Abstract
D-Amino-acid oxidase (DAO), which metabolizes neutral and basic D-amino acids including D-serine and D-alanine, and serine racemase (SRR), which catalyzes racemization of L-serine to D-serine, are regulatory factors of the intrinsic amounts of D-amino acids in mammals. Both enzymes have been demonstrated to have relation to neuronal diseases such as schizophrenia and amyotrophic lateral sclerosis via the regulation of the intrinsic amounts of neuromodulators of N-methyl-D-aspartate receptors, D-serine and D-alanine. Therefore, the regulators of DAO and SRR are proposed to become novel targets of drugs for changing the intrinsic amounts of D-serine and D-alanine, and the alterations of D-serine and D-alanine amounts following the changes of DAO and SRR activities are expected to be clarified. In this review, we have summarized recent works on the changes of D-serine and D-alanine amounts in mammalian brain tissues and physiological fluids with the decrease of activities of DAO and SRR. The highly sensitive and selective two-dimensional high-performance liquid chromatographic system for the determination of small amounts of D-amino acids in mammals has also been introduced.