Amino Acids: Structure, Stereochemistry, Classification, and Properties

Amino Acids

Introduction

Amino acids are the fundamental building blocks of proteins and play essential roles in biochemistry. They possess a central carbon atom (the α-carbon) bonded to an amino group, a carboxylic acid group, a hydrogen atom, and a unique side chain (R group).

Structure of an α-Amino Acid

Chemical Structure

• α-Carbon: The central carbon atom to which four different groups are attached: amino group (–NH2), carboxylic acid group (–COOH), hydrogen atom, and a side chain (R group).

• Zwitterion Formation: At neutral pH, the amino group is protonated (–NH3+) and the carboxylic acid group is deprotonated (–COO−), resulting in a molecule with both positive and negative charges, called a zwitterion.

• General Formula: $\mathrm{H_2N{-}CHR{-}COOH}$

Example: Glycine is the simplest amino acid, with R = H.

Stereochemistry of Amino Acids

Chirality and Stereocenters

• When four different groups are attached to the α-carbon, it becomes a chiral center (stereocenter or asymmetric carbon).

• All common amino acids except glycine (where R = H) are chiral.

• Amino acids exist as enantiomers: L- and D-forms. Proteins are composed almost exclusively of L-amino acids.

• Fischer Projection: A two-dimensional representation used to depict stereochemistry.

Example: L-alanine and D-alanine are mirror images and enantiomers.

Classification of Naturally Occurring Amino Acids

Categories Based on Side Chain Properties

• Nonpolar Aliphatic Amino Acids: Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Isoleucine (Ile)

• Nonpolar Aromatic Amino Acids: Phenylalanine (Phe), Tyrosine (Tyr), Tryptophan (Trp)

• Sulfur-Containing Amino Acids: Methionine (Met), Cysteine (Cys)

• Polar Uncharged Amino Acids: Serine (Ser), Threonine (Thr), Asparagine (Asn), Glutamine (Gln)

• Positively Charged (Basic) Amino Acids: Lysine (Lys), Arginine (Arg), Histidine (His)

• Negatively Charged (Acidic) Amino Acids: Aspartic acid (Asp), Glutamic acid (Glu)

Category	Amino Acids	Side Chain Properties
Nonpolar Aliphatic	Gly, Ala, Val, Leu, Ile	Hydrophobic, aliphatic chains
Nonpolar Aromatic	Phe, Tyr, Trp	Aromatic rings, absorb UV light
Sulfur-Containing	Met, Cys	Contains sulfur atom
Polar Uncharged	Ser, Thr, Asn, Gln	Hydrophilic, uncharged
Positively Charged	Lys, Arg, His	Basic, positively charged at physiological pH
Negatively Charged	Asp, Glu	Acidic, negatively charged at physiological pH

Example: Tyrosine and tryptophan are aromatic amino acids that absorb UV light.

General Properties of Amino Acids

Absorption Spectra

• Aromatic amino acids (tyrosine and tryptophan) absorb light in the near-ultraviolet region (around 280 nm).

• This property is used to quantify proteins by measuring UV absorbance.

• Nucleic acids absorb most strongly at 260 nm.

Ionization and pKa Values

• Amino acids contain ionizable groups (amino, carboxyl, and sometimes side chains) with characteristic pKa values.

• Typical pKa ranges:

  • α-carboxyl group: 2.0–2.5

  • α-amino group: 9.0–9.5

  • Side chains (e.g., Asp, Glu, Lys, Arg, Cys, Tyr, His): variable, see table below

Group	pKa Range
α-carboxyl (Asp, Glu)	2.0–2.5
α-amino (Lys)	9.0–9.5
Side chain (Cys)	8.5–9.0
Side chain (Tyr)	9.5–10.5
Side chain (His)	6.0–7.0
Side chain (Arg)	12.0–12.5

Example: The titration curve of histidine shows three distinct ionization steps corresponding to its groups.

Translational Modifications

• Amino acids can be modified after translation, affecting protein function, signaling, structure, and gene expression.

• Examples include phosphorylation, acetylation, methylation, and carboxylation.

Example: N-acetyllysine is a lysine residue modified by acetylation.

Peptides and the Peptide Bond

Peptide Bond Formation

• Peptide bonds form via condensation reactions between the amino group of one amino acid and the carboxyl group of another, releasing water.

• This reaction is not thermodynamically favorable and is coupled to ATP hydrolysis during protein synthesis.

• General reaction: $\mathrm{Amino\ Acid_1 + Amino\ Acid_2 \rightarrow Dipeptide + H_2O}$

Structure and Properties of the Peptide Bond

• The peptide bond is planar and stable due to resonance delocalization of electrons.

• Peptide chains have directionality: N-terminus (amino end) to C-terminus (carboxyl end).

Peptide Bond Cleavage

• Peptide bonds can be hydrolyzed by strong acid at high temperature or by specific enzymes called proteases.

• Proteases have sequence specificity, cleaving peptide bonds at particular amino acid residues.

Protease	Cleavage Specificity
Trypsin	After Lys or Arg
Chymotrypsin	After Phe, Tyr, or Trp
Cyanogen Bromide	After Met
Additional info: Other proteases may have different specificities.

Peptides: Oligopeptides and Polypeptides

Definitions and Structure

• Oligopeptides: Peptide chains with typically 2–15 amino acid residues.

• Polypeptides: Chains with more than 15 residues; proteins are composed of one or more polypeptides.

• Peptides can have modified N- or C-termini, such as acetylation or amidation.

Peptides and Proteins as Polyampholytes

Ionization Behavior

• Peptides and proteins contain multiple ionizable groups, making them polyampholytes (molecules with both acidic and basic groups).

• The net charge of a peptide depends on the pH of the solution.

• As pH increases, the overall charge becomes more negative; as pH decreases, it becomes more positive.

• The isoelectric point (pI) is the pH at which the net charge is zero.

Example: The titration curve of a tetrapeptide shows stepwise ionization of its groups.

Additional info: These notes summarize the foundational concepts of amino acid structure, classification, stereochemistry, and peptide chemistry, which are essential for understanding protein biochemistry.