Morimoto B H, Brady J F, Atkinson D E
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024.
Biochem J. 1990 Dec 15;272(3):671-5. doi: 10.1042/bj2720671.
Increases in dietary protein have been reported to increase the rate of citrulline synthesis and the level of N-acetylglutamate in liver. We have confirmed this effect of diet on citrulline synthesis in rat liver mitochondria and show parallel increases in N-acetylglutamate concentration. The magnitude of the effect of arginine in the suspending medium on citrulline synthesis was also dependent on dietary protein content. Mitochondria from rats fed on a protein-free diet initially contained low levels of N-acetylglutamate, and addition of arginine increased the rate of its synthesis. Citrulline synthesis and acetylglutamate content in these mitochondria increased more than 5-fold when 1 mM-arginine was added. A diet high in protein results in mitochondria with increased N-acetylglutamate and a high rate of citrulline synthesis; 1 mM-arginine increased citrulline synthesis in such mitochondria by only 36%. The concentration of arginine in portal blood was 47 microM in rats fed on a diet lacking protein, and 182 microM in rats fed on a diet containing 60% protein, suggesting that arginine may be a regulatory signal to the liver concerning the dietary protein intake. The rates of citrulline synthesis were proportional to the mitochondrial content of acetylglutamate in mitochondria obtained from rats fed on diets containing 0, 24, or 60% protein, whether incubated in the absence or presence of arginine. Although the effector concentrations are higher than the Ka for the enzymes, these results support the view that concentrations of both arginine and acetylglutamate are important in the regulation of synthesis of citrulline and urea. Additionally, the effects of dietary protein level (and of arginine) are exerted in large part by way of modulation of the concentration of acetylglutamate.
据报道，饮食中蛋白质增加会提高瓜氨酸合成速率以及肝脏中N - 乙酰谷氨酸水平。我们已经证实了饮食对大鼠肝脏线粒体中瓜氨酸合成的这种影响，并发现N - 乙酰谷氨酸浓度也相应增加。悬浮培养基中精氨酸对瓜氨酸合成的影响程度也取决于饮食中的蛋白质含量。以无蛋白饮食喂养的大鼠的线粒体最初含有低水平的N - 乙酰谷氨酸，添加精氨酸会提高其合成速率。当添加1 mM精氨酸时，这些线粒体中的瓜氨酸合成和乙酰谷氨酸含量增加了5倍多。高蛋白饮食会导致线粒体中N - 乙酰谷氨酸增加以及瓜氨酸合成速率提高；1 mM精氨酸在此类线粒体中仅使瓜氨酸合成增加36%。缺乏蛋白质饮食的大鼠门静脉血中精氨酸浓度为47 microM，而含60%蛋白质饮食的大鼠门静脉血中精氨酸浓度为182 microM，这表明精氨酸可能是向肝脏传递有关饮食蛋白质摄入量的调节信号。无论在有无精氨酸的情况下孵育，从喂食含0%、24%或60%蛋白质饮食的大鼠获得的线粒体中，瓜氨酸合成速率与线粒体中乙酰谷氨酸含量成正比。尽管效应物浓度高于酶的解离常数（Ka），但这些结果支持这样一种观点，即精氨酸和乙酰谷氨酸的浓度在瓜氨酸和尿素合成的调节中都很重要。此外，饮食蛋白质水平（以及精氨酸）的影响在很大程度上是通过调节乙酰谷氨酸浓度来实现的。
