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大鼠脑中N-乙酰-L-天冬氨酸的代谢

Metabolism of N-acetyl-L-aspartate in rat brain.

作者信息

Miller S L, Daikhin Y, Yudkoff M

机构信息

Division of Neurology Research, Children's Hospital of Philadelphia 19104, USA.

出版信息

Neurochem Res. 1996 May;21(5):615-8. doi: 10.1007/BF02527761.

Abstract

The abundance and developmental regulation of N-acetylaspartate (NAA) in brain suggest that it plays an important role in brain metabolism. Previous studies demonstrated that NAA transports acetate from the mitochondrion to the cytoplasm where it is utilized for lipid synthesis, however, the metabolic fate of NAA-derived aspartate is not established. To investigate NAA metabolism, rats were injected intracranially with N-([2H3]acetyl)-L-[15N]aspartate ([2H3,15N]NAA) and whole brain metabolites were analyzed using gas chromatography and mass spectrometry techniques (GC/MS). The rapid decline of [2H3,15N]NAA was associated with a rapid appearance of [15N]glutamate, indicating rapid transamination of the [15N]aspartate that was derived from the enzymatic hydrolysis of [2H3,15N]NAA. Inability to detect [15N]NAA in brain extracts in several experiments indicates that the 15N moiety is not reutilized for NAA synthesis and suggests one metabolic role of NAA may be the transport of amino nitrogen from the mitochondrion to the cytoplasm.

摘要

大脑中N-乙酰天门冬氨酸(NAA)的丰度及发育调控表明其在脑代谢中发挥重要作用。先前的研究表明,NAA将乙酸盐从线粒体转运至细胞质,在细胞质中乙酸盐用于脂质合成,然而,源自NAA的天门冬氨酸的代谢归宿尚未明确。为研究NAA代谢,给大鼠颅内注射N-([2H3]乙酰基)-L-[15N]天门冬氨酸([2H3,15N]NAA),并采用气相色谱和质谱技术(GC/MS)分析全脑代谢物。[2H3,15N]NAA的快速下降与[15N]谷氨酸的快速出现相关,这表明源自[2H3,15N]NAA酶促水解的[15N]天门冬氨酸发生了快速转氨作用。在多个实验中无法在脑提取物中检测到[15N]NAA,这表明15N部分未被重新用于NAA合成,并提示NAA的一个代谢作用可能是将氨基氮从线粒体转运至细胞质。

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