Core Skeleton
The basic scaffold of every amino acid consists of three components attached to a central carbon atom (the carbon):
- Amino group (NH): A basic functional group that can accept a proton, typically existing as NH at physiological pH.
- Carboxyl group (COOH): An acidic functional group that can donate a proton, usually present as COO under biological conditions.
- Hydrogen atom (H): A single hydrogen bound to the carbon.
These three groups, together with a variable side chain (the R group), define the overall chemical identity of each amino acid.
The R Group (Side Chain)
The side chain, denoted as R, is what differentiates one amino acid from another. It can be as simple as a single hydrogen atom (as in glycine) or a complex aromatic ring (as in tryptophan). The chemistry of the R group determines many of the amino acids properties, including:
- Polarity and solubility
- Charge at physiological pH
- Ability to form hydrogen bonds or participate in hydrophobic interactions
- Potential for covalent modification (e.g., disulfide bond formation)
Based on the nature of the R group, amino acids are commonly classified into several categories:
- Nonpolar (hydrophobic): Leucine, isoleucine, valine, phenylalanine, etc.
- Polar (uncharged): Serine, threonine, asparagine, glutamine.
- Positively charged (basic): Lysine, arginine, histidine.
- Negatively charged (acidic): Aspartic acid, glutamic acid.
- Special cases: Glycine (no side chain) and proline (cyclic side chain that restricts backbone flexibility).
Stereochemistry The Carbon Is Chiral
Except for glycine, the carbon of an amino acid is a stereogenic center, meaning it is attached to four different substituents. This creates two possible enantiomers: L and Dforms. In nature, proteins are built almost exclusively from Lamino acids. The Dforms are found in bacterial cell walls and some peptide antibiotics.
Because the L and Denantiomers are nonsuperimposable, they can have markedly different biological activities. For example, Dserine acts as a neurotransmitter in the brain, while Lserine is a proteinogenic building block.
Ionization and Zwitterion Form
In aqueous solution near neutral pH, an amino acid typically exists as a zwitterion: the amino group is protonated (NH) and the carboxyl group is deprotonated (COO). This internal charge balance gives the molecule no net charge but makes it highly soluble in water.
Two characteristic pK values describe the ionization of the functional groups:
- pK (carboxyl): Usually around 2.02.5. Below this pH the carboxyl group is mostly protonated (COOH).
- pK (amino): Typically between 8.5 and 9.5. Above this pH the amino group loses a proton and becomes NH.
Sidechain ionizable groups have additional pK values (e.g., pK of the guanidinium group in arginine 12.5).
Examples of Common Amino Acids
| Name | Threeletter Code | Oneletter Code | R Group Description |
|---|---|---|---|
| Alanine | Ala | A | Simple methyl group (CH) nonpolar |
| Serine | Ser | S | Hydroxymethyl (CHOH) polar, can form Hbonds |
| Phenylalanine | Phe | F | Benzyl (CHCH) aromatic, hydrophobic |
| Lysine | Lys | K | Aliphatic chain ending in an amino group basic |
| Aspartic acid | Asp | D | Carboxylate side chain acidic |
| Glycine | Gly | G | Hydrogen atom smallest, flexible |
Importance in Protein Structure
The uniform backbone of amino acids (NCC) allows for regular secondary structures such as helices and sheets. Variations in the side chain influence how a polypeptide folds, the stability of the final threedimensional structure, and the proteins functional sites. For instance:
- Hydrophobic side chains tend to cluster in the interior of globular proteins, stabilizing the core.
- Charged residues often appear on the surface, interacting with the aqueous environment or other macromolecules.
- Specific side chains can coordinate metal ions (e.g., cysteine with Zn) or participate in catalysis (e.g., serine in serine proteases).
Beyond the Twenty Proteinogenic Amino Acids
While twenty amino acids are directly encoded by the genetic code, many more exist in nature. Modified residues such as phosphoserine, methylated lysine, and hydroxyproline are generated posttranslationally and expand the functional repertoire of proteins. Synthetic chemistry also provides noncanonical amino acids that can be incorporated into proteins to probe structurefunction relationships or to endow proteins with new properties.
Summary
The general structure of an amino acid consists of an carbon bound to an amino group, a carboxyl group, a hydrogen atom, and a variable R side chain. This scaffold creates a zwitterionic molecule that is soluble in water and capable of forming peptide bonds. The nature of the R group determines the chemical behavior, classification, and role of each amino acid within proteins. Stereochemistry, ionization properties, and sidechain reactivity collectively shape the myriad functions that amino acids perform in living systems.
