HEPATIC UREAGENESIS--STUDIES WITH 15-N GC-MS AND 13C NMR

这项建议需要对这些机制进行全面审查 控制肝性尿失禁和氨解毒作用 分离的肝细胞和分离的灌流肝脏。这项工作 将讨论四个主要主题：(1)确定 作为氨和尿素氮前体的各种氨基酸 代谢条件；(2)嘌呤核苷酸的作用 提供用于合成的氮气的循环 谷氨酰胺的尿素；(3)各种效应物和/或 尿失禁抑制剂在确定尿素来源中的应用 (4)氢离子浓度的影响(S)。 调节通过肝脏的氮流。后一主题将 重视肝脏氮代谢的研究 在急性或慢性酸化或碱化的大鼠身上。 这部作品的一个独特之处是使用了生理媒介 含有大多数氨基酸，通常存在于 细胞外液，其中只有一种将被标记为15N 或13C。通过利用气相色谱-质谱仪和 核磁共振定量稳定同位素富集物 在氨、尿素、氨基酸和腺核苷酸中，它将是 有可能测量代谢物流量并确定重要的 前体-产品之间的关系，这是迄今为止 不可能。DO获得的数据将具有科学意义 加深对尿失禁和肝氮素的认识 新陈代谢。慢性阻塞性肺疾病患者的合理临床管理 肝病是以这样的科学基础为前提的。

This proposal entails a comprehensive examination of the mechanisms controlling hepatic ureagenesis and ammonia detoxification in isolated hepatocytes and the isolated perfused liver. The work will address four primary themes: (1) identification of those amino acids serving as precursor to ammonia and urea N in a variety of metabolic conditions; (2) the role of the purine nucleotide cycle in furnishing the nitrogen utilized for the synthesis of either urea of glutamine; (3) the role of various effectors and/or inhibitors of ureagenesis in determining the sources of urea nitrogen; and (4) the effect(s) of hydrogen ion concentration in regulating nitrogen flux through the liver. The latter theme will receive special attention through the study of hepatic N metabolism in rats made acutely or chronically acidotic or alkalotic. A unique feature of the work is the use of physiologic medium containing most of the amino acids normally present in the extracellular fluid, only one of which will be labelled with 15N or 13C. By utilizing both gas chromatography-mass spectrometry and nuclear magnetic resonance to quantify stable isotopic enrichment in ammonia, urea, amino acids and adenine nucleotides, it will be possible to measure metabolite flux and to identify important precursor-product relationships in a manner which has been hitherto impossible. The data do obtained will be of scientific import by deepening our understanding of ureagenesis and of hepatic nitrogen metabolism. The rational clinical management of patients with liver disease presupposes such a scientific foundation.