Studies on the biosynthetic pathways of D-serine amd D-aspartate in the mammals

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Although D-amino acids have been assumed to be unnatural in mammals, a wide variety of studies has demonstrated that free D-aspartate and D-serine occur in the mammals and may have important functions. To gain an insight into the metabolic pathways of endogenous free D-aspartate and D-serine, we have investigated the effect of icv and systemic administration of L-serine on the concentrations of D- and L-serine in the several brain areas of infant and adult rat. Intraperitoneal administration of L-serine caused a drastic and significant increase in the levels of D- and L-serine in the cortex, diencephalon, midbrain, pons-medulla, cerebellum, liver and kidney of infant rat at 6 h after the administration. Icv injection of L-serine caused a rapid and transient increase in the L-serine levels in almost all brain regions of adult rat, with its peak at 2 h or 4 h after the injection, whereas D-serine levels rapidly increased, peaked at 6 h after the administration. These results suggest that free D-serine is formed directly by the racemization of L-serine in the brain. In contrast, because intraperitoneal and icv administration of L-aspartate failed to increase the level of D-aspartate, L-aspartate is unlikely to be a precursor of D-aspartate.