丙戊酸盐对大鼠肝细胞尿素生成的抑制作用。N-乙酰谷氨酸和乙酰辅酶A的作用。
Inhibition of ureagenesis by valproate in rat hepatocytes. Role of N-acetylglutamate and acetyl-CoA.
作者信息
Coude F X, Grimber G, Parvy P, Rabier D, Petit F
出版信息
Biochem J. 1983 Oct 15;216(1):233-6. doi: 10.1042/bj2160233.
Abstract
Valproate (0.5-5 mM) strongly inhibited urea synthesis in isolated rat hepatocytes incubated with 10 mM-alanine and 3 mM-ornithine. Valproate at the same concentrations markedly decreased concentrations of N-acetylglutamate, an essential activator of carbamoyl-phosphate synthetase I (EC 6.3.4.16), in parallel with the inhibition of urea synthesis by valproate. This compound also lowered the cellular concentration of acetyl-CoA, a substrate of N-acetylglutamate synthase (EC 2.3.1.1); glutamate, aspartate and citrulline were similarly decreased. Valproate in a dose up to 2 mM did not significantly affect the cellular concentration of ATP and had no direct effect on N-acetylglutamate synthesis, carbamoyl-phosphate synthetase I and ornithine transcarbamoylase (EC 2.1.3.3) activities.
摘要
丙戊酸盐（0.5 - 5 mM）在与10 mM丙氨酸和3 mM鸟氨酸一起孵育的离体大鼠肝细胞中强烈抑制尿素合成。相同浓度的丙戊酸盐显著降低了N - 乙酰谷氨酸的浓度，N - 乙酰谷氨酸是氨甲酰磷酸合成酶I（EC 6.3.4.16）的必需激活剂，同时丙戊酸盐抑制尿素合成。该化合物还降低了N - 乙酰谷氨酸合酶（EC 2.3.1.1）的底物乙酰辅酶A的细胞浓度；谷氨酸、天冬氨酸和瓜氨酸也同样减少。高达2 mM剂量的丙戊酸盐对细胞ATP浓度没有显著影响，并且对N - 乙酰谷氨酸合成、氨甲酰磷酸合成酶I和鸟氨酸转氨甲酰酶（EC 2.1.3.3）活性没有直接影响。
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