Understanding carbamoyl phosphate synthetase (CPS1) deficiency by using the recombinantly purified human enzyme: Effects of CPS1 mutations that concentrate in a central domain of unknown function
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Understanding carbamoyl phosphate synthetase (CPS1) deficiency by using the recombinantly purified human enzyme: effects of CPS1 mutations that concentrate in a central domain of unknown function.
Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is an inborn error of the urea cycle that is due to mutations in the CPS1 gene. In the first large repertory of mutations found in CPS1D, a small CPS1 domain of unknown function (called the UFSD) was found to host missense changes with high frequency, despite the fact that this domain does not host substrate-binding or catalytic machinery. We ...
متن کاملMolecular characterization of carbamoyl-phosphate synthetase (CPS1) deficiency using human recombinant CPS1 as a key tool.
The urea cycle disease carbamoyl-phosphate synthetase deficiency (CPS1D) has been associated with many mutations in the CPS1 gene [Häberle et al., 2011. Hum Mutat 32:579-589]. The disease-causing potential of most of these mutations is unclear. To test the mutations effects, we have developed a system for recombinant expression, mutagenesis, and purification of human carbamoyl-phosphate synthet...
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OBJECTIVE Ammonia detoxification is essential for physiological well-being, and the urea cycle in liver plays a predominant role in ammonia disposal. Nobiletin (NOB), a natural dietary flavonoid, is known to exhibit various physiological efficacies. In the current study, we investigated a potential role of NOB in ammonia control and the underlying cellular mechanism. MATERIALS/METHODS C57BL/6...
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Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive hereditary disease which usually presents as lethal hyperammonemia. Here we report the case of a newborn infant with lethal hyperammonemia. Blood liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed increased concentrations of alanine, glutamine and histidine. Urine gas chromatography-mass spe...
متن کاملStructure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis
Human carbamoyl phosphate synthetase (CPS1), a 1500-residue multidomain enzyme, catalyzes the first step of ammonia detoxification to urea requiring N-acetyl-L-glutamate (NAG) as essential activator to prevent ammonia/amino acids depletion. Here we present the crystal structures of CPS1 in the absence and in the presence of NAG, clarifying the on/off-switching of the urea cycle by NAG. By bindi...
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ژورنال
عنوان ژورنال: Molecular Genetics and Metabolism
سال: 2014
ISSN: 1096-7192
DOI: 10.1016/j.ymgme.2014.04.003