Amino Acids: Properties, Structures, and Peptide Bonds

Amino Acids: Properties and Structures

Introduction to Amino Acids

Amino acids are the fundamental building blocks of proteins. All proteins are composed primarily of 20 standard amino acids, each with unique properties determined by their side chains (R groups). Understanding their structures, properties, and abbreviations is essential for biochemistry.

• General Structure: Each amino acid contains an α-amino group (–NH2), an α-carboxyl group (–COOH), a hydrogen atom, and a distinctive R group attached to the central (α) carbon.

• R Group: The chemical nature of the R group defines the uniqueness and properties of each amino acid.

• Abbreviations: Amino acids are commonly represented by both 3-letter and 1-letter codes (e.g., Glycine: Gly, G).

Example: Glycine (Gly, G) is the simplest amino acid, with its R group being a hydrogen atom. It is unique in being achiral because its α-carbon has two identical substituents.

Stereoisomerism in Amino Acids

Except for glycine, all amino acids are chiral and exist as two stereoisomers: D and L forms. Proteins in living organisms are composed almost exclusively of L-amino acids.

• Chirality: The α-carbon is a stereocenter (except in glycine).

• Fischer Projection: L- and D- isomers are designated based on their configuration relative to glyceraldehyde.

Example: Alanine exists as both D- and L- isomers, but only the L-form is found in proteins.

Classification of Amino Acids by Properties

Amino acids are classified based on the properties of their side chains:

• Nonpolar (Hydrophobic): Ala, Val, Leu, Ile, Met, Pro, Phe, Trp

• Polar (Hydrophilic): Ser, Thr, Asn, Gln, Cys, Tyr

• Acidic (Negatively Charged): Asp, Glu

• Basic (Positively Charged): Lys, Arg, His

Hydrophobic amino acids are typically found in the interior of proteins or in membrane-spanning regions, while hydrophilic amino acids are often exposed to aqueous environments.

Essential Amino Acids

Essential amino acids cannot be synthesized by the human body and must be obtained from the diet.

• Essential for humans: Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine (dietary requirement not defined), Arginine (essential for children), Leucine, Lysine

Mnemonic: "PVT TIM HALL" helps remember the essential amino acids.

Special Amino Acids

• Glycine: Achiral, smallest amino acid.

• Cysteine: Contains a sulfhydryl group (–SH), can form disulfide bonds (cystine) important for protein structure.

• Proline: Has a cyclic structure, introduces kinks in polypeptide chains.

• Selenocysteine: The 21st amino acid, found in some proteins, contains selenium instead of sulfur.

Ionization and Titration of Amino Acids

Ionizable Groups and Zwitterions

Amino acids can exist in different ionic forms depending on the pH of the environment. At physiological pH (~7.4), most amino acids exist as zwitterions, with a positively charged amino group and a negatively charged carboxyl group.

• pKa Values: The pKa of the α-carboxyl group is typically around 2, and the α-amino group around 9-10. Side chains of some amino acids also have ionizable groups with characteristic pKa values.

• Zwitterion: At pH 7, the amino acid has no net charge but contains both positive and negative charges.

Equation:

$\text{Amino acid (zwitterion):} \quad ^{+}NH_3-CHR-COO^{-}$

Titration Curves

The titration curve of an amino acid shows how its charge changes with pH. The isoelectric point (pI) is the pH at which the amino acid has no net charge.

• pI Calculation (for amino acids without ionizable side chains):

$pI = \frac{pK_{a,1} + pK_{a,2}}{2}$

For amino acids with ionizable side chains, the pI is the average of the two pKa values that surround the neutral species.

Functional Groups and Their Acid-Base Properties

• Carboxyl group (–COOH): Acidic, loses a proton at low pH.

• Amino group (–NH2): Basic, gains a proton at low pH.

• Side chains: Some (e.g., Asp, Glu, Lys, Arg, His, Cys, Tyr) have ionizable groups with specific pKa values.

Peptide Bonds and Protein Structure

Formation and Properties of Peptide Bonds

A peptide bond is formed by a condensation reaction between the α-carboxyl group of one amino acid and the α-amino group of another, releasing water.

• Amide Bond: The peptide bond is a type of amide bond.

• No Free Rotation: Due to partial double-bond character, there is no free rotation around the C–N peptide bond.

• Planarity: The peptide bond is planar, and the atoms involved are coplanar.

• Dipole Moment: The peptide bond has a significant dipole moment due to the difference in electronegativity between the oxygen and nitrogen atoms.

Equation:

$\text{Peptide bond formation:} \quad \ce{H_2N-CHR-COOH + H_2N-CHR'-COOH \rightarrow H_2N-CHR-CO-NH-CHR'-COOH + H_2O}$

Levels of Protein Structure

• Primary Structure: The linear sequence of amino acids in a protein, written from the N-terminus (free amino group) to the C-terminus (free carboxyl group).

• Secondary, Tertiary, Quaternary: Higher levels of protein structure involve folding and assembly of the polypeptide chain(s).

Peptide Classification

• Peptides: Polymers of amino acids less than 12 residues in length.

• Oligopeptides: About 12 residues in length.

• Polypeptides: Greater than 12 residues in length.

Number of Unique Peptide Sequences

• Tripeptides: $20^3 = 8,000$ unique sequences

• Tetrapeptides: $20^4 = 160,000$ unique sequences

Case Study: Bicarbonate Buffer and Mountain Sickness

Acute Mountain Sickness (AMS) and the Bicarbonate Buffer System

At high altitudes, lower barometric pressure leads to reduced oxygen availability. To compensate, individuals breathe faster, which increases CO2 exhalation and disrupts the bicarbonate buffer system, potentially causing blood pH to rise (alkalosis).

• Bicarbonate Buffer System: Maintains blood pH by balancing CO2 and HCO3− levels.

• Treatment: Drugs that promote renal excretion of bicarbonate help restore acid-base balance by lowering blood pH.

Equation:

$\ce{CO_2 + H_2O <=> H_2CO_3 <=> HCO_3^- + H^+}$

Single-Letter and Three-Letter Codes for Amino Acids

Each amino acid is represented by a standard 3-letter and 1-letter code. Memorizing these codes is essential for interpreting protein sequences.

1-Letter	3-Letter	Name
A	Ala	Alanine
R	Arg	Arginine
N	Asn	Asparagine
D	Asp	Aspartic acid
C	Cys	Cysteine
E	Glu	Glutamic acid
Q	Gln	Glutamine
G	Gly	Glycine
H	His	Histidine
I	Ile	Isoleucine
L	Leu	Leucine
K	Lys	Lysine
M	Met	Methionine
F	Phe	Phenylalanine
P	Pro	Proline
S	Ser	Serine
T	Thr	Threonine
W	Trp	Tryptophan
Y	Tyr	Tyrosine
V	Val	Valine

Summary Table: Amino Acid Classification

Type	Amino Acids
Nonpolar (Hydrophobic)	Ala, Val, Leu, Ile, Met, Pro, Phe, Trp
Polar (Uncharged)	Ser, Thr, Asn, Gln, Cys, Tyr
Acidic (Negatively Charged)	Asp, Glu
Basic (Positively Charged)	Lys, Arg, His

Key Skills for Biochemistry Students

• Identify amino acids from their structures.

• Determine D- or L- configuration.

• Know side chain pKa values to within 0.5 pH units.

• Calculate the charge of a peptide at a given pH.

• Draw the structure of tripeptides and calculate the number of possible unique sequences.

Additional info:

• Some slides referenced textbook sections (Pratt & Cornely) for further reading.

• Case studies and sample questions are used to reinforce understanding of amino acid properties and their physiological relevance.