Amino acids are the building blocks of life, best known for their role in constructing proteins. However, amino acids exist in different structural forms with distinct properties and functions. Understanding these variations is a starting point for appreciating their full scope in the biological world.
The Concept of Chirality in Amino Acids
An amino acid’s architecture determines its function, and a central concept to this structure is chirality. Chirality is a property of asymmetry, much like a person’s left and right hands. While they are mirror images of each other, they cannot be perfectly superimposed. This principle applies to all amino acids except for the simplest one, glycine.
All other amino acids exist in two distinct forms, known as stereoisomers or enantiomers. These forms are designated as either L-amino acids (from the Latin levo, for left) or D-amino acids (from the Latin dextro, for right). The functional groups attached to a central carbon atom are arranged differently in space for each enantiomer.
For much of biological history, it was believed that life almost exclusively utilized the L-form. The cellular machinery that synthesizes proteins, the ribosome, is specifically configured to recognize and incorporate L-amino acids. This is why L-amino acids are often referred to as “proteinogenic.” The D-form was largely considered a biological rarity, though this perspective has shifted as research uncovered their specific roles in nature.
Natural Occurrence of D-Amino Acids
D-amino acids are found in a variety of natural settings. One of their most significant locations is within the cell walls of bacteria. These structures contain a polymer called peptidoglycan, where D-alanine and D-glutamate are components of peptide chains that make the wall resistant to enzymes designed to break down L-amino acid chains.
Beyond the microbial world, D-amino acids have been identified in a range of organisms and environments, including:
- The venom of certain animals, such as snails and spiders
- Some marine invertebrates
- Fermented foods and beverages, produced by microorganisms
- The central nervous system of mammals, including humans
In mammals, specific D-amino acids like D-serine and D-aspartate are found in the brain. They are also detected in tissues with slow protein turnover, such as the eye lens, teeth, and skin, where their presence often increases with age.
Biological Roles and Functions
In bacteria, their role is structural. The inclusion of D-alanine and D-glutamate in peptidoglycan creates a robust cell wall that can withstand internal turgor pressure and resist enzymatic attack. The enzymes that produce these D-amino acids are specific to bacteria.
In mammals, the functions of D-amino acids are regulatory. D-serine, for instance, acts as a neuromodulator in the brain. It binds to N-methyl-D-aspartate (NMDA) receptors on nerve cells to help regulate the strength and duration of nerve signals. This process is fundamental to learning, memory, and brain plasticity.
D-aspartate also functions as a signaling molecule in the nervous and endocrine systems, influencing hormone production and release. The accumulation of D-amino acids in long-lived proteins, such as those in the eye lens and brain, is also an area of research. This gradual conversion from L- to D-forms occurs over time and is thought to contribute to age-related changes in tissue, potentially linking them to conditions like cataracts.
Applications in Technology and Health
The presence of D-amino acids in bacterial cell walls is a target for antibiotic development. Many antibiotics, like penicillin and vancomycin, work by interfering with the synthesis or incorporation of D-amino acids into the peptidoglycan layer. This disruption weakens the cell wall, leading to bacterial death while leaving mammalian cells unharmed.
The presence of D-amino acids in the human body has also led to their use as biomarkers. Changes in the levels of specific D-amino acids in blood or cerebrospinal fluid can indicate certain diseases. For example, altered concentrations of D-serine have been linked to neurological disorders like schizophrenia and Alzheimer’s disease, and monitoring these levels could aid in diagnosis and treatment.
Beyond medicine, D-amino acids are used in the food industry as flavor enhancers or as components of artificial sweeteners. Their resistance to degradation by common enzymes also makes them useful in creating more stable peptide-based drugs. By substituting an L-amino acid with its D-counterpart in a therapeutic peptide, its lifespan in the body can be extended, improving its efficacy.