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原代星形胶质细胞中甘氨酸的代谢:肌酸、丝氨酸和谷胱甘肽的合成。

Metabolism of glycine in primary astroglial cells: synthesis of creatine, serine, and glutathione.

作者信息

Dringen R, Verleysdonk S, Hamprecht B, Willker W, Leibfritz D, Brand A

机构信息

Physiologisch-chemisches Institut der Universität, Tübingen, Germany.

出版信息

J Neurochem. 1998 Feb;70(2):835-40. doi: 10.1046/j.1471-4159.1998.70020835.x.

DOI:10.1046/j.1471-4159.1998.70020835.x
PMID:9453580
Abstract

The metabolism of [2-13C]glycine in astroglia-rich primary cultures obtained from brains of neonatal Wistar rats was investigated using 13C NMR spectroscopy. After a 24-h incubation of the cells in a medium containing glucose, glutamate, cysteine, and [2-13C]glycine, cell extracts and incubation media were analyzed for 13C-labeled compounds. Labeled creatine, serine, and glutathione were identified in the cell extracts. If arginine and methionine were present during the incubation with [2-13C]glycine, the amount of de novo synthesized [2-13C]creatine was two-fold increased, and in addition, 13C-labeled guanidinoacetate was found in cell extracts and in the media after 24 h of incubation. A major part of the [2-13C]glycine was utilized for the synthesis of glutathione in astroglial cells. 13C-labeled glutathione was found in the cell extracts as well as in the incubation medium. The presence of newly synthesized [2-13C] serine, [3-13C]serine, and [2,3-13C]serine in the cell extracts and the incubation medium proves the capability of astroglial cells to synthesize serine out of glycine and to release serine. Therefore, astroglial cells are able to utilize glycine as a precursor for the synthesis of creatine and serine. This proves that at least one cell type of the brain is able to synthesize creatine. In addition, guanidinoacetate, the intermediate of creatine synthesis, is released by astrocytes and may be used for creatine synthesis by other cells, i.e., neurons.

摘要

利用¹³C核磁共振波谱法,研究了从新生Wistar大鼠大脑中获得的富含星形胶质细胞的原代培养物中[2-¹³C]甘氨酸的代谢情况。将细胞在含有葡萄糖、谷氨酸、半胱氨酸和[2-¹³C]甘氨酸的培养基中孵育24小时后,对细胞提取物和孵育培养基中的¹³C标记化合物进行分析。在细胞提取物中鉴定出了标记的肌酸、丝氨酸和谷胱甘肽。如果在与[2-¹³C]甘氨酸孵育期间存在精氨酸和蛋氨酸,新合成的[2-¹³C]肌酸的量会增加两倍,此外,孵育24小时后,在细胞提取物和培养基中发现了¹³C标记的胍基乙酸。[2-¹³C]甘氨酸的大部分用于星形胶质细胞中谷胱甘肽的合成。在细胞提取物和孵育培养基中都发现了¹³C标记的谷胱甘肽。细胞提取物和孵育培养基中新合成的[2-¹³C]丝氨酸、[3-¹³C]丝氨酸和[2,3-¹³C]丝氨酸的存在证明了星形胶质细胞能够从甘氨酸合成丝氨酸并释放丝氨酸。因此,星形胶质细胞能够利用甘氨酸作为肌酸和丝氨酸合成的前体。这证明大脑中至少有一种细胞类型能够合成肌酸。此外,肌酸合成的中间体胍基乙酸由星形胶质细胞释放,可能被其他细胞(即神经元)用于肌酸合成。

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