期刊
MOLECULAR GENETICS AND METABOLISM
卷 93, 期 2, 页码 172-178出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2007.09.016
关键词
arginase; arginine; ornithine; guanidino compounds; ammonia
资金
- NICHD NIH HHS [HD 06576, HD 04215] Funding Source: Medline
In humans, arginase I (AI)-deficiency results in hyperargininemia, a metabolic disorder with symptoms of progressive neurological and intellectual impairment, spasticity, persistent growth retardation, and episodic hyperammonemia. A deficiency of arginase 11 (All) has never been detected and the clinical disorder, if any, associated with its deficiency has not been defined. Since the spasticity and paucity of hyperammonemic crises seen in human Al-deficient patients are not features of the other urea cycle disorders, the likelihood of ammonia as the main neuropathogenic agent becomes extremely low, and the modest elevations of arginine seen in the brains of our mouse model of hyperargininernia make it an unlikely candidate as well. Specific guanidino compounds, direct or indirect metabolites of arginine, are elevated in the blood of patients with uremia. Other guanidino compounds are also increased in plasma and cerebrospinal fluid of hyperargininemic patients making them plausible as neurotoxins in these disorders. We analyzed several guanidino compounds in our arginase single and double knockout animals and found that a-keto-6-guanidinovaleric acid, alpha-N-acetylarginine, and argininic acid were increased in the brain tissue from the AI knockout and double knockout animals. Several compounds were also increased in the plasma, liver, and kidneys. This is the first time that several of the guanidino compounds have been shown to be elevated in the brain tissue of an arginase-deficient mammal, and it further supports their possible role as the neuropathogenic agents responsible for the complications seen in arginase deficiency. (C) 2007 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据