Anderson M E, Meister A
Proc Natl Acad Sci U S A. 1983 Feb;80(3):707-11. doi: 10.1073/pnas.80.3.707.
Administration of gamma-glutamylcystine or of gamma-glutamylcysteine disulfide to mice leads to significantly increased levels of glutathione in the kidney as compared to controls given glutamate plus cysteine (or cystinylbisglycine). Studies with gamma-glutamylcystine selectively labeled with 35S in either the internal or external S atom indicate preferential utilization of the gamma-glutamylcysteine moiety of this compound for glutathione synthesis. Mice depleted of glutathione by treatment with buthionine sulfoximine do not significantly use the disulfides gamma-glutamylcystine or gamma-glutamylcysteine disulfide but do use gamma-glutamylcysteine for glutathione synthesis. These findings suggest a pathway in which gamma-glutamylcystine, formed by transpeptidation between glutathione and cystine, is transported and reduced by transhydrogenation with glutathione to cysteine and gamma-glutamylcysteine; the latter is used directly for glutathione synthesis. The findings show transport of gamma-glutamyl amino acids, indicate an alternative pathway of glutathione synthesis, and demonstrate a means of increasing kidney glutathione levels.
与给予谷氨酸加半胱氨酸（或胱氨酰双甘氨酸）的对照组相比，给小鼠施用γ-谷氨酰胱氨酸或γ-谷氨酰半胱氨酸二硫化物会导致肾脏中谷胱甘肽水平显著升高。对内部或外部硫原子用35S选择性标记的γ-谷氨酰胱氨酸进行的研究表明，该化合物的γ-谷氨酰半胱氨酸部分优先用于谷胱甘肽合成。用丁硫氨酸亚砜胺处理使谷胱甘肽耗竭的小鼠不会显著利用二硫化物γ-谷氨酰胱氨酸或γ-谷氨酰半胱氨酸二硫化物，但会利用γ-谷氨酰半胱氨酸进行谷胱甘肽合成。这些发现提示了一条途径，即由谷胱甘肽和胱氨酸之间的转肽作用形成的γ-谷氨酰胱氨酸，通过与谷胱甘肽的转氢作用被转运并还原为半胱氨酸和γ-谷氨酰半胱氨酸；后者直接用于谷胱甘肽合成。这些发现显示了γ-谷氨酰氨基酸的转运，表明了谷胱甘肽合成的另一条途径，并证明了一种提高肾脏谷胱甘肽水平的方法。
