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

哺乳动物D-丝氨酸和D-天冬氨酸生物合成途径的研究

• 批准号: 09680772
• 负责人: HASHIMOTO Atsushi
• 金额: $ 1.73万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680772/
• 关键词: D-serine; D-aspartate; biosynthesis; D-アミノ酸

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.

尽管已假定D-氨基酸在哺乳动物中是不自然的，但各种各样的研究表明，哺乳动物中出现游离D-天冬氨酸和D-丝氨酸，并且可能具有重要功能。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和全身施用L-丝氨酸对婴儿和成年大鼠的几个大脑区域D-和L- serine浓度的影响。腹膜内的L塞林给药在施用后6小时，在皮质，双脑，中脑，中脑，脑海中，小脑和肾脏的皮质，脑脑，中脑，小脑和肾脏的D-和L丝氨酸的水平急剧上升和显着增加。 ICV注射L塞林导致几乎所有成年大鼠大脑区域的L丝氨酸水平迅速而瞬时增加，其峰值在注射后2小时或4小时峰值，而D丝氨酸水平迅速增加，在给药后6小时峰值。这些结果表明，游离D-丝氨酸是直接由大脑中L丝氨酸的种族化形成的。相反，由于腹膜内和ICV的L-天冬氨酸施用未能增加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。

项目成果

Hashimoto A.: "Free D-aspartate and D-serine in the mammalian brain and periphery"Pregress in Neurobiology. 52. 325-353 (1997)

Hashimoto A.：“哺乳动物大脑和外周中的游离 D-天冬氨酸和 D-丝氨酸”神经生物学进展。

Atsushi Hashimoto: "Free D-aspartate and D-serine in the mammalian brain and periphery"Progress in Neurobiology. 52. 325-353 (1997)

Atsushi Hashimoto：“哺乳动物大脑和外周中的游离 D-天冬氨酸和 D-丝氨酸”神经生物学进展。

A.Hashimoto and T.Oka: "Free D-aspartate and D-serine in the mammalian brain and periphery." Progress in Neurobiology. 52. 325-353 (1997)

A.Hashimoto 和 T.Oka：“哺乳动物大脑和外周中存在游离的 D-天冬氨酸和 D-丝氨酸。”