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转硫途径:星形胶质细胞中谷胱甘肽半胱氨酸的来源。

The transsulfuration pathway: a source of cysteine for glutathione in astrocytes.

机构信息

UCD School of Biomolecular and Biomedical Science, Conway Institute, University College, Dublin 4, Ireland.

出版信息

Amino Acids. 2012 Jan;42(1):199-205. doi: 10.1007/s00726-011-0864-8. Epub 2011 Mar 3.

DOI:10.1007/s00726-011-0864-8
PMID:21369939
Abstract

Astrocyte cells require cysteine as a substrate for glutamate cysteine ligase (γ-glutamylcysteine synthase; EC 6.3.2.2) catalyst of the rate-limiting step of the γ-glutamylcycle leading to formation of glutathione (L: -γ-glutamyl-L: -cysteinyl-glycine; GSH). In both astrocytes and glioblastoma/astrocytoma cells, the majority of cysteine originates from reduction of cystine imported by the x (c) (-) cystine-glutamate exchanger. However, the transsulfuration pathway, which supplies cysteine from the indispensable amino acid, methionine, has recently been identified as a significant contributor to GSH synthesis in astrocytes. The purpose of this review is to evaluate the importance of the transsulfuration pathway in these cells, particularly in the context of a reserve pathway that channels methionine towards cysteine when the demand for glutathione is high, or under conditions in which the supply of cystine by the x (c) (-) exchanger may be compromised.

摘要

星形胶质细胞需要半胱氨酸作为谷氨酸半胱氨酸连接酶(γ-谷氨酰半胱氨酸合酶;EC 6.3.2.2)的底物,该酶是γ-谷氨酰循环限速步骤的催化剂,导致谷胱甘肽的形成(L:-γ-谷氨酰-L:-半胱氨酸-甘氨酸;GSH)。在星形胶质细胞和神经胶质瘤/星形细胞瘤细胞中,大部分半胱氨酸来源于通过 x(c)(-)胱氨酸-谷氨酸交换器导入的胱氨酸还原。然而,最近发现,转硫途径可以从必需氨基酸蛋氨酸供应半胱氨酸,这是星形胶质细胞中谷胱甘肽合成的重要贡献途径。本综述的目的是评估转硫途径在这些细胞中的重要性,特别是在当对谷胱甘肽的需求高时,或当 x(c)(-)交换器供应胱氨酸可能受损的情况下,该途径将蛋氨酸导向半胱氨酸的储备途径的背景下。

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