WordNet

a salt of phosphoric acid (同)orthophosphate, inorganic_phosphate
carbonated drink with fruit syrup and a little phosphoric acid

PrepTutorEJDIC

〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥
〈U〉リン酸塩 / 《複数形で》リン酸肥料

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1. 尿素サイクル障害：管理 urea cycle disorders management
2. 尿素サイクル障害：臨床的特徴および診断 urea cycle disorders clinical features and diagnosis

English Journal

Molecular characterization of carbamoyl-phosphate synthetase (CPS1) deficiency using human recombinant CPS1 as a key tool.

Diez-Fernandez C1, Martínez AI, Pekkala S, Barcelona B, Pérez-Arellano I, Guadalajara AM, Summar M, Cervera J, Rubio V.Author information 1Instituto de Biomedicina de Valencia, IBV-CSIC, Valencia, Spain.AbstractThe 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 synthetase 1 (CPS1), a very large, complex, and fastidious enzyme. The kinetic and molecular properties of recombinant CPS1 are essentially the same as for natural human CPS1. Glycerol partially replaces the essential activator N-acetyl-l-glutamate (NAG), opening possibilities for treating CPS1D due to NAG site defects. The value of our expression system for elucidating the effects of mutations is demonstrated with eight clinical CPS1 mutations. Five of these mutations decreased enzyme stability, two mutations drastically hampered catalysis, and one vastly impaired NAG activation. In contrast, the polymorphisms p.Thr344Ala and p.Gly1376Ser had no detectable effects. Site-limited proteolysis proved the correctness of the working model for the human CPS1 domain architecture generally used for rationalizing the mutations effects. NAG and its analogue and orphan drug N-carbamoyl-l-glutamate, protected human CPS1 against proteolytic and thermal inactivation in the presence of MgATP, raising hopes of treating CPS1D by chemical chaperoning with N-carbamoyl-l-glutamate.
Human mutation.Hum Mutat.2013 Aug;34(8):1149-59. doi: 10.1002/humu.22349. Epub 2013 May 28.
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 sys
PMID 23649895

Crystal structure of the N-acetyltransferase domain of human N-acetyl-L-glutamate synthase in complex with N-acetyl-L-glutamate provides insights into its catalytic and regulatory mechanisms.

Zhao G1, Jin Z, Allewell NM, Tuchman M, Shi D.Author information 1Center for Genetic Medicine Research and Department of Integrative Systems Biology, Children's National Medical Center, The George Washington University, Washington, DC, United States of America.AbstractN-acetylglutamate synthase (NAGS) catalyzes the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate (NAG), an obligate cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle. NAGS deficiency results in elevated levels of plasma ammonia which is neurotoxic. We report herein the first crystal structure of human NAGS, that of the catalytic N-acetyltransferase (hNAT) domain with N-acetyl-L-glutamate bound at 2.1 Å resolution. Functional studies indicate that the hNAT domain retains catalytic activity in the absence of the amino acid kinase (AAK) domain. Instead, the major functions of the AAK domain appear to be providing a binding site for the allosteric activator, L-arginine, and an N-terminal proline-rich motif that is likely to function in signal transduction to CPS1. Crystalline hNAT forms a dimer similar to the NAT-NAT dimers that form in crystals of bifunctional N-acetylglutamate synthase/kinase (NAGS/K) from Maricaulis maris and also exists as a dimer in solution. The structure of the NAG binding site, in combination with mutagenesis studies, provide insights into the catalytic mechanism. We also show that native NAGS from human and mouse exists in tetrameric form, similar to those of bifunctional NAGS/K.
PloS one.PLoS One.2013 Jul 24;8(7):e70369. doi: 10.1371/journal.pone.0070369. Print 2013.
N-acetylglutamate synthase (NAGS) catalyzes the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate (NAG), an obligate cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle. NAGS deficiency results in elevated levels of plasma ammonia which is neurotoxic. We report he
PMID 23894642

Carbamoyl phosphate synthetase 1 deficiency in Italy: clinical and genetic findings in a heterogeneous cohort.

Funghini S1, Thusberg J, Spada M, Gasperini S, Parini R, Ventura L, Meli C, De Cosmo L, Sibilio M, Mooney SD, Guerrini R, Donati MA, Morrone A.Author information 1Metabolic and Muscular Unit, Clinic of Paediatric Neurology, Meyer Children's Hospital, Florence, Italy.AbstractCarbamoyl Phosphate Synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder, potentially leading to lethal hyperammonemia. Based on the age of onset, there are two distinct phenotypes: neonatal and late form. The CPS1 enzyme, located in the mitochondrial matrix of hepatocytes and epithelial cells of intestinal mucosa, is encoded by the CPS1 gene. At present more than 220 clear-cut genetic lesions leading to CPS1D have been reported. As most of them are private mutations diagnosis is complicated. Here we report an overview of the main clinical findings and biochemical and molecular data of 13 CPS1D Italian patients. In two of them, one with the neonatal form and one with the late form, cadaveric auxiliary liver transplant was performed. Mutation analysis in these patients identified 17 genetic lesions, 9 of which were new confirming their "private" nature. Seven of the newly identified mutations were missense/nonsense changes. In order to study their protein level effects, we performed an in silico analysis whose results indicate that the amino acid substitutions occur at evolutionary conserved positions and affect residues necessary for enzyme stability or function.
Gene.Gene.2012 Feb 10;493(2):228-34. doi: 10.1016/j.gene.2011.11.052. Epub 2011 Dec 7.
Carbamoyl Phosphate Synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder, potentially leading to lethal hyperammonemia. Based on the age of onset, there are two distinct phenotypes: neonatal and late form. The CPS1 enzyme, located in the mitochondrial matrix of hepatocyt
PMID 22173106

Japanese Journal

カルバミルリン酸合成酵素I(CPS I)欠損症の遺伝子解析

日本先天代謝異常学会雑誌 15(2), 136, 1999-10-22
NAID 10018938664

持続的血液濾過透析が有効であったカルバミルリン酸合成酵素I欠損症の1乳児例

日本先天代謝異常学会雑誌 15(2), 135, 1999-10-22
NAID 10018938663

A carbamyl phosphate synthetase I deficiency with no detectable messenger RNA activity

Acta Paediatr Jpn 26, 262-265, 1994
NAID 30029942756

★リンクテーブル★

リンク元	「カルバモイルリン酸合成酵素欠損症」「カルバミルリン酸合成酵素欠損症」
関連記事	「deficiency」「phosphate」「synthetase」「carbamyl phosphate」