MCAT AAMC OUTLINE EXAM
QUESTIONS AND ANSWERS GRADED A+
2025/2026
Content Category 1A: Structure and function of proteins and their constituent amino acids
1A.1) amino acids
* description
- Amino acids contain two functional groups, an amino group (-NH2) and a carboxyl group (-
COOH)
- Alpha amino acids are those where both functional groups are attached to the same carbon.
- Side chain/R group and hydrogen atom are also attached to alpha carbon.
- Side chain determines the properties of amino acids and its functions.
Absolute configuration at the α position
* Alpha carbon is usually a chiral center since it has four different groups attached to it.
- Thus most amino acids are optically active
- Glycine is the only exception since it has a hydrogen as its R group.
* All chiral amino acids are L-amino acids, which means that the amino group is drawn on
the left side for the Fischer projection.
- Translates to an (S) absolute configuration for almost all chiral amino acids.
- Cysteine is the only amino acid that has an L-amino acid configuration but has an (R) absolute
configuration. This is because the carboxyl group is not the highest priority functional group.
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,hydrophobic and hydrophilic amino acids
* Amino acids with long alkyl side chains - alanine, isoleucine, leucine, valine, and phenylalanine
- are strongly hydrophobic, and are thus more likely to be found in the interior of proteins
* All amino acids with charged side chains - histidine, arginine, lysine, glutamate, and aspartate -
are hydrophilic
- So are the amides asparagine and glutamine
* Remaining amino acids are somewhere in the middle between being philic and phobic.
Acid Base Chemistry of Amino Acids
* Amino acids are an amphoteric species since they have an acidic carboxyl group and a basic
amino group.
* Ionizable groups tend to gain protons under acidic conditions and lose them under basic
conditions.
- i.e. at low pH an ionizable group will be protonated
* The pKa of a group is the pH at which half of the molecules of the species are deprotonated or
[HA]=[A-]
- If pH is lower than pKa then the majority of the species will be protonated.
protonation and deprotonation
* All amino acids have at least two pKa values.
- pKa1 is the pKa of the carboxyl group and is usually around 2
- pKa2 is the pKa of the amino group and is usually around 9-10
* If the amino acid has an ionizable side chain, then there will be three pKa values.
positively charged under acidic conditions
- At pH below 1, the pKa is far below that of the amino group, so the amino group is fully
protonated (-NH3+)
- Additionally, the carboxylic acid group is fully protonated (-COOH)
- At very acidic pH values, amino acids tend to be positively charged.
zwitterions at intermediate pH
At pH of 7.4, carboxylic acid pKa has been moved past. As such, you will not find amino acids
with their carboxylate group protonated and the amino group unprotonated
- Amine group stays protonated since the pKa still is not high enough.
2 @COPYRIGHT 2025/2026 ALLRIGHTS RESERVED.
,- Resulting molecule has both a positive charge and a negative charge, but is overall
neutral.
- These are called dipolar ions or zwitterions. These exist in water as internal salts.
negatively charged under basic conditions
- pKa of the amino group is below the pKa at higher pH's>10, which means that the amino group
deprotonates to NH2
- So the molecules become negatively charged at high pH
titration of amino acids
- The titration curve should look like a combination of two monoprotic acid curves or three
curves if the side chain is charged.
- Starting at low pH, the amino acid is fully protonated. As the pH approaches pKa1, the solution
begins acting like a buffer and this is characterized by a straight line on the graph.
- When pH= pKa1, then [HA]=[A-]
- Isoelectric Point (pI): the pH at which the molecule is electrically neutral which means that the
amino acid exists exclusively in its zwitterion form2.
- Can be calculated for neutral amino acids by the following: (pka1 + pka2)/2
- Pass through a secondary buffer phase as more base is added since the amino group begins to
deprotonate.
amino acids with charged side chains
- Amino acids with charged side chains - like glutamic acid and lysine - the titration curve has an
extra step, but follows the same principles.
- For an amino acid such as glutamic acid, the two carboxyl groups mean that the deprotonated
form will still have a charge of +1.
- The first proton will be deprotonated form the carboxyl groups, while the second proton will
instead be protonated from the carboxyl side group.
* Lysine has two amino groups and one carboxyl group, so its charge is +2 in its fully protonated
state.
- First proton is lost from carboxyl group as usual, but second proton to make the molecule
neutral is not lost until a pKa of around 9.
acidic amino acids
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, - aspartic acid
- glutamic acid
basic amino acids
- lysine
- arginine
- histidine
* Reaction
- sulfur linkage for cysteine and cystine
- peptide linkage
- hydrolysis
sulfur linkage for cysteine and cystine
- Cysteine = amino acid with the thiol R group
- Cystine = 2 cysteines that have formed a disulfide bond
peptide linkage
*polypeptides and proteins
- dehydration reaction (removal of water)
- peptide bond has slight double bond character - prevents bond from rotating freely, affects
secondary structure and tertiary structure to some extent
- Residues are joined together through peptide bonds which is a specialized form of an amide
bond that forms between the –COO- group of one amino acid and the NH3+ group of another
amino acid.
hydrolysis
- process of breaking peptide bonds
- most macromolecules of living cells are broken apart by hydrolysis
ex): ATP hydrolysis, digestion
1A2) Protein Structure
proteins
- are polypeptides made from amino acids and vary in length
4 @COPYRIGHT 2025/2026 ALLRIGHTS RESERVED.
QUESTIONS AND ANSWERS GRADED A+
2025/2026
Content Category 1A: Structure and function of proteins and their constituent amino acids
1A.1) amino acids
* description
- Amino acids contain two functional groups, an amino group (-NH2) and a carboxyl group (-
COOH)
- Alpha amino acids are those where both functional groups are attached to the same carbon.
- Side chain/R group and hydrogen atom are also attached to alpha carbon.
- Side chain determines the properties of amino acids and its functions.
Absolute configuration at the α position
* Alpha carbon is usually a chiral center since it has four different groups attached to it.
- Thus most amino acids are optically active
- Glycine is the only exception since it has a hydrogen as its R group.
* All chiral amino acids are L-amino acids, which means that the amino group is drawn on
the left side for the Fischer projection.
- Translates to an (S) absolute configuration for almost all chiral amino acids.
- Cysteine is the only amino acid that has an L-amino acid configuration but has an (R) absolute
configuration. This is because the carboxyl group is not the highest priority functional group.
1 @COPYRIGHT 2025/2026 ALLRIGHTS RESERVED.
,hydrophobic and hydrophilic amino acids
* Amino acids with long alkyl side chains - alanine, isoleucine, leucine, valine, and phenylalanine
- are strongly hydrophobic, and are thus more likely to be found in the interior of proteins
* All amino acids with charged side chains - histidine, arginine, lysine, glutamate, and aspartate -
are hydrophilic
- So are the amides asparagine and glutamine
* Remaining amino acids are somewhere in the middle between being philic and phobic.
Acid Base Chemistry of Amino Acids
* Amino acids are an amphoteric species since they have an acidic carboxyl group and a basic
amino group.
* Ionizable groups tend to gain protons under acidic conditions and lose them under basic
conditions.
- i.e. at low pH an ionizable group will be protonated
* The pKa of a group is the pH at which half of the molecules of the species are deprotonated or
[HA]=[A-]
- If pH is lower than pKa then the majority of the species will be protonated.
protonation and deprotonation
* All amino acids have at least two pKa values.
- pKa1 is the pKa of the carboxyl group and is usually around 2
- pKa2 is the pKa of the amino group and is usually around 9-10
* If the amino acid has an ionizable side chain, then there will be three pKa values.
positively charged under acidic conditions
- At pH below 1, the pKa is far below that of the amino group, so the amino group is fully
protonated (-NH3+)
- Additionally, the carboxylic acid group is fully protonated (-COOH)
- At very acidic pH values, amino acids tend to be positively charged.
zwitterions at intermediate pH
At pH of 7.4, carboxylic acid pKa has been moved past. As such, you will not find amino acids
with their carboxylate group protonated and the amino group unprotonated
- Amine group stays protonated since the pKa still is not high enough.
2 @COPYRIGHT 2025/2026 ALLRIGHTS RESERVED.
,- Resulting molecule has both a positive charge and a negative charge, but is overall
neutral.
- These are called dipolar ions or zwitterions. These exist in water as internal salts.
negatively charged under basic conditions
- pKa of the amino group is below the pKa at higher pH's>10, which means that the amino group
deprotonates to NH2
- So the molecules become negatively charged at high pH
titration of amino acids
- The titration curve should look like a combination of two monoprotic acid curves or three
curves if the side chain is charged.
- Starting at low pH, the amino acid is fully protonated. As the pH approaches pKa1, the solution
begins acting like a buffer and this is characterized by a straight line on the graph.
- When pH= pKa1, then [HA]=[A-]
- Isoelectric Point (pI): the pH at which the molecule is electrically neutral which means that the
amino acid exists exclusively in its zwitterion form2.
- Can be calculated for neutral amino acids by the following: (pka1 + pka2)/2
- Pass through a secondary buffer phase as more base is added since the amino group begins to
deprotonate.
amino acids with charged side chains
- Amino acids with charged side chains - like glutamic acid and lysine - the titration curve has an
extra step, but follows the same principles.
- For an amino acid such as glutamic acid, the two carboxyl groups mean that the deprotonated
form will still have a charge of +1.
- The first proton will be deprotonated form the carboxyl groups, while the second proton will
instead be protonated from the carboxyl side group.
* Lysine has two amino groups and one carboxyl group, so its charge is +2 in its fully protonated
state.
- First proton is lost from carboxyl group as usual, but second proton to make the molecule
neutral is not lost until a pKa of around 9.
acidic amino acids
3 @COPYRIGHT 2025/2026 ALLRIGHTS RESERVED.
, - aspartic acid
- glutamic acid
basic amino acids
- lysine
- arginine
- histidine
* Reaction
- sulfur linkage for cysteine and cystine
- peptide linkage
- hydrolysis
sulfur linkage for cysteine and cystine
- Cysteine = amino acid with the thiol R group
- Cystine = 2 cysteines that have formed a disulfide bond
peptide linkage
*polypeptides and proteins
- dehydration reaction (removal of water)
- peptide bond has slight double bond character - prevents bond from rotating freely, affects
secondary structure and tertiary structure to some extent
- Residues are joined together through peptide bonds which is a specialized form of an amide
bond that forms between the –COO- group of one amino acid and the NH3+ group of another
amino acid.
hydrolysis
- process of breaking peptide bonds
- most macromolecules of living cells are broken apart by hydrolysis
ex): ATP hydrolysis, digestion
1A2) Protein Structure
proteins
- are polypeptides made from amino acids and vary in length
4 @COPYRIGHT 2025/2026 ALLRIGHTS RESERVED.
