Occurrence and functions of free D-aspartate and its metabolizing enzymes

D-Aspartate is one of a few D-amino acids that attracted attention at an early date, since it was detected in various tissues of mammals as a protein component. The occurrence of free D-aspartate in nature was recognized a little later, and raised questions about its physiological functions and metabolism. This amino acid has been gradually accepted, based on various experimental observations, to be a physiological substrate of D-aspartate oxidase, whose role had been considered enigmatic since its early discovery in the 1940s. Mammalian enzymes that serve to liberate D-aspartyl residue in proteins have been identified. One enzyme hydrolyzes peptide bond at the amino side of D-aspartyl residue in a dipeptide and another enzyme hydrolyzes that at the carbonyl side of the residue in proteins. The first pyridoxal 5'-phosphate-dependent aspartate racemase has been purified and cloned from a bivalve species. The enzyme supports the high contents of D-aspartate comparable to those of L-aspartate in the bivalve, and the enantiomers are consumed when hypoxia is imposed on the bivalve. In some yeast species, assimilation of D-aspartate has been found to depend on inducible D-aspartate oxidase, which also serves to detoxify acidic D-amino acids.