GLUTATHIONE - INTERORGAN TRANSLOCATION, TURNOVER, AND METABOLISM
GLUTATHIONE - INTERORGAN TRANSLOCATION, TURNOVER, AND METABOLISM
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DOI：
10.1073/pnas.76.11.5606
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发表时间：
1979-01-01
影响因子：
11.1
通讯作者：
MEISTER, A
中科院分区：
文献类型：
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作者：
GRIFFITH, OW;MEISTER, A
谷氨酸被易位出细胞;具有膜结合的γ的细胞谷氨酰转肽酶可以利用易位的谷胱甘肽，而从没有明显转肽酶的细胞输出的谷胱甘肽进入血浆。通过肾脏和其他具有转肽酶的器官从血浆中去除谷胱甘肽。在这些研究中，小鼠和大鼠用丁噻鲁胺亚砜亚胺（一种γ-谷氨酰胺的选择性和有效抑制剂）处理，谷氨酰半胱氨酸合成酶和谷胱甘肽合成的研究表明，谷胱甘肽在许多组织中，特别是肾脏、肝脏和胰腺中的周转率很高;小鼠骨骼肌中的周转率约为肾脏的60%。对手术切除一个或两个肾脏并用γ-谷氨酰转肽酶抑制剂D-γ-谷氨酰基-（o-羧基）苯酰肼确定了肾外γ-谷氨酰转肽酶活性占血浆谷胱甘肽总利用量的约1/3。用转肽酶抑制剂治疗的正常动物在尿液中排出大量谷胱甘肽。它们还分泌γ-谷氨酰半胱氨酸，表明谷胱甘肽在半胱氨酰甘氨酸结合的裂解可能具有代谢意义。目前和较早的发现导致谷胱甘肽γ的代谢和易位的试验性方案（在此提出）。谷氨酰氨基酸和相关化合物。
Glutathione is translocated out of cells; cells that have membrane-bound .gamma.-glutamyl transpeptidase can utilize translocated glutathione, whereas glutathione exported from cells that do not have appreciable transpeptidase enters the blood plasma. Glutathione removed from the plasma by the kidney and other organs that have transpeptidase. Studies in which mice and rats were treated with buthionine sulfoximine, a selective and potent inhibitor of .gamma.-glutamylcysteine synthetase and of glutathione synthesis, showed that glutathione turns over at a significant rate in many tissues, especially kidney, liver and pancreas; rate of turnover in mouse skeletal muscle is about 60% of that in the kidney. Experiments on rats surgically deprived of 1 or both kidneys and treated with the .gamma.-glutamyl transpeptidase inhibitor D-.gamma.-glutamyl-(o-carboxy)phenylhydrazide established that extrarenal .gamma.-glutamyl transpeptidase activity accounted for the utilization of about 1/3 of the total blood plasma glutathione. Normal animals treated with the transpeptidase inhibitor excreted large amounts of glutathione in their urine. They also excreted .gamma.-glutamylcysteine, suggesting that cleavage of glutathione at the cysteinylglycine bound may be of metabolic significance. Present and earlier findings lead to a tentative scheme (presented here) for metabolism and translocation of glutathione, .gamma.-glutamyl amino acids and related compounds.