Intracellular cysteine and glutathione delivery systems.
Intracellular cysteine and glutathione delivery systems.
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细胞内半胱氨酸和谷胱甘肽递送系统。
DOI：
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发表时间：
1986
影响因子：
3.5
通讯作者：
O. Hwang
中科院分区：
文献类型：
--
作者：
A. Meister;M. Anderson;O. Hwang
谷氨酸在催化、代谢、运输和还原过程中发挥作用，并通过破坏自由基、活性氧中间体和内源性和外源性的其他有毒化合物来保护细胞。它也作为半胱氨酸的储存和运输形式发挥作用。谷胱甘肽的消耗（通过抑制其合成有效地完成）增加对辐射和某些有毒化合物的敏感性，并且在可以实现细胞选择性的情况下与放射疗法或化学疗法组合是有价值的。细胞内谷胱甘肽水平的增加可以保护细胞免受辐射和某些有毒化合物的侵害。通过给予半胱氨酸或谷胱甘肽可以增加谷氨酰胺水平，但这些方法并不完全令人满意。细胞谷胱甘肽水平可以通过提供γ-谷氨酰半胱氨酸合成酶或谷胱甘肽合成酶的底物来增加。L-2-氧代噻唑烷-4-羧酸盐被很好地转运到许多细胞中，并被5-氧代脯氨酸酶转化为半胱氨酸，半胱氨酸是γ-谷氨酰半胱氨酸合成酶的底物。γ-谷氨酰半胱氨酸和相关化合物被有效转运，特别是转运到肾细胞中，从而为谷胱甘肽合成酶提供底物;由于谷胱甘肽不显著抑制该酶，因此可以获得高于正常水平的谷胱甘肽，而γ-谷氨酰半胱氨酸合成酶是反馈抑制的。谷胱甘肽的衍生物被有效地运输到细胞中（谷胱甘肽本身不是）提供了另一种增加谷胱甘肽水平的方法。谷胱甘肽的单乙酯（其中甘氨酸羧基被酯化）在体内被很好地转运到肝脏和肾脏以及培养的成纤维细胞和淋巴细胞中。通过这种方法可以获得比平常高得多的谷氨酸水平，这可以保护淋巴细胞免受辐射的致命影响，保护小鼠免受对乙酰氨基酚的影响，因此这可能是一种相对安全的方法来增加细胞对辐射和某些有毒化合物的抵抗力。
Glutathione functions in catalysis, metabolism, transport, and reductive processes and in protection of cells by destruction of free radicals, reactive oxygen intermediates, and other toxic compounds of endogenous and exogenous origin. It also functions as a storage and transport form of cysteine. Depletion of glutathione (effectively accomplished by inhibition of its synthesis) increases sensitivity to radiation and to certain toxic compounds and is of value in combination with radiation therapy or chemotherapy in situations in which cell selectivity can be achieved. Increased cellular levels of glutathione protect cells against radiation and certain toxic compounds. Glutathione levels can be increased by administration of cysteine or of glutathione, but these approaches are not entirely satisfactory. Cellular glutathione levels can be increased by supplying substrate for gamma-glutamylcysteine synthetase or for glutathione synthetase. L-2-Oxothiazolidine-4-carboxylate is well transported into many cells and is converted by 5-oxoprolinase to cysteine, a substrate of gamma-glutamylcysteine synthetase. gamma-Glutamylcysteine and related compounds are effectively transported, especially into renal cells, thus providing substrate for glutathione synthetase; higher than normal levels of glutathione can be achieved because this enzyme is not significantly inhibited by glutathione, whereas gamma-glutamylcysteine synthetase is feedback-inhibited. Derivatives of glutathione that are effectively transported into cells (glutathione itself is not) offer another means of increasing glutathione levels. The monoethyl ester of glutathione (in which the glycine carboxyl group is esterified) is well transported in vivo into liver and kidney and into cultured fibroblasts and lymphoid cells. Glutathione levels much higher than usual can be obtained by this procedure, which protects lymphoid cells against the lethal effects of irradiation and mice against acetaminophen, and which therefore may be a relatively safe way to increase cellular resistance to radiation and certain toxic compounds.
DOI：
10.1016/s0021-9258(19)68270-0
发表时间：
1982-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Arthur J. L. Cooper;M. T. Haber;A. Meister
通讯作者：
Arthur J. L. Cooper;M. T. Haber;A. Meister