ENTERAL PRECURSORS FOR UREA SYNTHESIS IN HUMANS

人体尿素合成的肠内前体

• 批准号: 6381230
• 负责人: PETER J. REEDS
• 金额: $ 15.66万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6381230
• 关键词: biosynthesis; biotransformation; clinical research; dietary proteins; heterozygote; human subject; nitrogen metabolism; nutrition related tag; ornithine carbamoyl phosphate deficiency; urea; urea cycle

The goal of the research is to achieve a deeper understanding of in vivo nitrogen metabolism in patients with urea cycle disorders. Recent stable isotope-based studies of urea synthesis in normal individuals and in carriers of ornithine transcarbamylase deficiency (OTCD) have led us to the following hypotheses. 1: Urea precursors derived from the first- pass intestinal metabolism of dietary protein are utilized more efficiently for ureagenesis than are precursors derived from tissue metabolism. 2: As a consequence, individuals who have a compromised urea cycle activity are able to metabolize excessive dietary protein more effectively than peripherally generated precursors. This underlies the observation that the imposition of stress or infection is associated with metabolic decompensation in female OTCD carriers and mildly affected OTCD males. 3: The difference in the efficiency with which urea is synthesized from substrates of intestinal and peripheral origin is an important factor in the variable phenotype and episodic nature of OTCD. These hypotheses will be tested by carrying out stable isotopic studies of urea synthesis in normal controls and OTCD carriers. The studies will have the following specific aims. 1: Quantify urea synthesis from dietary and systemic urea nitrogen precursors in the prandial state. 2: Quantify the impact of a more prolonged period of moderate or higher protein intake on the relative utilization of endogenous and dietary nitrogen sources for ureagenesis. Urea production will be determined with [18O] urea and will be compared with simultaneous measurements of the transfer of [15N] from oral 15NH4CI, or [15N] alanine (as dietary tracers) or from intravenous 15NH4CI, [5-15N] glutamine or [15N]alanine (as tracers of endogenously generated precursors). The information will enhance understanding of nitrogen metabolism in OTCD and may lead to improvements in nutritional care by establishing the range of protein intakes to which patients can successfully adapt. In addition the results will be of broader significance to understanding nitrogen metabolism and ureagenesis during stress and infection.

这项研究的目标是更深入地了解体内 尿素循环障碍患者的氮代谢。近期 基于稳定同位素的正常人和正常人尿素合成的研究 在鸟氨酸转氨酶缺乏症(OTCD)的携带者中 以下是假设。1：尿素前体来自第一个- 通过肠道蛋白质的代谢得到更多的利用 与来自组织的前体相比，尿失禁更有效 新陈代谢。他说：因此，尿素受损的人 循环活动能够更多地代谢过量的食物蛋白质 比外围生成的前体更有效。这是 观察到施加压力或感染与 女性OTCD携带者代谢失代偿和轻度 受OTCD影响的男性。3：尿素效率的差异 是由肠道和外周来源的底物合成的 多种多样的表型和情节性质的一个重要因素 OTCD。这些假说将通过进行稳定同位素来检验。 正常对照组和OTCD携带者尿素合成的研究。这个 研究将有以下具体目标。1：量化尿素 日粮和系统尿素氮前体的合成 进餐状态。2：量化更长时期的影响 适量或较高蛋白质摄入量对机体相对利用率的影响 尿失禁的内源和饮食氮源。 尿素产量将与[18O]尿素进行测定，并进行比较 同时测量[15N]从口腔的转移 15NH4CI，或[15N]丙氨酸(作为膳食示踪剂)或静脉注射 15NH4CI、[5-15N]谷氨酰胺或[15N]丙氨酸(作为内源性的示踪剂 生成的前体)。这些信息将增进对 OTCD的氮代谢，并可能导致营养状况的改善 通过确定患者可以摄取的蛋白质摄入量范围进行护理 成功适应。此外，结果将是更广泛的 认识尿失禁与氮代谢的意义 压力和感染。