Molecular Characterization of Carbamoyl-Phosphate Synthetase (CPS1) Deficiency Using Human Recombinant CPS1 as a Key Tool

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Molecular 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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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 ...

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Ammonia-lowering activities and carbamoyl phosphate synthetase 1 (Cps1) induction mechanism of a natural flavonoid

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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Two novel mutations in the CPS1 gene of a newborn with carbamoyl phosphate synthetase 1 deficiency identified by next-generation sequencing

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...

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Neonatal-onset carbamoyl phosphate synthetase I deficiency

RATIONALE The carbamoyl phosphate synthetase I deficiency (CPS1D) was rare and hard to diagnose due to its atypical symptoms. Brain magnetic resonance imaging (MRI) was typically unavailable in other reports because most patients died before diagnosis was confirmed. Furthermore, it was found a new mutation that had not been described previously. PATIENT CONCERNS This is a case of neonatal-ons...

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ژورنال

عنوان ژورنال: Human Mutation

سال: 2013

ISSN: 1059-7794

DOI: 10.1002/humu.22349