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 D-氨基酸被认为在哺乳动物中是非天然的，但大量研究表明，游离的 D-天冬氨酸和 D-丝氨酸存在于哺乳动物中，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，我们研究了静脉注射和全身给予 L-丝氨酸对婴儿和成年大鼠几个脑区中 D-和 L-丝氨酸浓度的影响。腹腔注射L-丝氨酸后6小时，幼鼠皮质、间脑、中脑、脑桥延髓、小脑、肝脏和肾脏的D-和L-丝氨酸水平急剧升高。静脉注射L-丝氨酸引起成年大鼠几乎所有脑区的L-丝氨酸水平快速短暂升高，在注射后2小时或4小时达到峰值，而D-丝氨酸水平迅速升高，在给药后6小时达到峰值。这些结果表明，游离的 D-丝氨酸是通过大脑中 L-丝氨酸的外消旋作用直接形成的。相反，由于L-天冬氨酸的腹膜内和静脉注射未能增加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。”