Late onset N-acetylglutamate synthase deficiency caused by hypomorphic alleles
Late onset N-acetylglutamate synthase deficiency caused by hypomorphic alleles
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DOI：
10.1002/humu.20146
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发表时间：
2005-01-01
期刊：
影响因子：
3.9
通讯作者：
Tuchman, M
中科院分区：
文献类型：
--
作者：
Caldovic, L;Morizono, H;Tuchman, M
N-乙酰谷氨酸 (NAG) 是一种独特的辅助因子，对于肝脏中氨转化为尿素至关重要。 N-乙酰谷氨酸合酶 (NAGS) 催化 NAG 的形成。 NAGS 缺乏会导致尿素生成受阻，导致高氨血症。尽管已在 NAGS 基因中鉴定出许多突变，但尚未检查它们对 NAGS 酶活性的影响。我们在这里描述了两个 NAGS 缺陷家族的三种突变。对纯化的重组突变蛋白的研究揭示了对 NAGS 对底物的亲和力以及催化速率的有害影响。这些研究使人们更好地了解 NAGS 的功能，以及导致遗传性 NAGS 缺陷的突变的有害作用机制。 (C) 2005 Wiley-Liss, Inc.
N-acetylglutamate (NAG) is a unique cofactor that is essential for the conversion of ammonia to urea in the liver. N-acetylglutamate synthase (NAGS) catalyzes the formation of NAG. Deficiency of NAGS causes a block in ureagenesis resulting in hyperammonemia. Although a number of mutations have been identified in the NAGS gene, their effects on NAGS enzymatic activity have not been examined. We describe here three mutations in two families with NAGS deficiency. Studies of the purified recombinant mutant proteins revealed deleterious effects on NAGS affinity for substrates, and on the rate of catalysis. These studies provide a better understanding of the function of NAGS, and the mechanisms for deleterious effect of mutations causing inherited NAGS deficiency. (C) 2005 Wiley-Liss, Inc.