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

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.