D-amino acids in the central nervous system in health and disease

Recent evidence has shown that d-amino acids are present in animals and humans in high concentrations and fulfill specific biological functions. In the central nervous system, two d-amino acids, d-serine and d-aspartate, occur in considerable concentrations. d-Serine is synthesized and metabolized endogenously and the same might account for d-aspartate. d-Serine has been studied most extensively and was shown to play a role in excitatory amino acid metabolism, being a co-agonist of the N-methyl-d-aspartate (NMDA) receptor. Insight into d-serine metabolism is relevant for physiological NMDA receptor (NMDAr) activation and for all the disorders associated with an altered function of the NMDAr, such as schizophrenia, ischemia, epilepsy, and neurodegenerative disorders. d-Aspartate appears to play a role in development and endocrine function, but the precise function of d-aspartate and other d-amino acids in animals and humans requires further investigation. As d-amino acids play biological roles, alterations in the concentrations of d-amino acids might occur in some disorders and relate to the pathogenesis of these disorders. d-Amino acid concentrations may then not only help in the diagnostic process, but also provide novel therapeutic targets. Consequently, the presence and important roles of d-amino acids in higher organisms do not only challenge former theories on mammalian physiology, but also contribute to exciting new insights in human disease.