NITROGEN FLUX AND UREAGENESIS IN UREA CYCLE DISORDERS

尿素循环障碍中的氮通量和尿生成

• 批准号: 7605833
• 负责人: Brendan Lee
• 金额: $ 5.04万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605833
• 关键词: Affect; Amides; Amino Acids; Ammonia; Arginine; Argininosuccinate lyase deficiency; Citrullinemia; Computer Retrieval of Information on Scientific Projects Database; Condition; Defect; Disease; Family history of; Family member; Female; Funding; Gene Mutation; Genotype; Glutamine; Grant; Hyperargininemia; Infusion procedures; Institution; Intake; Measurement; Measures; Metabolic; Mitochondria; Mitochondrial Diseases; Mutation Analysis; Nitrogen; Parents; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Plasma; Production; Protein-Restricted Diet; Proteins; Rate; Research; Research Personnel; Resources; Risk; Severities; Source; United States National Institutes of Health; Urea; Urine; indexing; male; orotic aciduria; size; urea cycle

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. Normal subjects and members of families with urea cycle disorders including hemizygous OTC deficient males (mild and severe), heterozygous OTC deficient females, affected patients with autosomal recessive urea cycle defects (citrullinemia, argininosuccinic aciduria, argininemia), their unaffected parents, and their sibs will be studied in the CRC to evaluate conversion of [15N-amide]glutamine to [15N]urea. This will be compared to total urea production measured with infusion of [18O][13C]urea. Selected subjects will be studied twice under identical conditions to determine the variability of the measurements. Metabolic conversion will be correlated with the genotype and phenotype. B. Subjects will be studied under conditions of increased and decreased nitrogen intake to assess the effects of protein load and the size of the labile nitrogen pool on the measurement of flux from glutamine to urea. Normal subjects will also be studied with and without administration of arginine and alternative pathway drugs. C. Urea cycle patients, both symptomatic and asymptomatic, will be evaluated by nitrogen flux and their index of urea cycle activity defined by proportion transfer of 15N from glutamine to urea ([15N]urea/[15N]glutamine)will be correlated with phenotypic severity. At-risk urea cycle patients defined by combinations of either 1) family history, 2) plasma ammonia and amino acids, 3) urine orotic aciduria, 4) enzymatic analysis, and/or 5) DNA mutation analysis will be studied to determine whether their 15N index correlates with these other measures of phenotypic severity. Finally, subjects with molecularly or biochemically defined mitochondrial disorders will be studied for their baseline rates of ureagenesis on a low protein diet to determine whether mitochondrial abnormalities affect ureagenesis.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 A. Normal subjects and members of families with urea cycle disorders including hemizygous OTC deficient males (mild and severe), heterozygous OTC deficient females, affected patients with autosomal recessive urea cycle defects (citrullinemia, argininosuccinic aciduria, argininemia), their unaffected parents, and their sibs will be studied in the CRC to evaluate conversion of [15n-酰胺]谷氨酰胺至[15n]尿素。 这将与输注[18O] [13C]尿素的总尿素产量进行比较。 在相同条件下，将对选定的受试者进行两次研究，以确定测量值的可变性。 代谢转化率将与基因型和表型相关。 B.将在氮摄入量增加和减少的条件下研究受试者，以评估蛋白质负荷的影响以及不稳定的氮池对从谷氨酰胺到尿素的通量测量的含量。 还将在没有精氨酸和替代途径药物的情况下研究正常受试者。 尿素周期患者的症状性和无症状患者将通过氮气及其尿素周期活性指数进行评估，其尿素循环活性通过15n从谷氨酰胺到尿素的比例转移（[15N]尿素/[15n]谷氨酰胺）将与表型严重程度相关。 在1）家族史，2）血浆氨氨和氨基酸的结合定义的高风险尿素周期患者，3）尿酸酸性酸性，4）酶学分析和/或5）将研究DNA突变分析以确定其15N指数是否与这些其他表型严重程度的其他指标相关。 最后，将研究患有分子或生化定义的线粒体疾病的受试者，以低蛋白质饮食的基线尿素发生率进行研究，以确定线粒体异常是否会影响尿素发生。