L.1 Amino Acids & Proteins

Question 1

What are the NON-POLAR Proteinogenic Amino Acids?

Answer 1

Question 2

What are the POLAR Proteinogenic Amino Acids?

Answer 2

Question 3

What are the Charged Proteinogenic Amino Acids?

Basic and Acidic?

Answer 3

Question 4

Which two functional groups are found in all amino acids?

Answer 4

An amino acid must contain an amine and a carboxylic acid. ​Each amino acid also contains a specific side chain.

Amino acids that are tested on the MCAT are alpha amino acids, meaning that the amine group and the side chain are both bound to the carbon adjacent to the carbonyl carbon.

Question 5

What functional group is present in all peptide bonds?

Answer 5

Peptide bonds contain amides. In fact, they are sometimes alternatively known as amide linkages.

A peptide bond forms when the amine group of one amino acid attacks the carbonyl carbon of another. This is a nucleophilic substitution reaction.

Question 6

What name is given to the form of glycine pictured below?

Answer 6

This molecule is a zwitterion, meaning it is neutral overall but carries both positive and negative charge.

Amino acids often exist as zwitterions, depending on the pH of the surroundings. This is true because the carboxylic acid group is readily deprotonated, while the amine is readily protonated.

Question 7

What is the approximate pKa of an amino acid’s carboxylic acid group?

Answer 7

The carboxylic acid group has a pKa of around 2 (broadly, between 1.5 and 3).

On average, it is protonated at a pH below that value and deprotonated at a pH above it.

In a polypeptide, the carboxylic acid that does not participate in a peptide bond is known as the carboxy terminus.

Question 8

What is the approximate pKa of an amino acid’s amine group?

Answer 8

The amine group has a pKa of around 9-10.

On average, it is protonated at a pH below that value and deprotonated at a pH above it.

In a polypeptide, the amine that does not participate in a peptide bond is known as the amino terminus.

Question 9

What is the isoelectric point of an amino acid?

Answer 9

The isoelectric point, or pI, is the pH at which an amino acid is neutral overall.

When the surrounding pH is lower than the isoelectric point, the amino acid in question will have a net positive charge.

When the surrounding pH is higher, its net charge will be negative.

Question 10

Explain how to calculate the pI of an amino acid with an uncharged side chain.

Answer 10

To calculate the pI, simply average the pKas of the carboxylic acid and amino groups.

For example, the two pKas of glycine are 2.34 (carboxylic acid) and 9.60 (amine).

The pI of glycine is thus (2.34 + 9.60) / 2, or 5.97.

Question 11

Explain how to calculate the pI of an amino acid with a charged side chain.

Answer 11

For acidic amino acids, average the two most acidic pKas.

For basic amino acids, average the two most basic pKas. R

Remember, do not average all three values!

For example, the three pKas of lysine are 2.18 (carboxylic acid), 8.95 (amine), and 10.53 (side chain). Since its R group is basic, its pKa is thus (8.95 + 10.53) / 2, or 9.74

Question 12

The three pKas for arginine are 2.17, 9.04, and 12.48.

These correspond to the carboxylic acid, the amine in the backbone, and the R group, respectively.

What is arginine’s pI?

Answer 12

The pI of arginine is 10.76.

Arginine has a basic side chain, so its pI can be calculated by averaging its two most basic pKas. (9.04 + 12.48) / 2 = 10.76.

Question 13

What value can be compared to pH to determine whether a specific group on an amino acid is protonated?

Answer 13

The pKa of that group can be compared to the pH of the surroundings.

Specifically, if the pH is less (more acidic) than the pKa, that group will be protonated.

If pH is greater (more basic) than pKa, the group will be deprotonated.

Question 14

What value can be compared to pH to determine whether an entire amino acid is charged overall?

Answer 14

The isoelectric point, or pI, of the amino acid can be compared to the pH of the surroundings.

Specifically, if pH is less than the pI, the amino acid will be positively charged. If pH is greater than the pI, the group will be negative.

Question 15

Which of the standard amino acids, if any, are chiral?

Answer 15

All standard amino acids are chiral except for glycine.

Nearly all of the amino acids seen on the MCAT have at least one chiral center, the alpha carbon. Glycine is the one exception: its R group is simply a hydrogen atom, so its alpha carbon is not bound to four different groups.

Question 16

What is the relationship between D-leucine and L-leucine?

Answer 16

These two amino acids are enantiomers.

All amino acids except glycine can be found as either D or L stereoisomers.

Note that only L amino acids are found in proteins.

Human (and other) enzymes are stereospecific and react with the L isomer alone.

Question 17

What word describes the interactions between polar amino acids and water?

Answer 17

Amino acids with polar side chains tend to be hydrophilic. This means that they interact well with water and, in some cases, can hydrogen bond.

On the MCAT, hydrophilicity/hydrophobicity is often tested as a comparison. You should be able to look at two structures and discern which is more polar than the other.

Question 18

What word describes the interactions between nonpolar amino acids and water?

Answer 18

Amino acids with nonpolar side chains tend to be hydrophobic. This means that they interact poorly with water and generally cluster with other nonpolar groups.

On the MCAT, hydrophilicity/hydrophobicity is often tested as a comparison. You should be able to look at two structures and discern which is more polar than the other.

Note that another term for “hydrophobic” is “lipophilic.”

Question 19

What names are given to the deprotonated forms of glutamic acid and aspartic acid, respectively?

Answer 19

The deprotonated form of glutamic acid is known as glutamate, while the deprotonated form of aspartic acid is aspartate.

It can help to remember that in general, deprotonated carboxylic acids are called “carboxylates.”

Question 20

Which amino acids contain at least one sulfur atom?

Answer 20

The sulfur-containing amino acids are cysteine and methionine.

Note that cysteine, but not methionine, can form disulfide bridges. When two cysteine molecules connect with a disulfide linkage, the resulting structure is known as cystine.

Question 21

Which amino acid tends to produce turns or “kinks” in a protein’s secondary structure?

Answer 21

Proline produces kinks in secondary structures such as alpha helices and turns in beta sheets.

This occurs because proline, unlike any other common amino acid, has an R group that is bound directly to its amino terminal in a cyclic structure.

Question 22

For aspartic acid, the pKas of the carboxy-terminal, side chain, and amino-terminal are 2.10, 3.86, and 9.82, respectively.

Which of those groups will be protonated at a pH of 5?

Answer 22

Only the amino terminal will be protonated.

A group will be protonated at a pH lower than its pKa, and deprotonated at a higher pH. Only the amino terminal (pKa 9.82) is in a relatively more acidic solution.

Question 23

Which amino acids contain aromatic rings?

Answer 23

Phenylalanine, tyrosine, and tryptophan all contain aromatic side chains. Note that while histidine is classified as a basic amino acid, its structure also includes an aromatic ring.

Remember that phenylalanine is simply “phenyl” (a benzene ring) plus “alanine.” Tyrosine’s side chain involves a phenol group, while tryptophan contains a two-ring system called an indole.

Question 24

For lysine, the pKas of the carboxy-terminal, side chain, and amino-terminal are 2.18, 10.53, and 8.95, respectively.

Which of those groups will be charged at physiological pH?

Answer 24

All three groups will be charged. The carboxy terminal will be deprotonated (negative), while the other two groups will be protonated (positive).

Be careful to discern whether a question asks about the charge or protonation state of a group. Acidic groups are only charged when deprotonated, while basic groups are charged when protonated.

Question 25

What will be the net charge on alanine at a pH of 1.2?

Answer 25

The net charge on alanine will be +1.

Since the pH is so extremely acidic here, we do not need to know the exact pKas of alanine’s two groups. The pKa of the carboxy-terminal is around 2, so it will be protonated (making it a neutral COOH). The pKa of the amine is around 9-10, so it will also be protonated (making it NH3+).

Question 26

What will be the net charge on alanine at physiological pH?

Answer 26

The net charge on alanine will be zero. In other words, it will be a zwitterion and neutral overall.

Physiological pH is approximately 7.4. This is above the pKa of the carboxy-terminal (leading it to be deprotonated, or COO-) but below that of the amino-terminal (leading it to be protonated, or NH3+).

Question 27

What separation technique is used to isolate amino acids based on their isoelectric points?

Answer 27

Isoelectric focusing is used to separate amino acids by pI.

This process involves an anode, or positive terminal, and a cathode, or negative terminal. Any amino acid with a net charge will migrate toward one terminal until it reaches the region with the same pH as its own isoelectric point.

Question 28

In isoelectric focusing, what charge is given to the anode?

Answer 28

The anode is positively charged.

Isoelectric focusing, or gel electrophoresis in general, resembles an electrolytic cell. As in any cell, electrons move from anode to cathode. However, electrolytic cells are nonspontaneous, meaning that they require outside power input. Such energy input is necessary because electrons are being forced off of a positive terminal (the anode) and onto a negative one (the cathode).

Question 29

During isoelectric focusing, an amino acid migrates toward the anode until it stops at a region of pH 2.7.

What is the pI of this amino acid?

Answer 29

This amino acid must have a pI of 2.7.

Isoelectric focusing is a technique that separates amino acids by their isoelectric points. An AA will migrate until it reaches a section of the gel with a pH equal to its pI.

Question 30

During isoelectric focusing, an amino acid migrates toward the anode until it stops at a region of pH 2.7.

What was its net charge during the migration?

and at the end of the experiment, respectively?

Answer 30

While the AA was migrating, its net charge was negative. It comes to a stop when that charge becomes neutral.

In isoelectric focusing, the anode is positive. Amino acids that migrate toward it, then, must be negative. These AAs stop moving when the surrounding pH is equal to their pI values, at which point they exist as neutral zwitterions.

Question 31

Which is least likely to rotate plane-polarized light?

Answer 31

Glycine is least likely to display such optical activity, since it is achiral. Its alpha carbon is bound to two hydrogen atoms.

All other amino acids that appear on the MCAT contain at least one chiral center.

Question 32

Describe is the structure of an amino acid?

3 Main Focus Points

Answer 32

Amino Group, Carboxylic Acid Group, Hydrogen, R Groups

1. Chiral (Except for Glycine)

2. All L-Amino Acids that Function in Body

3. S-Absolute Configuration (Except for Cystein R)

Question 33

What is an AMPHOTERIC molecule?

How do ionizable groups act under basic and acidic conditions?

What does the pKa of a group mean?

Answer 33

A molecule that can Accept or Donate Protons depending on its environment

1. Ionizable Groups; Gain H under Acidic Conditions

Lose H under Basic Conditions

2. pKa of a group = pH at wich 1/2 and 1/2 of protonated and deprotonated molecules exist in solution

Question 34

How does the region of a pKa and pI of an amino acid on a titration curve look like?

Answer 34

pKa = FLAT

pI = Vertical (buffer region)