N-CARAMYLGLUTAMATE (CARBAGLU): EFFECT ON UREAGENESIS IN N-ACETYLGLUTAMATE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。N-乙酰谷氨酸(NAG)是尿路动物体内尿素循环的第一个酶--线粒体氨基甲酰磷酸合成酶I(CPSI)的重要变构辅因子。如果没有NAG，CPSI的酶活性几乎是检测不到的，因此，NAG缺乏会导致尿失禁，其程度取决于NAG缺乏的程度。据认为，线粒体内NAG的浓度控制CPSI的活性，从而调节尿失禁。本方案的目的是研究N-氨甲酰谷氨酸甲酯(Carbaglu)对尿素中[15N]氨结合的影响，以此作为DNA检测诊断的遗传性N-乙酰谷氨酸合成酶缺乏症患者尿失禁能力恢复的指标

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. N-acetylglutamate (NAG) is an essential allosteric cofactor of mitochondrial carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle in ureotelic animals. Without NAG, the enzymatic activity of CPSI is virtually undetectable and thus, the deficiency of NAG would cause a block in ureagenesis, the degree of which would depend on the degree of NAG deficiency. It is believed that the concentrations of NAG within the mitochondria control the activity of CPSI and as such regulate ureagenesis. The purpose of this protocol is to study the effect of N-Carbamylglutamate (Carbaglu) on the incorporation of [15N]ammonia into urea as a measure of restoration of ureagenesis capacity in patients with inherited N-acetylglutamate synthase deficiency diagnosed by DNA testing