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蛋氨酸对离体大鼠肝细胞谷胱甘肽外排的抑制作用。

Inhibition of glutathione efflux from isolated rat hepatocytes by methionine.

作者信息

Aw T Y, Ookhtens M, Kaplowitz N

出版信息

J Biol Chem. 1984 Aug 10;259(15):9355-8.

PMID:6746650
Abstract

A substantial inhibition (50-70%) of GSH efflux by methionine was demonstrated in hepatocytes isolated from fed rats. Concurrent measurements of intracellular GSH revealed maintenance of a higher concentration in methionine-supplemented cells over the 1-h incubation. Analysis of total GSH suggested that maintenance of higher intracellular GSH by methionine could be quantitatively accounted for by inhibition of GSH efflux rather than by net GSH synthesis. This conclusion was supported by studies with propargylglycine, a potent inhibitor of cysteine synthesis from methionine. Identical results were obtained in incubations containing either propargylglycine and methionine or methionine alone, thereby suggesting that net synthesis of GSH from methionine was minimal under the assay conditions. Similar decreases (40-60%) in the rate of extracellular accumulation of GSH were observed with ethionine and buthionine, two higher homologs of methionine, but not with a wide range of other naturally occurring and synthetic amino acids. The inhibition of GSH efflux by methionine was not dependent on the presence of sodium in the medium and did not correlate with metabolic consumption of ATP.

摘要

在从喂食大鼠分离出的肝细胞中,蛋氨酸对谷胱甘肽(GSH)外流有显著抑制作用(50 - 70%)。同时测定细胞内GSH发现,在1小时的孵育过程中,补充蛋氨酸的细胞内GSH浓度维持在较高水平。对总GSH的分析表明,蛋氨酸维持较高细胞内GSH水平在数量上可归因于对GSH外流的抑制,而非GSH的净合成。用炔丙基甘氨酸(一种从蛋氨酸合成半胱氨酸的有效抑制剂)进行的研究支持了这一结论。在含有炔丙基甘氨酸和蛋氨酸或仅含蛋氨酸的孵育实验中获得了相同的结果,从而表明在测定条件下,蛋氨酸净合成GSH的量极少。用乙硫氨酸和丁硫氨酸(蛋氨酸的两种高级同系物)观察到GSH细胞外积累速率有类似的降低(40 - 60%),但用多种其他天然存在的和合成的氨基酸则未观察到这种情况。蛋氨酸对GSH外流的抑制不依赖于培养基中钠的存在,也与ATP的代谢消耗无关。

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