Bode A M, Nordlie R C
Department of Physiology, University of North Dakota School of Medicine, Grand Forks 58202.
J Biol Chem. 1993 Aug 5;268(22):16298-301.
L-Proline and L-glutamine were used to probe the inverse relationship between glycogenesis and ureagenesis in isolated, perfused livers from 48-h fasted rats. Both amino acids may provide nitrogen in the form of NH+4 for carbamyl-P synthesis. However, one molecule of glutamine may provide additionally for the synthesis of one molecule of the urea cycle substrate L-aspartate, but proline can provide for the synthesis of a molecule of NH+4 or one molecule of aspartate on an either/or basis only. In all perfusates, glucose was initially 30 mM (to favor phosphotransferase activity of glucose-6-phosphatase) and 0.5 mM 3-mercaptopicolinate was present (to inhibit glyconeogenesis from endogenous substrates, from the added amino acids, and via the indirect pathway). Glycogenesis from glucose, perfusate and hepatic urea formation, and levels of hepatic glucose-6-P, citrulline, PPi, and carbamyl-P were measured. The addition of glutamine to the perfusate markedly stimulated the urea cycle, but not glycogenesis. Hepatic urea level, perfusate urea concentration, and hepatic citrulline and PPi increased while carbamyl-P content decreased. In contrast, proline stimulated glycogenesis from glucose, but not ureagenesis. In the proline-supplemented compared with glutamine group, hepatic glycogenesis and carbamyl-P content increased; hepatic glucose-6-P levels showed a tendency toward increase; and hepatic urea formation, hepatic citrulline, and PPi levels were decreased. These observations are interpreted to support an hepatic mechanism whereby the relative availability of carbamyl-P to the urea cycle and as a substrate for glucose phosphorylation via phosphotransferase activity of the glucose-6-phosphatase system preliminary to glycogenesis from glucose is a major metabolic determinant.
L-脯氨酸和L-谷氨酰胺被用于探究48小时禁食大鼠分离灌注肝脏中糖原生成与尿素生成之间的反比关系。这两种氨基酸都可以以NH⁺₄的形式为氨基甲酰磷酸的合成提供氮。然而，一分子谷氨酰胺还可以额外为一分子尿素循环底物L-天冬氨酸的合成提供原料，但脯氨酸只能二者择一地为一分子NH⁺₄或一分子天冬氨酸的合成提供原料。在所有灌注液中，葡萄糖初始浓度为30 mM（以利于葡萄糖-6-磷酸酶的磷酸转移酶活性），并存在0.5 mM 3-巯基吡啶甲酸盐（以抑制内源性底物、添加的氨基酸以及通过间接途径进行的糖异生）。测定了葡萄糖的糖原生成、灌注液和肝脏尿素生成以及肝脏葡萄糖-6-磷酸、瓜氨酸、焦磷酸和氨基甲酰磷酸的水平。向灌注液中添加谷氨酰胺显著刺激了尿素循环，但对糖原生成没有影响。肝脏尿素水平、灌注液尿素浓度以及肝脏瓜氨酸和焦磷酸增加，而氨基甲酰磷酸含量降低。相比之下，脯氨酸刺激了葡萄糖的糖原生成，但对尿素生成没有影响。与谷氨酰胺组相比，在添加脯氨酸的组中，肝脏糖原生成和氨基甲酰磷酸含量增加；肝脏葡萄糖-6-磷酸水平呈增加趋势；肝脏尿素生成、肝脏瓜氨酸和焦磷酸水平降低。这些观察结果被解释为支持一种肝脏机制，即氨基甲酰磷酸作为尿素循环的原料以及通过葡萄糖-6-磷酸酶系统磷酸转移酶活性作为葡萄糖磷酸化底物在由葡萄糖进行糖原生成之前的相对可用性是一个主要的代谢决定因素。
