INHIBITION OF GLUTATHIONE DISULFIDE REDUCTASE BY GLUTATHIONE
INHIBITION OF GLUTATHIONE DISULFIDE REDUCTASE BY GLUTATHIONE
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DOI：
10.1016/0003-9861(91)90163-d
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发表时间：
1991-07-01
影响因子：
3.9
通讯作者：
GILBERT, HF
中科院分区：
文献类型：
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作者：
CHUNG, PM;CAPPEL, RE;GILBERT, HF
大鼠肝脏谷胱甘肽二硫还原酶显着抑制生理浓度的产品，谷胱甘肽。GSH是GSSG的非竞争性抑制剂，在固定底物的饱和浓度下是NADPH的非竞争性抑制剂。在这两种情况下，GSH的抑制是抛物线，与2当量的要求一致。还原反应中的GSH。生理水平的产物GSH对GSSG还原的抑制将导致比在不存在抑制的情况下实现的显著更氧化的细胞内环境。考虑到细胞内高浓度GSH的抑制作用，在大鼠肝脏中维持300 nmol/min/g的基础谷胱甘肽过氧化物酶通量所需的GSSG稳态浓度估计为8-9 μm，比根据谷胱甘肽还原酶平衡常数预测的GSSG浓度高约1000倍。谷胱甘肽还原酶的动力学特性也为细胞暴露于氧化应激时观察到的谷胱甘肽（GSSG）外排增加提供了依据。由此产生的细胞内GSH的减少解除谷胱甘肽还原酶的非竞争性抑制，并导致GSSG的容量（Vmax）增加和Km降低。
Rat-liver glutathione disulfide reductase is significantly inhibited by physiological concentrations of the product, glutathione. GSH is a noncompetitive inhibitor against GSSG and an uncompetitive inhibitor against NADPH at saturating concentrations of the fixed substrate. In both cases, the inhibition by GSH is parabolic, consistent with the requirement for 2 eq. of GSH in the reverse reaction. The inhibition of GSSG reduction by physiological levels of the product, GSH, would result in a significantly more oxidizing intracellular environment than would be realized in the absence of inhibition. Considering inhibition by the high intracellular concentration of GSH, the steady-state concentration of GSSG required to maintain a basal glutathione peroxidase flux of 300 nmol/min/g in rat liver is estimated at 8–9 μm, about 1000-fold higher than the concentration of GSSG predicted from the equilibrium constant for glutathione reductase. The kinetic properties of glutathione reductase also provide a rationale for the increased glutathione (GSSG) efflux observed when cells are exposed to oxidative stress. The resulting decrease in intracellular GSH relieves the noncompetitive inhibition of glutathione reductase and results in an increased capacity (Vmax) and decreasedKmfor GSSG.