Amino acids possess a property known as chirality, which describes a molecule that cannot be perfectly superimposed on its mirror image. These mirror-image molecules are designated as L (Levo) or D (Dextro) forms, a distinction that has profound consequences for the chemistry of life.
Understanding L and D Forms
The chemical basis for this handedness lies at the alpha carbon atom at the center of the amino acid structure. This carbon is bonded to four different chemical groups: an amino group, a carboxyl group, a hydrogen atom, and a variable side chain (R group). Because these four groups are distinct, the alpha carbon functions as a chiral center, allowing the molecule to exist as two stereoisomers, or enantiomers.
These two forms are mirror images, like a person’s left and right hands. The L and D designations are determined by comparing the amino acid’s structure to a reference molecule, glyceraldehyde, using a specific projection method. This structural L or D designation is not based on how the molecule rotates polarized light, despite the historical names Levo (left) and Dextro (right). The only common amino acid without this chiral center is glycine, since its R group is a second hydrogen atom, making it an achiral molecule.
The Rule: L-Amino Acids in Life
Nearly all amino acids incorporated into proteins are of the L configuration. The machinery of the cell, including the ribosomes responsible for protein synthesis, is specifically engineered to exclusively recognize and utilize L-amino acids. This preference for one mirror image is known as biological homochirality.
The adherence to L-amino acids is required for proteins to fold correctly into their precise three-dimensional shapes. A protein’s function is dependent on this native conformation. Substituting even a single L-amino acid with its D-counterpart would fundamentally disrupt the helical and sheet structures that stabilize the final folded protein.
Most enzymes are geometrically tailored to interact only with L-amino acid substrates. The active site of an enzyme fits the L-form of a molecule. An enzyme designed to cleave an L-amino acid chain would be unable to recognize or efficiently process a chain containing a D-amino acid.
The Exception: Roles of D-Amino Acids
D-amino acids play important roles in specific cellular contexts. One well-studied exception occurs in bacteria, where D-alanine and D-glutamic acid are incorporated into the cell wall. These D-forms are components of peptidoglycan, a polymer that provides structural rigidity and protection against osmotic pressure.
D-amino acids in peptidoglycan make the bacterial cell wall resistant to most proteases, which break down L-amino acid chains. The enzymes responsible for cross-linking these D-amino acid-containing peptides are targets of certain antibiotics, such as the beta-lactams. Bacteria also synthesize and release D-amino acids, such as D-methionine and D-leucine, which function as signaling molecules to regulate cell wall remodeling and the dispersal of biofilms.
In the mammalian central nervous system, D-amino acids function as signaling molecules. D-serine acts as a co-agonist for the N-methyl-D-aspartate (NMDA) receptor. These receptors are involved in synaptic plasticity, which underlies learning and memory. D-aspartate is another signaling molecule found in the nervous and endocrine systems, where it helps regulate the synthesis and release of various hormones.
The Mystery of Homochirality
The question of why life selected L-amino acids and their mirror-image counterparts, D-sugars, remains an unsolved puzzle in the study of abiogenesis. Chemical reactions in a laboratory typically produce a racemic mixture. The prebiotic Earth likely contained such a balanced mixture, suggesting some external or self-amplifying force must have created the initial bias.
Scientists have proposed several theories to explain the symmetry breaking that led to homochirality. One idea involves external influences, such as circularly polarized light in space, which could have selectively destroyed one enantiomer in molecular clouds. Another theory suggests that chiral contaminants delivered by meteorites may have provided a small initial excess of L-amino acids on Earth.
Certain self-amplifying mechanisms could have taken over after an initial bias was established. Autocatalysis proposes that a chiral molecule that catalyzes its own production while suppressing the formation of its mirror image could rapidly amplify a small starting imbalance.