polar and a nonpolar region. The front of this card accurately characterizes its structure.

Question 54

Fill in the blanks.

The two ends of a protein are termed the ________-terminus and the ________-terminus.

Answer 54

N, C

The N-terminus is the end with a free amino group, while the C-terminus contains a free carboxylic acid group.

Question 55

In which direction are proteins conventionally written?

Answer 55

from N-terminus to C-terminus

For some reason, Clara (the author of this card) remembers this by simply recalling that it’s in reverse alphabetical order, but you could alternatively come up with a simple mnemonic for “NC” that works for you.

Question 56

The tetrapeptide PAGY, which has been investigated for its antioxidant properties, has which amino acid at its C-terminus?

Please answer with the full name of the amino acid.

Answer 56

Tyrosine

Proteins are conventionally written from N-terminus to C-terminus, meaning that the final amino acid in this tetrapeptide (Y) is the residue at the C-terminus. Y is the one-letter abbreviation for tyrosine.

Question 57

When a protein is translated from a template strand of mRNA, new amino acids are added to which end of the growing chain?

Answer 57

The C-terminus

Proteins are synthesized in the same direction in which they are written: from N-terminus to C-terminus. This means that new amino acids are progressively added to the C-terminus of the growing peptide chain.

Question 58

Peptide bonds form via a nucleophilic attack. In such a reaction, what acts as the nucleophile?

Answer 58

The nitrogen atom of the amino group

Here, organic chemistry overlaps with biochemistry! Nucleophiles are species that attack areas of relative positive charge. Thus, nucleophiles tend to possess either a negative charge or one or more lone pairs. The amino group of an attacking amino acid contains a lone pair on its nitrogen atom, which serves as the nucleophile for peptide bond formation.

Question 59

Define:

globular proteins

Answer 59

These are largely round (spherical), water-soluble, functional proteins.

These proteins often serve as enzymes or transporters in the cytoplasm or the blood.

Question 60

Define:

fibrous proteins

Answer 60

These are elongated, often hydrophobic, structural proteins.

Examples include proteins in connective tissue and the structural proteins that make up our hair, nails, and skin.

Question 61

Albumin is a water-soluble plasma protein found in the blood. Is albumin a fibrous or globular protein?

Answer 61

globular protein

As a water-soluble, functional (not structural) protein that travels through the bloodstream, albumin is a globular protein. In contrast, fibrous proteins are generally fixed in place and play structural roles.

Question 62

Keratin is a highly water-insoluble protein found in nails, hair, calluses, and skin in humans. Is keratin a fibrous or globular protein?

Answer 62

fibrous protein

As a structural protein, keratin is fibrous. Additionally, we are told that keratin is water-insoluble (hydrophobic), which is another common characteristic of fibrous proteins.

Question 63

In the sugar ribose, which carbons are attached to -OH groups?

Answer 63

The 2′ and 3′ carbons

When presented with a nucleotide’s structure on the MCAT, it can help to look at these carbons to discern whether you are being presented with RNA or DNA (as DNA lacks the 2′ -OH group).

Question 64

The sugar deoxyribose contains how many carbon atoms?

Answer 64

Five

Both deoxyribose and ribose are pentoses, meaning that they contain five carbon atoms.

Question 65

True or false:

In addition to being pentoses (five-carbon sugars), both ribose and deoxyribose typically exist as furanoses (five-membered ring structures).

Answer 65

True

It is important to be able to distinguish between the terms used to classify sugars! The terms “pentose/hexose” refer to the number of carbon atoms in a structure, while the terms “furanose/pyranose” refer to the number of atoms (of any kind) in a ring. Ribose and deoxyribose are both pentoses and furanoses.

Question 66

Sanger sequencing, a technique used for sequencing DNA, utilizes dideoxynucleotide triphosphates (ddNTPs) in its reactions. In a ddNTP, which carbon(s) is/are attached to -OH groups?

Answer 66

None

If you aren’t familiar with Sanger sequencing, you can use nomenclature to arrive at the correct answer. The word “dideoxynucleotide” indicates that these molecules are missing an -OH group in addition to what is present on a deoxynucleotide, or DNA nucleotide (which contains only a 3′ -OH group). Therefore, ddNTPs contain neither a 2′ nor a 3′ -OH.

Question 67

In the DNA backbone, the [3′/5′] carbon of the sugar of one nucleotide is connected to the [3′/5′] phosphate of the adjacent nucleotide.

Choose one term from each box above to accurately complete the sentence.

Answer 67

3′, 5′

You can answer this question by recalling that the nucleotides in DNA have phosphate groups at the 5′ carbons of their sugars (which can be remembered using the similar “f” sounds in “five-prime phosphate”).

Question 68

Name at least two atoms that are present in adenine, guanine, cytosine, uracil, and thymine.

Answer 68

1. Nitrogen
2. Carbon
3. Hydrogen

The “nitrogen” part here should be easy, as these are nitrogenous bases. Carbon and hydrogen compose much of the rest of these cyclic structures.

While most of these bases contain oxygen, it is not an answer here because it is not found in adenine.

Question 69

The fact that one DNA strand is read from its 5′ to its 3′ end while its complementary strand is read from 3′ to 5′ means that the strands of a DNA molecule can be described as:

Answer 69

antiparallel

In other words, the two strands of a molecule of double-stranded DNA are oriented in opposite directions.

Question 70

Name the three forms of DNA that can exist with regard to the structure of the double helix.

Answer 70

1. B-DNA
2. Z-DNA
3. A-DNA

These forms differ from each other with regard to the “handedness” (left or right) of the molecule and the exact distances involved, such as the distance between turns of the helix.

Question 71

Under normal physiological conditions, the most prevalent form of DNA is:

Choose from B-DNA, Z-DNA, and A-DNA.

Answer 71

B-DNA

B-DNA is far more common than either Z-DNA or A-DNA and is therefore the DNA structure that you should be most familiar with. B-DNA is a right-handed double helix that contains around 10 bases per turn of the helix and that has clear major (larger) and minor (smaller) grooves in its structure.

Question 72

At physiological pH, which of the following amino acids would be expected to be attracted to DNA?

• Lysine
• Glutamic acid
• Alanine

Answer 72

Lysine

It is very important to understand that, due to its backbone phosphate groups, DNA tends to be negatively charged. Therefore, it is attracted to positive species. Of the amino acids provided, lysine is the only one that is positive at physiological pH.

Question 73

Name the metal ion, an alkaline earth metal, that commonly acts as a cofactor for DNA-involved reactions.

Answer 73

Mg²⁺

While the overall mechanisms at play here can be complicated, you can simply think of Mg²⁺ as a highly positive ion that can stabilize the highly negative charge on DNA’s phosphate groups, which might otherwise repel certain reactants.

Question 74

Which has a lower molecular weight: guanine or uracil?

Answer 74

Uracil

Guanine is a purine (double-ring structure), while uracil is a pyrimidine (single-ring structure). Purines are significantly larger and heavier than pyrimidines.

Question 75

True or false:

The DNA backbone is held together by intramolecular forces, while complementary DNA strands are held together by intermolecular forces.

Answer 75

True

The sugar-phosphate DNA backbone is held together by covalent bonds, which exemplify intramolecular forces. Complementary strands are connected via the much weaker intermolecular force of hydrogen bonding.

Question 76

Which would require a greater temperature increase to denature: a bond between guanine and cytosine or a bond between adenine and thymine?

Answer 76

A bond between guanine and cytosine

Guanine and cytosine are held together by three hydrogen bonds, while adenine and thymine are attached by only two. This makes GC-rich DNA sequences more difficult to denature (with heat or any other denaturant).