Free D-aspartate and D-serine in the mammalian brain and periphery

It has long been assumed that L-forms of amino acids exclusively constitute free amino acid pools in mammals. However, a variety of studies in the last decade has demonstrated that free D-aspartate and D-serine occur in mammals and may have important physiological function in mammals. Free D-serine is confined predominantly to the forebrain structure, and the distribution and development of D-serine correspond well with those of the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. As D-serine acts as a potent and selective agonist for the strychnine-insensitive glycine site of the NMDA receptor, it is proposed that D-serine is a potential candidate for an NMDA receptor-related glycine site agonist in mammalian brain. In contrast, widespread and transient emergence of a high concentration of free D-aspartate is observed in the brain and periphery. Since the periods of maximal emergence of D-aspartate in the brain and periphery occur during critical periods of morphological and functional maturation of the organs, D-aspartate could participate in the regulation of these regulation of these developmental processes of the organs. This review deals with the recent advances in the studies of presence of free D-aspartate and D-serine and their metabolic systems in mammals. Since D-aspartate and D-serine have been shown to potentiate NMDA receptor-mediated transmission through the glutamate binding site and the strychnine-insensitive glycine binding site, respectively, and have been utilized extensively as potent and selective tools to study the excitatory amino acid system in the brain, we shall discuss also the NMDA receptor and uptake system of D-amino acids.