ENTERAL PRECURSORS FOR UREA SYNTHESIS IN HUMANS

人体尿素合成的肠内前体

• 批准号: 6178166
• 负责人: PETER J. REEDS
• 金额: $ 8.16万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 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 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6178166
• 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.

本研究的目的是为了更深入地了解体内 尿素循环障碍患者的氮代谢。 最近 基于稳定同位素的正常个体尿素合成研究， 鸟氨酸转氨甲酰酶缺乏症（OTCD）的携带者， 以下假设。1：衍生自第一-第二尿素前体的尿素前体 通过肠道代谢的膳食蛋白质被利用更多 比来源于组织的前体更有效地用于尿素生成 新陈代谢. 2：因此，患有尿素受损的人 循环活动能够代谢过多的膳食蛋白质更多 比外围产生的前体更有效。 这就是 观察到压力或感染的施加与 在女性OTCD携带者中存在代谢失调， 影响OTCD男性。3：尿素与尿素的效率差异 由肠和外周来源的底物合成， 一个重要的因素，在可变的表型和情节的性质， OTCD。这些假设将通过进行稳定同位素测试来验证。 正常对照和OTCD携带者中尿素合成的研究。的 研究的具体目标如下。1：定量尿素 从饮食和系统尿素氮前体合成 膳食状态2：量化更长时期的 中等或更高的蛋白质摄入量对相对利用率的影响 内源性和膳食氮源对尿素生成的影响。 尿素产量将用[18 O]尿素测定并进行比较 同时测量[15 N]从口腔转移 15 NH 4CI或[15 N]丙氨酸（作为膳食示踪剂）或静脉注射 15 NH 4Cl、[5- 15 N]谷氨酰胺或[15 N]丙氨酸（作为内源性代谢产物的示踪剂）。 生成的前体）。这些信息将有助于了解 氮代谢的OTCD，并可能导致改善营养 通过确定患者可以接受的蛋白质摄入量范围来进行护理， 成功适应。 此外，结果将更广泛 对了解水稻生长期氮代谢和尿素生成的意义 压力和感染。