Amino acid

Amino acids are organic molecules containing both an amino group and a carboxylic acid group, forming the fundamental building blocks of proteins and participating in numerous biochemical processes essential to life. Although more than 500 amino acids occur in nature, only 22 are recognised as proteinogenic, meaning they are incorporated into proteins by the ribosome and appear in the universal genetic code. These compounds play central roles in metabolism, cellular structure, neurotransmission, and the early chemical evolution of life.

Classification and General Structure

The core structure of an α-amino acid includes an amino group, a carboxyl group, a hydrogen atom, and a variable side chain (R group) all bonded to the α-carbon. The R group determines the chemical behaviour of each amino acid. The standard 22 proteinogenic amino acids assemble into peptides and proteins through ribosomal protein synthesis, while non-proteinogenic amino acids may arise through post-translational modification or by specialised non-ribosomal pathways.
Amino acids are commonly grouped according to shared chemical features:

• By position of the amino group: α-amino acids, β-amino acids, and others.
• By polarity and charge: nonpolar, polar uncharged, acidic, and basic.
• By side-chain type: aliphatic, aromatic, sulphur-containing, and unique-structure groups.

In living organisms, α-amino acids dominate and form the structural basis of proteins. These residues constitute the second-largest component of muscle and other tissues after water.

Naming and Chemical Convention

Formal nomenclature for amino acids, governed by IUPAC–IUBMB recommendations, refers to hypothetical neutral structures in which the amino group is unprotonated and the carboxyl group is undissociated. Although these forms are rarely present under physiological conditions, this convention avoids inconsistency in naming. For example, alanine is systematically named 2-aminopropanoic acid.

Historical Background

The first amino acids were identified in the early nineteenth century. Asparagine was isolated in 1806, followed by cystine in 1810 and glycine and leucine in 1820. The last of the common amino acids to be discovered was threonine in 1935. In 1902, Fischer and Hofmeister independently proposed that proteins consist of long chains of amino acids linked via peptide bonds, transforming biochemical understanding of protein structure. Recognition of amino acids as a coherent chemical class dates from the mid-nineteenth century, and the term “amino acid” entered English usage at the end of that century.

Chirality and Stereochemistry

The α-carbon of most amino acids is a stereogenic centre, giving rise to two enantiomeric forms, designated L and D. Proteinogenic amino acids almost exclusively adopt the L-configuration, mirroring biological homochirality. Glycine is achiral because its side chain is a hydrogen atom. Cysteine, although structurally similar to other amino acids, is assigned the R configuration due to the high atomic number of sulphur affecting its Cahn–Ingold–Prelog priority ranking.
D-amino acids occur naturally in limited contexts, such as bacterial cell walls and certain neuromodulatory molecules, and may also arise from post-translational modifications.

Polar Charged Side Chains

Five amino acids carry a formal charge at physiological pH. Their charged groups often appear on protein surfaces, supporting solubility and stabilising structures through electrostatic interactions known as salt bridges.

• Negatively charged (acidic): aspartate (Asp, D) and glutamate (Glu, E), containing carboxylate groups that generally act as Brønsted acids.
• Positively charged (basic): arginine (Arg, R), lysine (Lys, K), and histidine (His, H). Arginine contains a guanidinium group, while lysine contains a terminal amino group; both are typically protonated. Histidine, with an imidazole side chain of pKₐ around 6.0, is partially protonated at neutral pH and frequently serves as a proton donor or acceptor in catalytic mechanisms.

Polar Uncharged Side Chains

Serine (Ser, S), threonine (Thr, T), asparagine (Asn, N), and glutamine (Gln, Q) possess side chains capable of forming hydrogen bonds. They typically do not ionise under physiological conditions. Threonine contains two stereogenic centres, and its biologically relevant form is 2S,3R-L-threonine.

Hydrophobic Side Chains

Hydrophobic amino acids—including leucine, isoleucine, valine, alanine, methionine, phenylalanine, and others—contain nonpolar side chains that do not readily ionise. Their tendency to avoid water drives protein folding, stabilising the core of globular proteins. Tyrosine is sometimes classed ambiguously because its phenolic group can lose a proton at high pH, but its low aqueous solubility aligns it with hydrophobic residues.

Special Case Side Chains

Some amino acids possess structural features that set them apart:

• Glycine (Gly, G): uniquely flexible owing to its minimal side chain, influencing protein folding and local geometry.
• Cysteine (Cys, C): contains a thiol group capable of forming covalent disulphide bonds critical for protein stability, especially in extracellular proteins and antibodies.
• Proline (Pro, P): has a ring structure linking the side chain to the amino group, making it conformationally restricted and often inducing bends in polypeptide chains.
• Selenocysteine (Sec, U): a rare amino acid incorporated via a specialised translational mechanism, functioning in certain redox-active enzymes.

Biological Roles Beyond Proteins

Amino acids contribute extensively to metabolic and physiological functions. They serve as precursors for neurotransmitters, hormones, nucleotides, and metabolic intermediates. Several amino acids participate in nitrogen transport and pH buffering. Their central role in prebiotic chemistry has also made them subjects of interest in theories of abiogenesis.

Protein Formation and Peptide Bonds

Protein structure arises through the condensation of amino acids into polypeptide chains via peptide bonds, linking the carboxyl group of one residue to the amino group of another. These linear chains fold into complex three-dimensional structures driven by electrostatic interactions, hydrogen bonding, hydrophobic effects, and covalent modifications such as disulphide formation.