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

尽管D-氨基酸在哺乳动物中被认为是非天然的，但各种研究表明，哺乳动物中存在游离的D-天冬氨酸和D-丝氨酸，并且可能具有重要的功能。为了深入了解内源性游离D-天冬氨酸和D-丝氨酸的代谢途径，我们研究了icv和全身给药L-丝氨酸对婴儿和成年大鼠几个脑区D-和L-丝氨酸浓度的影响。腹腔注射L-丝氨酸后6 h，幼鼠皮层、间脑、中脑、脑桥-髓质、小脑、肝脏和肾脏中D-丝氨酸和L-丝氨酸的含量显著增加。脑室注射L-丝氨酸后，成年大鼠几乎所有脑区的L-丝氨酸水平均迅速升高，峰值出现在注射后2 h或4 h，而D-丝氨酸水平则迅速升高，峰值出现在注射后6 h。这些结果表明，游离D-丝氨酸是直接形成的消旋L-丝氨酸在大脑中。相反，由于腹膜内和icv给予L-天冬氨酸未能增加D-天冬氨酸的水平，因此L-天冬氨酸不太可能是D-天冬氨酸的前体。

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.