THE INHIBITION OF GAMMA-GLUTAMYL-TRANSFERASE TRANSPEPTIDASE AND GLUTATHIONE METABOLISM OF ISOLATED RAT-KIDNEY CELLS BY L-(ALPHA-S,5S)-ALPHA-AMINO-3-CHLORO-4, 5-DIHYDRO-5-ISOXAZOLEACETIC ACID (AT-125, NSC-163501)
THE INHIBITION OF GAMMA-GLUTAMYL-TRANSFERASE TRANSPEPTIDASE AND GLUTATHIONE METABOLISM OF ISOLATED RAT-KIDNEY CELLS BY L-(ALPHA-S,5S)-ALPHA-AMINO-3-CHLORO-4, 5-DIHYDRO-5-ISOXAZOLEACETIC ACID (AT-125, NSC-163501)
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DOI：
10.1016/0006-291x(80)90557-4
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发表时间：
1980-01-01
影响因子：
3.1
通讯作者：
MECK, RA
中科院分区：
文献类型：
--
作者：
REED, DJ;ELLIS, WW;MECK, RA
本文研究了新分离的[大鼠]肾细胞在有或无γ-谷氨酰转肽酶抑制剂L-(.alpha.S，5S)-.alpha.-amino-3-chloro-4，5-dihydro-5-isoxazoleacetic酸(AT-125)存在的情况下，细胞外谷胱甘肽、谷胱甘肽、半胱氨酸和谷胱甘肽混合二硫化物(Cys-GLY)2代谢为半胱氨酸和半胱氨酸的情况。γ-谷氨酰转肽酶的不可逆失活迅速发生，阻止了肾细胞将GSH转化为GSSG和从GSH、GSSG和CYSSG中去除γ-谷氨酰基。AT-125不影响半胱氨酰甘氨酸快速转化为半胱氨酸，说明AT-125对半胱氨酸甘氨酸二肽酶活性没有影响。GSH和GSSG的降解中间产物有很大的不同，这表明在GSH过程中可能会发生重要的硫醇二硫化物交换反应，而不是GSSG在肾细胞中的降解。
Metabolism of extracellular GSH, GSSG, the mixed disulfide of cysteine and GSH (CYSSG) and cystinyl-bis-glycine (CYS-GLY)2 to cysteine and cystine by freshly isolated [rat] kidney cells was examined with and without the presence of a potent .gamma.-glutamyl transpeptidase inhibitor, L-(.alpha.S,5S)-.alpha.-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125). Irreversible inactivation of .gamma.-glutamyl transpeptidase occurred rapidly which prevented the conversion of GSH to GSSG and removal of .gamma.-glutamyl moieties from GSH, GSSG and CYSSG by kidney cells. The rapid conversion of cystinyl-bis-glycine to cystine was not affected by AT-125 indicating that this agent had no effect upon cysteinylglycine dipeptidase activity. GSH and GSSG degradation intermediates were sufficiently different to suggest that important thiol disulfide interchange reactions may occur during GSH but not GSSG degradation by kidney cells.