3.1 Proteins Are Built from a Repertoire of 20 Amino Acids
Learning goal: Distinguish between the Fischer projection and stereochemical rendering of molecules.
Answer: A Fischer projection is used when it's more important to visualize the constituent atoms (like carbons,
hydrogens, and other atoms) in a molecule rather than its shape.
The projection represents bonds around a central carbon atom using horizontal and vertical lines:
• Horizontal bonds project out of the page toward the viewer.
• Vertical bonds project behind the page, away from the viewer.
Every atom is explicitly identified, making it easier to understand the connectivity and arrangement of atoms in the molecule.
Stereochemical rendering focuses on the shape of the molecule, which is crucial for understanding its function.
These diagrams simplify the depiction by:
• Not explicitly showing all carbon and hydrogen atoms (unless they are functionally important).
• Highlighting functional groups, which are key to the molecule’s activity.
Bonds are shown using a combination of:
• Solid wedges: Bonds coming out of the page toward the viewer.
• Dashed wedges: Bonds going into the page away from the viewer.
• Straight lines: Bonds lying in the plane of the page.
Key Differences:
Aspect Fischer Projection Stereochemical Rendering
Purpose Visualizing constituent atoms and connectivity. Understanding the shape and function.
Detail Explicitly shows all atoms (e.g., carbons, hydrogens). Omits some atoms for simplicity (focus on function).
Bond Representation Horizontal/vertical lines for bonds. Wedges and straight lines to depict 3D structure.
Emphasis Atomic structure and arrangement. Molecular shape and activity.
Learning goal: Understand the chirality of amino acids.
Answer: Amino acids are chiral molecules because their central carbon atom (the α-carbon) is bonded to four different groups:
• An amino group (-NH2 or NH3⁺),
• A carboxylic acid group (-COOH or COO⁻),
• A hydrogen atom (H),
• A side chain (R group).
This arrangement makes them tetrahedral and capable of existing as two mirror-image isomers: L isomer and D isomer.
Learning goal: Know that proteins only contain L amino acids.
Answer: Although both L and D forms of amino acids are theoretically possible, only L amino acids
are used in the synthesis of proteins in biological systems. However, the reason for this preference
remains unclear. A possible explanation is that L amino acids have a slightly higher solubility than
their racemic DL mixtures, which could have been amplified over time in evolutionary processes
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,Learning goal: Draw the structure of an amino acid and indicate the following features that are common to all amino acids: functional groups,
side chains, and ionic forms.
Answer: An α-amino acid has the following structure:
1. Functional groups:
• Amino group (-NH3⁺ at physiological pH).
• Carboxyl group (-COO⁻ at physiological pH).
2. Side chain (R group):
• This is the variable group that differs among the 20 amino acids and determines their unique properties.
3. Ionic forms:
• At neutral pH (~7), amino acids exist as zwitterions (dipolar ions):
o The amino group is protonated (NH3⁺).
o The carboxyl group is deprotonated (COO⁻).
• At low pH, both groups are protonated:
o NH3⁺ and -COOH.
• At high pH, both groups lose their protons:
o NH2 and COO⁻.
Question 1: Here is the amino acid Leucine displayed. Is the amino acid shown D or L? Is naturally occurring Leucine D or L?
Answer: The amino acid shown is L and naturally occurring Leucine is also L. All amino acids in proteins are L isomers.
Question 2: Some molecules contain both positive and negative charges but overall have a neutral charge, like leucine. What
are these molecules called?
a. Enantiomers
b. Amino acid
c. Racemate
d. Zwitterion
e. Amphipath
Answer: Zwitterion.
Question 3: Valine is an amino acid that can exist as a zwitterion. What is the charge of valine at the following pH
values? pH-values: pH = 0, pH = 6 and pH = 14.
Answer: The amino group and the carboxyl group can give charge to the amino acid. Think if they are protonated or
not at the given pH. pH = 0 → +1; pH = 6 → 0; pH = 14 → -1.
3.2 Amino Acids Contain a Wide Array of Functional Groups
Learning goal: Classify each of the 20 amino acids according to the side chain on the α-carbon as aliphatic, aromatic, sulfur-containing, aliphatic
hydroxyl, basic, acidic, or amide derivative.
Answer:
Hydrophobic Amino Acids (Nonpolar R Groups):
• Aliphatic Side Chains: Hydrocarbon chains that are nonpolar and hydrophobic.
• Properties: Hydrophobic; tend to cluster together in the interior of proteins (hydrophobic effect).
o Glycine (Gly, G): Simplest amino acid; R group is a hydrogen atom. Unique: Achiral.
o Alanine (Ala, A): Contains a methyl group (-CH3).
o Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I): Branched hydrocarbon side chains.
o Methionine (Met, M): Contains a thioether group (-S-) in a largely aliphatic chain.
o Proline (Pro, P): Has a cyclic structure where the side chain is bonded to both the α-carbon and the amino nitrogen, creating
conformational restrictions.
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,Hydrophobic Amino Acids (Nonpolar R Groups):
• Aromatic Side Chains: Contain ring structures with delocalized π-electrons.
• Properties: Hydrophobic; tend to cluster together in the interior of proteins (hydrophobic effect).
o Phenylalanine (Phe, F): Contains a phenyl group attached to an aliphatic chain.
o Tryptophan (Trp, W): Contains an indole group (two fused rings, one with NH).
Polar Amino Acids (Neutral but Uneven Charge Distribution):
• Aliphatic Hydroxyl Side Chains: Contain hydroxyl (-OH) groups that make the side chains polar and reactive
• Properties: Hydrophilic; capable of hydrogen bonding.
o Serine (Ser, S): Derived from alanine; has a hydroxyl group.
o Threonine (Thr, T): Derived from valine; has a hydroxyl group.
o Tyrosine (Tyr, Y): Derived from phenylalanine; contains a hydroxyl group on an aromatic ring.
• Sulfur-Containing Side Chains:
o Cysteine (Cys, C): Contains a sulfhydryl (-SH) group, highly reactive, can form disulfide bonds.
o Methionine (Met, M): Discussed earlier; contains a thioether group.
• Amide Derivatives: Contain carboxamide groups.
• Properties: Hydrophilic; participate in hydrogen bonding.
o Asparagine (Asn, N): Derived from aspartic acid; contains a carboxamide.
o Glutamine (Gln, Q): Derived from glutamic acid; contains a carboxamide.
Positively Charged Amino Acids (Basic Side Chains):
• Properties: Hydrophilic; often found on protein surfaces.
o Lysine (Lys, K): Contains an amino group at the end of a long aliphatic chain.
o Arginine (Arg, R): Contains a guanidinium group.
o Histidine (His, H): Contains an imidazole ring, which can be positively charged or neutral depending on pH (important for enzyme
activity).
Negatively Charged Amino Acids (Acidic Side Chains):
• Properties: Hydrophilic; can participate in ionic interactions and proton donation.
o Aspartic Acid (Asp, D): Contains a carboxyl group (-COO⁻).
o Glutamic Acid (Glu, E): Like aspartic acid but with a longer chain.
Summary of Classification Table:
Class Examples Key features
Hydrophobic Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp Nonpolar; aliphatic or aromatic side chains;
tend to cluster inside proteins (hydrophobic
effect).
Polar (Neutral) Ser, Thr, Tyr, Cys, Asn, Gln Polar groups (e.g., -OH, -SH, -CONH2);
hydrogen bonding; hydrophilic.
Positively Charged Lys, Arg, His Basic side chains; positively charged at
physiological pH; hydrophilic.
Negatively Charged Asp, Glu Acidic side chains; negatively charged at
physiological pH; hydrophilic.
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, Learning goal: Give the name and one-letter and three-letter symbols of each amino acid. Describe each amino acid in terms of size, charge,
hydrogen-bonding capacity, chemical reactivity, and hydrophilic or hydrophobic properties.
Answer:
Hydrophobic Amino Acids:
• Nonpolar Aliphatic Side Chains:
o Glycine (Gly, G): Smallest, achiral; hydrophobic.
o Alanine (Ala, A): Small; methyl group.
o Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I): Larger, branched; hydrophobic.
o Methionine (Met, M): Contains a thioether (-S-) group; hydrophobic.
o Proline (Pro, P): Cyclic; creates rigidity; hydrophobic.
• Aromatic Side Chains:
o Phenylalanine (Phe, F): Nonpolar aromatic ring; hydrophobic.
o Tryptophan (Trp, W): Contains an indole ring; hydrophobic but has some hydrogen-bonding capacity (NH group).
Polar Amino Acids (Neutral Overall):
• Aliphatic Hydroxyl Groups:
o Serine (Ser, S): Small, -OH group; participates in hydrogen bonding.
o Threonine (Thr, T): Like valine but with -OH group; hydrogen bonding.
o Tyrosine (Tyr, Y): Large aromatic with -OH; hydrophilic.
• Sulfur-Containing:
o Cysteine (Cys, C): -SH group; reactive; forms disulfide bonds.
• Amide Derivatives:
o Asparagine (Asn, N) and Glutamine (Gln, Q): Terminal -CONH2 groups; hydrophilic; hydrogen bonding.
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Learning goal: Distinguish between the Fischer projection and stereochemical rendering of molecules.
Answer: A Fischer projection is used when it's more important to visualize the constituent atoms (like carbons,
hydrogens, and other atoms) in a molecule rather than its shape.
The projection represents bonds around a central carbon atom using horizontal and vertical lines:
• Horizontal bonds project out of the page toward the viewer.
• Vertical bonds project behind the page, away from the viewer.
Every atom is explicitly identified, making it easier to understand the connectivity and arrangement of atoms in the molecule.
Stereochemical rendering focuses on the shape of the molecule, which is crucial for understanding its function.
These diagrams simplify the depiction by:
• Not explicitly showing all carbon and hydrogen atoms (unless they are functionally important).
• Highlighting functional groups, which are key to the molecule’s activity.
Bonds are shown using a combination of:
• Solid wedges: Bonds coming out of the page toward the viewer.
• Dashed wedges: Bonds going into the page away from the viewer.
• Straight lines: Bonds lying in the plane of the page.
Key Differences:
Aspect Fischer Projection Stereochemical Rendering
Purpose Visualizing constituent atoms and connectivity. Understanding the shape and function.
Detail Explicitly shows all atoms (e.g., carbons, hydrogens). Omits some atoms for simplicity (focus on function).
Bond Representation Horizontal/vertical lines for bonds. Wedges and straight lines to depict 3D structure.
Emphasis Atomic structure and arrangement. Molecular shape and activity.
Learning goal: Understand the chirality of amino acids.
Answer: Amino acids are chiral molecules because their central carbon atom (the α-carbon) is bonded to four different groups:
• An amino group (-NH2 or NH3⁺),
• A carboxylic acid group (-COOH or COO⁻),
• A hydrogen atom (H),
• A side chain (R group).
This arrangement makes them tetrahedral and capable of existing as two mirror-image isomers: L isomer and D isomer.
Learning goal: Know that proteins only contain L amino acids.
Answer: Although both L and D forms of amino acids are theoretically possible, only L amino acids
are used in the synthesis of proteins in biological systems. However, the reason for this preference
remains unclear. A possible explanation is that L amino acids have a slightly higher solubility than
their racemic DL mixtures, which could have been amplified over time in evolutionary processes
1|P a g e
,Learning goal: Draw the structure of an amino acid and indicate the following features that are common to all amino acids: functional groups,
side chains, and ionic forms.
Answer: An α-amino acid has the following structure:
1. Functional groups:
• Amino group (-NH3⁺ at physiological pH).
• Carboxyl group (-COO⁻ at physiological pH).
2. Side chain (R group):
• This is the variable group that differs among the 20 amino acids and determines their unique properties.
3. Ionic forms:
• At neutral pH (~7), amino acids exist as zwitterions (dipolar ions):
o The amino group is protonated (NH3⁺).
o The carboxyl group is deprotonated (COO⁻).
• At low pH, both groups are protonated:
o NH3⁺ and -COOH.
• At high pH, both groups lose their protons:
o NH2 and COO⁻.
Question 1: Here is the amino acid Leucine displayed. Is the amino acid shown D or L? Is naturally occurring Leucine D or L?
Answer: The amino acid shown is L and naturally occurring Leucine is also L. All amino acids in proteins are L isomers.
Question 2: Some molecules contain both positive and negative charges but overall have a neutral charge, like leucine. What
are these molecules called?
a. Enantiomers
b. Amino acid
c. Racemate
d. Zwitterion
e. Amphipath
Answer: Zwitterion.
Question 3: Valine is an amino acid that can exist as a zwitterion. What is the charge of valine at the following pH
values? pH-values: pH = 0, pH = 6 and pH = 14.
Answer: The amino group and the carboxyl group can give charge to the amino acid. Think if they are protonated or
not at the given pH. pH = 0 → +1; pH = 6 → 0; pH = 14 → -1.
3.2 Amino Acids Contain a Wide Array of Functional Groups
Learning goal: Classify each of the 20 amino acids according to the side chain on the α-carbon as aliphatic, aromatic, sulfur-containing, aliphatic
hydroxyl, basic, acidic, or amide derivative.
Answer:
Hydrophobic Amino Acids (Nonpolar R Groups):
• Aliphatic Side Chains: Hydrocarbon chains that are nonpolar and hydrophobic.
• Properties: Hydrophobic; tend to cluster together in the interior of proteins (hydrophobic effect).
o Glycine (Gly, G): Simplest amino acid; R group is a hydrogen atom. Unique: Achiral.
o Alanine (Ala, A): Contains a methyl group (-CH3).
o Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I): Branched hydrocarbon side chains.
o Methionine (Met, M): Contains a thioether group (-S-) in a largely aliphatic chain.
o Proline (Pro, P): Has a cyclic structure where the side chain is bonded to both the α-carbon and the amino nitrogen, creating
conformational restrictions.
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,Hydrophobic Amino Acids (Nonpolar R Groups):
• Aromatic Side Chains: Contain ring structures with delocalized π-electrons.
• Properties: Hydrophobic; tend to cluster together in the interior of proteins (hydrophobic effect).
o Phenylalanine (Phe, F): Contains a phenyl group attached to an aliphatic chain.
o Tryptophan (Trp, W): Contains an indole group (two fused rings, one with NH).
Polar Amino Acids (Neutral but Uneven Charge Distribution):
• Aliphatic Hydroxyl Side Chains: Contain hydroxyl (-OH) groups that make the side chains polar and reactive
• Properties: Hydrophilic; capable of hydrogen bonding.
o Serine (Ser, S): Derived from alanine; has a hydroxyl group.
o Threonine (Thr, T): Derived from valine; has a hydroxyl group.
o Tyrosine (Tyr, Y): Derived from phenylalanine; contains a hydroxyl group on an aromatic ring.
• Sulfur-Containing Side Chains:
o Cysteine (Cys, C): Contains a sulfhydryl (-SH) group, highly reactive, can form disulfide bonds.
o Methionine (Met, M): Discussed earlier; contains a thioether group.
• Amide Derivatives: Contain carboxamide groups.
• Properties: Hydrophilic; participate in hydrogen bonding.
o Asparagine (Asn, N): Derived from aspartic acid; contains a carboxamide.
o Glutamine (Gln, Q): Derived from glutamic acid; contains a carboxamide.
Positively Charged Amino Acids (Basic Side Chains):
• Properties: Hydrophilic; often found on protein surfaces.
o Lysine (Lys, K): Contains an amino group at the end of a long aliphatic chain.
o Arginine (Arg, R): Contains a guanidinium group.
o Histidine (His, H): Contains an imidazole ring, which can be positively charged or neutral depending on pH (important for enzyme
activity).
Negatively Charged Amino Acids (Acidic Side Chains):
• Properties: Hydrophilic; can participate in ionic interactions and proton donation.
o Aspartic Acid (Asp, D): Contains a carboxyl group (-COO⁻).
o Glutamic Acid (Glu, E): Like aspartic acid but with a longer chain.
Summary of Classification Table:
Class Examples Key features
Hydrophobic Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp Nonpolar; aliphatic or aromatic side chains;
tend to cluster inside proteins (hydrophobic
effect).
Polar (Neutral) Ser, Thr, Tyr, Cys, Asn, Gln Polar groups (e.g., -OH, -SH, -CONH2);
hydrogen bonding; hydrophilic.
Positively Charged Lys, Arg, His Basic side chains; positively charged at
physiological pH; hydrophilic.
Negatively Charged Asp, Glu Acidic side chains; negatively charged at
physiological pH; hydrophilic.
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, Learning goal: Give the name and one-letter and three-letter symbols of each amino acid. Describe each amino acid in terms of size, charge,
hydrogen-bonding capacity, chemical reactivity, and hydrophilic or hydrophobic properties.
Answer:
Hydrophobic Amino Acids:
• Nonpolar Aliphatic Side Chains:
o Glycine (Gly, G): Smallest, achiral; hydrophobic.
o Alanine (Ala, A): Small; methyl group.
o Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I): Larger, branched; hydrophobic.
o Methionine (Met, M): Contains a thioether (-S-) group; hydrophobic.
o Proline (Pro, P): Cyclic; creates rigidity; hydrophobic.
• Aromatic Side Chains:
o Phenylalanine (Phe, F): Nonpolar aromatic ring; hydrophobic.
o Tryptophan (Trp, W): Contains an indole ring; hydrophobic but has some hydrogen-bonding capacity (NH group).
Polar Amino Acids (Neutral Overall):
• Aliphatic Hydroxyl Groups:
o Serine (Ser, S): Small, -OH group; participates in hydrogen bonding.
o Threonine (Thr, T): Like valine but with -OH group; hydrogen bonding.
o Tyrosine (Tyr, Y): Large aromatic with -OH; hydrophilic.
• Sulfur-Containing:
o Cysteine (Cys, C): -SH group; reactive; forms disulfide bonds.
• Amide Derivatives:
o Asparagine (Asn, N) and Glutamine (Gln, Q): Terminal -CONH2 groups; hydrophilic; hydrogen bonding.
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