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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。N-乙酰谷氨酸（NAG）是排尿素动物体内尿素循环的第一个酶--线粒体氨甲酰磷酸合成酶I（CPSI）的一种重要的变构辅因子。在没有NAG的情况下，CPSI的酶活性实际上是不可检测的，因此，NAG的缺乏将导致尿素生成的阻断，其程度将取决于NAG缺乏的程度。据信线粒体内NAG的浓度控制CPSI的活性，并因此调节尿素生成。本方案的目的是研究N-氨甲酰谷氨酸盐（Carbaglu）对[15 N]氨掺入尿素的影响，作为通过DNA检测诊断为遗传性N-乙酰谷氨酸合酶缺乏症患者的尿素生成能力恢复的指标

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