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谷氨酸:它从何而来,又去向何方?

Glutamate: Where does it come from and where does it go?

作者信息

Olsen Grethe M, Sonnewald Ursula

机构信息

Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

出版信息

Neurochem Int. 2015 Sep;88:47-52. doi: 10.1016/j.neuint.2014.11.006. Epub 2014 Nov 20.

Abstract

Pyruvate carboxylation, the anaplerotic reaction in the brain, has been demonstrated in astrocytes but not neurons. Since anaplerosis cannot proceed without cataplerosis in a closed system such as the brain, there have to be mechanisms to degrade molecules such as glutamate, glutamine, GABA and aspartate which have more carbon atoms than pyruvate. Pyruvate recycling is a cataplerotic process which is very active in liver. It has also been demonstrated in the brain and has been shown to proceed both in astrocytes and neurons. Increasing recycling as a consequence of increasing glutamate concentration in medium has been shown in astrocytes. In the present study cerebellar granule neurons were incubated with medium containing 0.1, 0.25 or 0.5 mM [U-(13)C]glutamate or [U-(13)C]aspartate and pyruvate recycling in combination with tricarboxylic acid (TCA) cycle metabolism was analysed in glutamate, aspartate and malate using mass spectrometry. It could be shown that pyruvate recycling of TCA cycle intermediates as seen in glutamate increased with increasing [U-(13)C]glutamate but not [U-(13)C]aspartate concentration confirming compartmentation of glutamate metabolism and the importance of glutamate in cataplerosis. Partial pyruvate recycling (lactate production from the TCA cycle) was more active in astrocytes than neurons in line with the astrocytes' greater capacity for glutamate uptake.

摘要

丙酮酸羧化作用是大脑中的回补反应,已在星形胶质细胞中得到证实,但在神经元中未得到证实。由于在大脑这样的封闭系统中,没有物质外流就无法进行物质回补,因此必须存在降解谷氨酸、谷氨酰胺、γ-氨基丁酸和天冬氨酸等比丙酮酸碳原子更多的分子的机制。丙酮酸循环是一种在肝脏中非常活跃的物质外流过程。它在大脑中也已得到证实,并且已表明在星形胶质细胞和神经元中均可进行。在星形胶质细胞中已显示,随着培养基中谷氨酸浓度的增加,循环会增强。在本研究中,将小脑颗粒神经元与含有0.1、0.25或0.5 mM [U-(13)C]谷氨酸或[U-(13)C]天冬氨酸的培养基一起孵育,并使用质谱法分析了谷氨酸、天冬氨酸和苹果酸中与三羧酸(TCA)循环代谢相结合的丙酮酸循环。结果表明,如在谷氨酸中所见,TCA循环中间体的丙酮酸循环随着[U-(13)C]谷氨酸浓度的增加而增加,但不随[U-(13)C]天冬氨酸浓度增加,这证实了谷氨酸代谢的区室化以及谷氨酸在物质外流中的重要性。部分丙酮酸循环(TCA循环产生乳酸)在星形胶质细胞中比在神经元中更活跃,这与星形胶质细胞更大的谷氨酸摄取能力一致。

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