丙戊酸盐所致肾源性高氨血症。丙戊酸盐对大鼠肾线粒体谷氨酰胺转运的影响。

Valproate-induced hyperammonemia of renal origin. Effects of valproate on glutamine transport in rat kidney mitochondria.

作者信息

Rumbach L, Cremel G, Marescaux C, Warter J M, Waksman A

机构信息

Clinique Neurologique, Hôpital Central, France.

出版信息

Biochem Pharmacol. 1989 Nov 15;38(22):3963-7. doi: 10.1016/0006-2952(89)90675-8.

DOI:10.1016/0006-2952(89)90675-8

PMID:2512930

Abstract

The antiepileptic sodium valproate (VPA) systematically induces an asymptomatic hyperammonemia of renal origin in fasting normal human volunteers and in fasting rats, accompanied by an increased renal glutamine uptake. Fasting rats were injected with VPA and their mitochondria isolated, or isolated mitochondria of fasting rats were incubated with VPA. Transmembranal mitochondrial glutamine uptake and activities for five mitochondrial and three cytosolic enzymes involved in ammoniagenesis were measured. In VPA-incubated mitochondria, glutamine transport increased for VPA concentrations between 10(-3) and 10(-5) M; enzyme activities did not change. In mitochondria of VPA-treated rats, Km and Vmax were unaffected. These findings reflect membrane effects of VPA observed in other experimental settings.

摘要

抗癫痫药物丙戊酸钠（VPA）在禁食的正常人类志愿者和禁食大鼠中可系统性地诱发源自肾脏的无症状性高氨血症，并伴有肾脏谷氨酰胺摄取增加。给禁食大鼠注射VPA后分离其线粒体，或将禁食大鼠的分离线粒体与VPA一起孵育。测定跨膜线粒体谷氨酰胺摄取以及参与氨生成的五种线粒体酶和三种胞质酶的活性。在与VPA孵育的线粒体中，当VPA浓度在10⁻³至10⁻⁵ M之间时，谷氨酰胺转运增加；酶活性未改变。在VPA处理的大鼠的线粒体中，米氏常数（Km）和最大反应速度（Vmax）未受影响。这些发现反映了在其他实验环境中观察到的VPA的膜效应。