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Hum Mutat. 2005 Mar;25(3):293-8.

Late onset N-acetylglutamate synthase deficiency caused by hypomorphic alleles.

Author information

1
Children's Research Institute, Children's National Medical Center, The George Washington University, Washington, DC 20010, USA.

Abstract

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.

PMID:
15714518
DOI:
10.1002/humu.20146
[Indexed for MEDLINE]

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