Amino Acids, Peptides, and Proteins: Structures, Properties, and Acid-Base Chemistry

Module 3: Amino Acids, Peptides and Proteins

Objectives

This module introduces the foundational concepts of amino acids, their chemical properties, and their role in protein structure and function. Students will learn to compare amino acid structures, construct titration curves, determine net charge at any pH, and calculate isoelectric points.

• Compare the structures and properties of the amino acids.

• Construct titration curves for the amino acids.

• Determine the net charge of any amino acid at any pH.

• Calculate isoelectric points for the amino acids.

Amino Acids

General Properties

Amino acids are the building blocks of proteins, which are linear polymers with unique sequences and lengths. All living organisms use the same 20 standard amino acids to construct proteins, allowing for immense diversity in protein structure and function.

• Proteins are composed of amino acids linked in a specific order.

• With 20 amino acids, even short peptides can have thousands of possible sequences (e.g., a tripeptide: 203 = 8000 combinations).

• A protein of 100 residues has 1.3 × 10130 possible sequences.

Proteins as Polymers of Amino Acids

Proteins are formed by joining amino acids through peptide bonds, resulting in a linear chain. This polymerization offers several advantages:

• Simplicity: One type of reaction for polymerization and another for degradation, regardless of amino acid identity.

• Recycling: Proteins can be broken down into reusable amino acid building blocks.

• Diversity: The combination of 20 amino acids allows for a vast array of protein sequences and functions.

Peptide bond formation:

$ext{Amino acid}_1 + ext{Amino acid}_2 ightarrow ext{Dipeptide} + H_2O$

General Structure of Amino Acids

All amino acids share a common structure:

• Alpha carbon (Cα): Central carbon atom.

• Amino group (NH3+): Basic group.

• Carboxyl group (COO-): Acidic group.

• Hydrogen atom (H):

• Side chain (R group): Unique to each amino acid, determines its properties.

Chirality

For 19 of the 20 amino acids, the alpha carbon is attached to four different groups, making it a chiral center. Glycine is the exception, as its side chain is a hydrogen atom, rendering it achiral.

• Stereoisomers: Amino acids exist as L and D isomers; biological proteins use almost exclusively the L isomer.

Classification of Amino Acids by Side Chain Properties

Amino acids are grouped based on the chemical nature of their side chains:

• Non-polar aliphatic

• Aromatic

• Polar, uncharged

• Polar, positively charged

• Polar, negatively charged

These groupings are useful for comparison but are not absolute; other valid classifications exist.

Nonpolar, Aliphatic Amino Acids

Properties

Non-polar side chains lack charge and hydrogen bonding capability. These residues are often found buried in the hydrophobic core of proteins.

• Glycine (Gly, G): Smallest amino acid, not chiral.

• Proline (Pro, P): Often found at polypeptide turns.

• Methionine (Met, M): Contains a sulfur atom in its side chain.

Examples

• Glycine

• Alanine

• Valine

• Leucine

• Isoleucine

• Proline

• Methionine

Aromatic Amino Acids

Properties

Aromatic amino acids contain ring structures in their side chains. Histidine can also be considered aromatic due to its imidazole ring.

• Tyrosine (Tyr, Y): Can be phosphorylated post-translationally, regulating protein function.

• Phenylalanine (Phe, F)

• Tryptophan (Trp, W): Precursor of serotonin, sometimes used as a supplement to promote sleep.

Post-translational Modification

• Phosphorylation: Addition of a phosphate group to hydroxyl-containing amino acids (Tyr, Ser, Thr) by kinases; removal by phosphatases.

Polar, Uncharged Amino Acids

Properties

Polar, uncharged side chains can form hydrogen bonds but do not carry a net charge at physiological pH.

• Serine (Ser, S)

• Threonine (Thr, T): Both can be phosphorylated.

• Asparagine (Asn, N)

• Glutamine (Gln, Q)

• Cysteine (Cys, C): Can form disulfide bonds, stabilizing protein structure.

Disulfide Bonds

Formation and Importance

Disulfide bonds are covalent linkages formed between the sulfhydryl groups of two cysteine residues, stabilizing protein structure. These bonds can be intra- or intermolecular.

Polar, Positively Charged Amino Acids

Properties

These amino acids have side chains that carry a positive charge at physiological pH and can participate in hydrogen bonding.

• Lysine (Lys, K)

• Arginine (Arg, R)

• Histidine (His, H): Imidazole group has a pKa near physiological pH, allowing it to act as a proton donor/acceptor in enzymatic reactions.

Polar, Negatively Charged Amino Acids

Properties

These amino acids have side chains that carry a negative charge at physiological pH and can form hydrogen bonds.

• Aspartate (Asp, D)

• Glutamate (Glu, E): Responsible for the umami taste; used as a flavor enhancer (MSG).

Acid/Base Properties of Amino Acids

Ionizable Groups and pKa Values

Each amino acid contains at least two ionizable groups: the carboxyl and amino groups. Some amino acids have additional ionizable side chains (Lys, Arg, Asp, Glu, Cys, Tyr).

• Diprotic amino acids: Two buffering regions (carboxyl and amino groups).

• Triprotic amino acids: Three buffering regions (including ionizable side chain).

pKa: The pH at which an ionizable group is 50% protonated and 50% deprotonated.

Titration Curves

Amino acids exhibit characteristic titration curves due to their ionizable groups:

• Carboxyl group: pKa ≈ 2.0

• Amino group: pKa ≈ 9.0-10.0

At physiological pH (~7.4), amino acids exist as zwitterions (both groups ionized: COO- and NH3+).

Isoelectric Point (pI)

The isoelectric point (pI) is the pH at which the net charge of the amino acid is zero. For diprotic amino acids:

$pI = rac{pK_{a1} + pK_{a2}}{2}$

Example: Glycine

• pKa1 (carboxyl) = 2.34

• pKa2 (amino) = 9.60

• $pI = rac{2.34 + 9.60}{2} = 5.97$

Example: Glutamate

• pKa1 (carboxyl) = 2.19

• pKa2 (side chain) = 4.25

• $pI = rac{2.19 + 4.25}{2} = 3.22$

Example: Histidine

• pKa1 (carboxyl) = 1.80

• pKa2 (side chain) = 6.00

• pKa3 (amino) = 9.17

• $pI = rac{6.00 + 9.17}{2} = 7.59$

Summary Table: Amino Acid Groupings

Group	Examples	Key Properties
Non-polar, Aliphatic	Gly, Ala, Val, Leu, Ile, Pro, Met	Hydrophobic, often buried in protein core
Aromatic	Phe, Tyr, Trp	Ring structures, absorb UV, can be phosphorylated (Tyr)
Polar, Uncharged	Ser, Thr, Asn, Gln, Cys	Hydrogen bonding, some can be phosphorylated or form disulfide bonds
Polar, Positively Charged	Lys, Arg, His	Basic, carry +1 charge at physiological pH
Polar, Negatively Charged	Asp, Glu	Acidic, carry -1 charge at physiological pH

Additional info: The notes have been expanded to include definitions, examples, and equations for isoelectric point calculation, as well as a summary table for amino acid classification.