Amino Acid Chirality

Stereoisomerism and Enantiomers of the Amino Acids

These are the zwitterion enantiomers of the amino acid alanine. All of the amino acids except glycine exist exhibit chirality.
These are the zwitterion enantiomers of the amino acid alanine. All of the amino acids except glycine exist exhibit chirality. Jü

Amino acids (except for glycine) have a chiral carbon atom adjacent to the carboxyl group (CO2-). This chiral center allows for stereoisomerism. The amino acids form two stereoisomers that are mirror images of each other. The structures are not superimposable on each other, much like your left and right hands. These mirror images are termed enantiomers.

D/L and R/S Naming Conventions for Amino Acid Chirality

There are two important nomenclature systems for enantiomers.

The D/L system is based on optical activity and refers to the Latin words dexter for right and laevus for left, reflecting left- and right-handedness of the chemical structures. An amino acid with the dexter configuration (dextrorotary) would be named with a (+) or D prefix, such as (+)-serine or D-serine. An amino acid having the laevus configuration (levorotary) would be prefaced with a (-) or L, such as (-)-serine or L-serine.

Here are the steps to determine whether an amino acid is the D or L enantiomer:

  1. Draw the molecule as a Fischer projection with the carboxylic acid group on top and side chain on the bottom. (The amine group will not be at the top or bottom.)
  2. If the amine group is located on the right side of the carbon chain, the compound is D. If the amine group is on the left side, the molecule is L.
  3. If you wish to draw the enantiomer of a given amino acid, simply draw its mirror image.

    The R/S notation is similar, where R stands for Latin rectus (right, proper, or straight) and S stands for Latin sinister (left). R/S naming follows the Cahn-Ingold-Prelog rules:

    1. Locate the chiral or stereogenic center.
    2. Assign priority to each group based on the atomic number of the atom attached to the center, where 1 = high and 4 = low.
    1. Determine the direction of priority for the other three groups, in order of high to low priority (1 to 3).
    2. If the order is clockwise, then the center is R. If the order is counterclockwise, then the center is S.

    Although most of chemistry has switched over to the (S) and (R) designators for absolute stereochemistry of enantiomers, the amino acids are most commonly named using the (L) and (D) system.

    Isomerism of Natural Amino Acids

    All amino acids found in proteins occur in the L-configuration about the chiral carbon atom. The exception is glycine because it has two hydrogen atoms at the alpha carbon, which cannot be distinguished from each other except via radioisotope labeling.

    D-amino acids are not naturally found in proteins and are not involved in the metabolic pathways of eukaryotic organisms, although they are important in the structure and metabolism of bacteria. For example, D-glutamic acid and D-alanine are structural components of certain bacterial cell walls. It's believed D-serine may be able to act as a brain neurotransmitter. D-amino acids, where they exist in nature, are produced via post-translational modifications of the protein.

    Regarding the (S) and (R) nomenclature, nearly all amino acids in proteins are (S) at the alpha carbon.

    Cysteine is (R) and glycine is not chiral. The reason cysteine is different is because it has a sulfur atom at the second position of the side chain, which has a larger atomic number than that of the groups at the first carbon. Following the naming convention, this makes the molecule (R) rather than (S).