Alanine metabolism in the perfused rat liver -: Studies with 15N
Alanine metabolism in the perfused rat liver -: Studies with 15N
复制标题
DOI：
10.1074/jbc.m103890200
复制
发表时间：
2001-08-24
影响因子：
4.8
通讯作者：
Nissim, I
中科院分区：
文献类型：
--
作者：
Brosnan, JT;Brosnan, ME;Nissim, I
我们利用[N-15]丙氨酸或(NH3)-N-15作为代谢示踪剂，以确定肝脏灌注系统中肝脏尿素生成的氮源。在门静脉氨存在和不存在生理浓度的情况下进行了研究，以验证当NH4+：天冬氨酸比率为bbbb1时，肝蛋白水解增加提供细胞质天冬氨酸以支持尿潴留的假设。当1 mM [N-15]丙氨酸为唯一氮源时，氨基同时掺入尿素氮和谷氨酰胺氮。然而，当用1mm丙氨酸和0.3 mM NH4Cl进行研究时，丙氨酸不能以解毒所有给药氨的速度提供天冬氨酸。在这种情况下，生理浓度的氨刺激了肝脏蛋白水解。在单丙氨酸灌注时，约需要400 nmol /min/g的氮才能满足氮摄入和氮输出的平衡。当模型中加入丙氨酸和NH4Cl时，1000 nmol /min/g的氮来自肝内来源，可能是蛋白质水解。通过这种方式，内部池提供细胞质天冬氨酸，使肝脏能够处理由外部氨迅速产生的线粒体氨甲酰磷酸。这一信息可能与门静脉NH4+大大超过天冬氨酸浓度的临床情况（肾功能衰竭、肝硬化、饥饿、低蛋白饮食和恶性肿瘤）有关。在这种情况下，肝脏必须召集内部蛋白质池，以适应氨负担。
We have utilized [N-15]alanine or (NH3)-N-15 as metabolic tracers in order to identify sources of nitrogen for hepatic ureagenesis in a liver perfusion system. Studies were done in the presence and absence of physiologic concentrations of portal venous ammonia in order to test the hypothesis that, when the NH4+:aspartate ratio is >1, increased hepatic proteolysis provides cytoplasmic aspartate in order to support ureagenesis. When 1 mM [N-15]alanine was the sole nitrogen source, the amino group was incorporated into both nitrogens of urea and both nitrogens of glutamine. However, when studies were done with 1 mM alanine and 0.3 mM NH4Cl, anine failed to provide aspartate at a rate that would have detoxified all administered ammonia. Under these circumstances, the presence of ammonia at a physiologic concentration stimulated hepatic proteolysis. In perfusions with alanine alone, similar to 400 nmol of nitrogen/min/g liver was needed to satisfy the balance between nitrogen intake and nitrogen output. When the model included alanine and NH4Cl, 1000 nmol of nitrogen/min/g liver were formed from an intra-hepatic source, presumably proteolysis. In this manner, the internal pool provided the cytoplasmic aspartate that allowed the liver to dispose of mitochondrial carbamyl phosphate that was rapidly produced from external ammonia. This information may be relevant to those clinical situations (renal failure, cirrhosis, starvation, low protein diet, and malignancy) when portal venous NH4+ greatly exceeds the concentration of aspartate. Under these circumstances, the liver must summon internal pools of protein in order to accommodate the ammonia burden.