Marinho H S, Baptista M, Pinto R E
Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.
Biochim Biophys Acta. 1997 Apr 12;1360(2):157-68. doi: 10.1016/s0925-4439(96)00075-0.
Glutathione metabolism was studied in rat liver during diethylnitrosamine (DEN) carcinogenesis. Some studies were also made in foetal rat liver. Endogenous GSH and non-protein thiols concentrations are increased in DEN-treated rats when compared to non-treated rats but no differences were found in cysteine, total thiols and protein thiols concentration. In foetal liver GSH concentration is only 35% of that in DEN-treated rat liver. The activities of several enzymes involved in glutathione metabolism are changed in DEN-treated rats. gamma-Glutamyl transferase activity and cysteine formation from GSH by liver homogenates is increased sevenfold. gamma-Glutamylcysteine synthetase activity, initial rate of [35S]cysteine incorporation in gamma-glutamylcysteine and initial rate of GSH formation from [35S]cysteine are increased two-fold. Cytosolic GSH S-transferase activity is increased twofold in DEN-treated rats and so GSH S-conjugates concentration is probably also increased. In foetal rat liver gamma-glutamyl transferase activity is about the same but gamma-glutamylcysteine synthetase activity is only 10% of that in DEN-treated rat liver. The increased GSH concentration in DEN-treated rat liver is probably due to the simultaneous increase in the activities of gamma-glutamyl transferase and gamma-glutamylcysteine synthetase. Blood plasma total glutathione is increased 1.4 times in DEN-treated rats, but no differences are found in GSH hepatic arteriovenous gradient. This associated with the increased gamma-glutamyl transferase activity suggests that sinusoidal GSH efflux is increased in DEN-treated rats.
在二乙基亚硝胺（DEN）致癌过程中对大鼠肝脏的谷胱甘肽代谢进行了研究。还对胎鼠肝脏进行了一些研究。与未处理的大鼠相比，DEN处理的大鼠体内内源性谷胱甘肽（GSH）和非蛋白硫醇浓度增加，但半胱氨酸、总硫醇和蛋白硫醇浓度未发现差异。胎肝中GSH浓度仅为DEN处理的大鼠肝脏的35%。DEN处理的大鼠中，几种参与谷胱甘肽代谢的酶的活性发生了变化。肝脏匀浆中γ-谷氨酰转移酶活性以及由GSH生成半胱氨酸的能力增加了7倍。γ-谷氨酰半胱氨酸合成酶活性、[35S]半胱氨酸掺入γ-谷氨酰半胱氨酸的初始速率以及由[35S]半胱氨酸生成GSH的初始速率增加了两倍。DEN处理的大鼠中胞质GSH S-转移酶活性增加了两倍，因此GSH S-共轭物浓度可能也增加了。在胎鼠肝脏中，γ-谷氨酰转移酶活性大致相同，但γ-谷氨酰半胱氨酸合成酶活性仅为DEN处理的大鼠肝脏的10%。DEN处理的大鼠肝脏中GSH浓度增加可能是由于γ-谷氨酰转移酶和γ-谷氨酰半胱氨酸合成酶活性同时增加。DEN处理的大鼠血浆总谷胱甘肽增加了1.4倍，但GSH肝动静脉梯度未发现差异。这与γ-谷氨酰转移酶活性增加相关，表明DEN处理的大鼠肝血窦中GSH外流增加。
