Häberle Johannes
a University Children's Hospital, Division of Metabolism, Children's Research Center, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
Expert Rev Endocrinol Metab. 2012 May;7(3):263-271. doi: 10.1586/eem.12.17.
Carglumic acid is a structural analog and the first registered synthetic form of the naturally occurring allosteric activator of the urea cycle, N-acetylglutamate (NAG), which is the product of the enzyme NAG synthase (NAGS). Because NAG is essential for the function of carbamoylphosphate synthetase 1 as the first step of the urea cycle, a decreased availability of NAG due to primary or secondary defects of NAGS will affect ammonia detoxification in the urea cycle. Carglumic acid (Carbaglu®, Orphan Europe SARL, Paris, France) is approved for the acute and long-term treatment of primary defects of NAGS in Europe and the USA. In addition, it is approved in Europe for the treatment of acute hyperammonemia in patients with specific organic acidurias that can lead to NAG deficiency secondary to inhibition of NAGS. This article reviews the use of carglumic acid for both approved indications and considers the potential of this compound for acute hyperammonemias in general.
卡谷氨酸是天然存在的尿素循环变构激活剂N - 乙酰谷氨酸（NAG）的结构类似物，也是其首个注册的合成形式，NAG是NAG合酶（NAGS）的产物。由于NAG作为尿素循环第一步中氨甲酰磷酸合成酶1功能所必需，NAGS原发性或继发性缺陷导致NAG可用性降低会影响尿素循环中的氨解毒。卡谷氨酸（Carbaglu®，欧洲孤儿药公司，法国巴黎）在欧洲和美国被批准用于NAGS原发性缺陷的急性和长期治疗。此外，在欧洲它被批准用于治疗特定有机酸尿症患者的急性高氨血症，这些有机酸尿症可因NAGS受抑制导致继发性NAG缺乏。本文综述了卡谷氨酸在上述已批准适应症中的应用，并探讨了该化合物在一般急性高氨血症治疗中的潜力。
