Before the emergence of life on primitive earth, left-handed amino acids (L-enantiomers) prevailed as the building blocks of proteins and right-handed amino acids (D-enantiomers) were eliminated. Nevertheless, D-amino acids have been recently found in higher living organisms in the form of free amino acids, peptides, and proteins.
    Free D-serine functions as a co-agonist of the NMDA receptor and as an endogenous synaptic modulator. Free D-aspartic acid (D-Asp) functions in the inhibition of melatonin secretion, release of prolactin, and synthesis of testosterone. Enzymes that synthesize and degrade D-amino acids have also been detected in a wide variety of organisms.
     D-Amino acid-containing peptides have been found in both vertebrates and invertebrates. These peptides are well known as opioid peptides. Dermorphin is the first example of a D-amino acid-containing peptide found in vertebrates. It was isolated from the skin secretions of a frog and is an opioid peptide comprising seven amino acid residues, of which the second is D-alanine (D-Ala). Its biological activity is about 1000 times greater than that of morphine, and is lost by substituting L-Ala for D-Ala, indicating that D-Ala is essential.
     D-Amino acids are also found in proteins related to aging. Although proteins consist exclusively of L-amino acids, D-Asp has been detected in various tissues from elderly individuals. D-Asp occurs as a result of the racemization of Asp residues in the protein over time inasmuch as the proteins in such tissues are metabolically inert. D-Asp residues in lens and in brain are related to cataract and Alzheimer's disease, respectively.
     The remarkable progress of D-amino acid research is due to the continuing improvements in analytical methods. Today, we cannot describe life science without mentioning D-amino acids. We would like to co-operate with scientists from all over the world to further develop D-amino acid research.

May 2016
Committee of D-Amino Acid Research Society