Glucagon stimulation of citrulline formation in isolated hepatic mitochondria.
Glucagon stimulation of citrulline formation in isolated hepatic mitochondria.
复制标题
胰高血糖素刺激离体肝线粒体中瓜氨酸的形成。
DOI：
10.1016/0003-9861(77)90166-7
复制
发表时间：
1977
影响因子：
3.9
通讯作者：
G. Graetz
中科院分区：
文献类型：
--
作者：
Russell K Yamazaki;G. Graetz
研究发现，大鼠急性胰高血糖素治疗可通过与鸟氨酸、铵离子、碳酸氢盐、磷酸盐和能量来源（如琥珀酸盐）孵育的分离肝线粒体刺激瓜氨酸的形成。通过在孵育培养基中加入[14C]碳酸氢盐监测瓜氨酸形成。通过线粒体内酶、氨甲酰磷酸合酶I和鸟氨酸转氨甲酰酶的联合作用，放射性标记被掺入瓜氨酸的脲基。通过产物色谱法证实瓜氨酸的产生。激素处理后，当线粒体内ATP通过底物氧化产生时，分离的线粒体中瓜氨酸形成的速率受到刺激。然而，当在寡霉素和解偶联剂存在的情况下使用外源性ATP时，未观察到瓜氨酸形成的激素刺激。这表明瓜氨酸形成的刺激是先前显示的完整动物胰高血糖素处理后分离的肝线粒体中存在的氧化磷酸化刺激的结果。胰高血糖素治疗刺激线粒体内ATP形成的速率，从而刺激尿素生成的初始步骤。在相同条件下，肝线粒体内的丙酮酸羧化也受到刺激。作为推论，这意味着线粒体内瓜氨酸形成和丙酮酸羧化的过程在一定程度上受氧化磷酸化速率的控制。
Acute glucagon treatment of rats has been found to stimulate the formation of citrulline by isolated hepatic mitochondria incubated with ornithine, ammonium ion, bicarbonate, phosphate, and an energy source such as succinate. Citrulline formation was monitored by inclusion of [14C]bicarbonate in the incubation medium. Through the combined actions of the intramitochondrial enzymes, carbamyl phosphate synthase I and ornithine transcarbamylase, the radioactive label is incorporated into the ureido group of citrulline. The citrulline production was confirmed by chromatography of the products. Rates of citrulline formation in the isolated mitochondria were stimulated after the hormonal treatments when intramitochondrial ATP was generated via substrate oxidation. However, when exogenous ATP was utilized in the presence of oligomycin and an uncoupler, no hormonal stimulation of citrulline formation was noted. It is suggested that the stimulation of citrulline formation is a result of the stimulation of oxidative phosphorylation previously shown to be present in isolated hepatic mitochondria after glucagon treatment of the intact animal. Glucagon treatment stimulates the rate of ATP formation within the mitochondria, thereby stimulating the initial steps of ureogenesis. Pyruvate carboxylation within hepatic mitochondria is also stimulated under the same conditions. As a corollary, it is implied that the processes of citrulline formation and pyruvate carboxylation within the mitochondria are controlled to some extent by the rate of oxidative phosphorylation.