Base de dados : MEDLINE
Pesquisa : C10.228.140.163.100.937.249 [Categoria DeCS]
Referências encontradas : 59 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 6 ir para página                

  1 / 59 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28658158
[Au] Autor:Yang X; Shi J; Lei H; Xia B; Mu D
[Ad] Endereço:aDepartment of Pediatrics, West China Second University Hospital bKey Laboratory of Obstetric & Gynaecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, Sichuan, China.
[Ti] Título:Neonatal-onset carbamoyl phosphate synthetase I deficiency: A case report.
[So] Source:Medicine (Baltimore);96(26):e7365, 2017 Jun.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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-onset CPS1D with nonspecific clinical manifestations and deteriorating rapidly. Poor feeding, low activity, and tachypnoea were observed, with rapid progression on day 2 after birth. Severe systematic infection was considered first. However, blood culture and cerebrospinal fluid examination were negative. Symptoms were relief temporarily. Then seizure and tachypnoea reappeared as intravenous amino acids were provided. Further examination indicated severe hyperammonemia (serum ammonia level >500mmol/L). Brain MRI showed diffused white matter lesions. DIAGNOSES: Genetic analysis revealed 2 heterozygous mutations in the CPS1 gene: c.2407C>G (p.803, R>G) in exon 20 and C.323G>A (p.108, G>E) in exon 4. The diagnosis of CSP1D was confirmed. INTERVENTIONS: Fasting, the withdrawal of amino acids and plans to treat hyperammonemia were immediately implemented. OUTCOMES: The parents decided to discontinue medical care. LESSONS: Many CPS1D patients died before the diagnoses are confirmed due to its sudden onset, rapid deterioration, atypical symptoms, and low morbidity. Once hyperammonemia is confirmed, blood and urea amino acid analysis in combination with genetic examinations should be performed as early as possible, this approach would help establish diagnoses at an early stage and thus contribute to reducing mortality and improving prognosis.
[Mh] Termos MeSH primário: Doença da Deficiência da Carbamoil-Fosfato Sintase I/diagnóstico
[Mh] Termos MeSH secundário: Encéfalo/diagnóstico por imagem
Carbamoil-Fosfato Sintase (Amônia)/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/terapia
Diagnóstico Precoce
Feminino
Seres Humanos
Recém-Nascido
Recusa do Paciente ao Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 6.3.4.16 (Carbamoyl-Phosphate Synthase (Ammonia))
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007365


  2 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28281899
[Au] Autor:Diez-Fernandez C; Häberle J
[Ad] Endereço:a Division of Metabolism , University Children's Hospital Zurich and Children's Research Center , Zurich , Switzerland.
[Ti] Título:Targeting CPS1 in the treatment of Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea cycle disorder.
[So] Source:Expert Opin Ther Targets;21(4):391-399, 2017 Apr.
[Is] ISSN:1744-7631
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Carbamoyl phosphate synthetase 1 (CPS1) deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder (UCD), which can lead to life-threatening hyperammonemia. Unless promptly treated, it can result in encephalopathy, coma and death, or intellectual disability in surviving patients. Over recent decades, therapies for CPS1D have barely improved leaving the management of these patients largely unchanged. Additionally, in many cases, current management (protein-restriction and supplementation with citrulline and/or arginine and ammonia scavengers) is insufficient for achieving metabolic stability, highlighting the importance of developing alternative therapeutic approaches. Areas covered: After describing UCDs and CPS1D, we give an overview of the structure- function of CPS1. We then describe current management and potential novel treatments including N-carbamoyl-L-glutamate (NCG), pharmacological chaperones, and gene therapy to treat hyperammonemia. Expert opinion: Probably, the first novel CPS1D therapies to reach the clinics will be the already commercial substance NCG, which is the standard treatment for N-acetylglutamate synthase deficiency and has been proven to rescue specific CPS1D mutations. Pharmacological chaperones and gene therapy are under development too, but these two technologies still have key challenges to be overcome. In addition, current experimental therapies will hopefully add further treatment options.
[Mh] Termos MeSH primário: Carbamoil-Fosfato Sintase (Amônia)/metabolismo
Doença da Deficiência da Carbamoil-Fosfato Sintase I/terapia
Glutamatos/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Carbamoil-Fosfato Sintase (Amônia)/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/fisiopatologia
Terapia Genética/métodos
Seres Humanos
Chaperonas Moleculares/farmacologia
Mutação
Distúrbios Congênitos do Ciclo da Ureia/fisiopatologia
Distúrbios Congênitos do Ciclo da Ureia/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Glutamates); 0 (Molecular Chaperones); 1188-38-1 (N-carbamylglutamate); EC 6.3.4.16 (Carbamoyl-Phosphate Synthase (Ammonia))
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1080/14728222.2017.1294685


  3 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28007335
[Au] Autor:Shi D; Zhao G; Ah Mew N; Tuchman M
[Ad] Endereço:Center for Genetic Medicine Research, Department of Integrative Systems Biology, Children's Research Institute, Children's National Health System, The George Washington University, Washington, DC 20010, USA. Electronic address: dshi@childrensnational.org.
[Ti] Título:Precision medicine in rare disease: Mechanisms of disparate effects of N-carbamyl-l-glutamate on mutant CPS1 enzymes.
[So] Source:Mol Genet Metab;120(3):198-206, 2017 Mar.
[Is] ISSN:1096-7206
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study documents the disparate therapeutic effect of N-carbamyl-l-glutamate (NCG) in the activation of two different disease-causing mutants of carbamyl phosphate synthetase 1 (CPS1). We investigated the effects of NCG on purified recombinant wild-type (WT) mouse CPS1 and its human corresponding E1034G (increased ureagenesis on NCG) and M792I (decreased ureagenesis on NCG) mutants. NCG activates WT CPS1 sub-optimally compared to NAG. Similar to NAG, NCG, in combination with MgATP, stabilizes the enzyme, but competes with NAG binding to the enzyme. NCG supplementation activates available E1034G mutant CPS1 molecules not bound to NAG enhancing ureagenesis. Conversely, NCG competes with NAG binding to the scarce M792I mutant enzyme further decreasing residual ureagenesis. These results correlate with the respective patient's response to NCG. Particular caution should be taken in the administration of NCG to patients with hyperammonemia before their molecular bases of their urea cycle disorders is known.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/administração & dosagem
Carbamoil-Fosfato Sintase (Amônia)/química
Carbamoil-Fosfato Sintase (Amônia)/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/tratamento farmacológico
Glutamatos/administração & dosagem
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/farmacologia
Animais
Doença da Deficiência da Carbamoil-Fosfato Sintase I/enzimologia
Quimioterapia Combinada
Feminino
Glutamatos/farmacologia
Seres Humanos
Masculino
Camundongos
Mutação
Medicina de Precisão
Estabilidade Proteica/efeitos dos fármacos
Estrutura Terciária de Proteína
Doenças Raras/tratamento farmacológico
Doenças Raras/enzimologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glutamates); 1188-38-1 (N-carbamylglutamate); 8L70Q75FXE (Adenosine Triphosphate); EC 6.3.4.16 (Carbamoyl-Phosphate Synthase (Ammonia))
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161224
[St] Status:MEDLINE


  4 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27834067
[Au] Autor:Choi R; Park HD; Yang M; Ki CS; Lee SY; Kim JW; Song J; Chang YS; Park WS
[Ad] Endereço:Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
[Ti] Título:Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing.
[So] Source:Ann Lab Med;37(1):58-62, 2017 Jan.
[Is] ISSN:2234-3814
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 µmol/L; reference range, 11.2-48.2 µmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 µmol/L; reference range, 131-710 µmol/L) and glutamine (5,777 µmol/L; reference range, 376-709 µmol/L), whereas that of citrulline was decreased (2 µmol/L; reference range, 10-45 µmol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.
[Mh] Termos MeSH primário: Carbamoil-Fosfato Sintase (Amônia)/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/genética
[Mh] Termos MeSH secundário: Sequência de Bases
Carbamoil-Fosfato Sintase (Amônia)/química
Doença da Deficiência da Carbamoil-Fosfato Sintase I/diagnóstico
Códon sem Sentido
Éxons
Feminino
Mutação da Fase de Leitura
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Recém-Nascido
República da Coreia
Análise de Sequência de DNA
Distúrbios Congênitos do Ciclo da Ureia/diagnóstico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Nonsense); EC 6.3.4.16 (Carbamoyl-Phosphate Synthase (Ammonia))
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170224
[Lr] Data última revisão:
170224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161112
[St] Status:MEDLINE
[do] DOI:10.3343/alm.2017.37.1.58


  5 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27150549
[Au] Autor:Yamaguchi M; Kataoka TR; Shibayama T; Fukuda A; Nakazawa A; Minamiguchi S; Sakurai T; Miyagawa-Hayashino A; Yorifuji T; Kasahara M; Uemoto S; Haga H
[Ad] Endereço:Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
[Ti] Título:Loss of Hep Par 1 immunoreactivity in the livers of patients with carbamoyl phosphate synthetase 1 deficiency.
[So] Source:Pathol Int;66(6):333-6, 2016 Jun.
[Is] ISSN:1440-1827
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:The hepatocyte paraffin 1 (Hep Par 1) antibody is widely used as a hepatocyte marker, recognizing carbamoyl phosphate synthetase 1 (CPS1), an essential component of the urea cycle. Various missense, nonsense, and frameshift mutations occur in the CPS1 gene. In neonatal patients with homozygous CPS1 deficiency (CPS1D), urea cycle defects with resulting severe hyperammonemia can be fatal, though liver transplantation provides a complete cure for CPS1D. We performed Hep Par 1 immunostaining in the explanted livers of 10 liver transplant patients with CPS1D. Seven were negative for Hep Par 1 in the hepatocytes and the other three showed normal diffuse granular cytoplasmic staining. As expected, all three Hep Par 1-positive patients had at least one missense mutation, and all four patients who had only nonsense or frameshift mutations were Hep Par 1-negative. The other three patients were unexpectedly negative for Hep Par 1, even though each had one missense mutation. These results suggest that CPS1D can be related to the loss of Hep Par 1 reactivity due to the loss of protein production, a one amino acid substitution resulting in an abortive protein product, or both. Hep Par 1 immunohistochemistry can be used as a simple method to confirm CPS1D.
[Mh] Termos MeSH primário: Antígenos de Neoplasias/metabolismo
Doença da Deficiência da Carbamoil-Fosfato Sintase I/metabolismo
Hepatócitos/metabolismo
Fígado/metabolismo
[Mh] Termos MeSH secundário: Doença da Deficiência da Carbamoil-Fosfato Sintase I/cirurgia
Feminino
Seres Humanos
Imuno-Histoquímica
Lactente
Transplante de Fígado
Masculino
Mutação de Sentido Incorreto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (HepPar-1 protein, human)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170223
[Lr] Data última revisão:
170223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160507
[St] Status:MEDLINE
[do] DOI:10.1111/pin.12414


  6 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26440671
[Au] Autor:Ali EZ; Khalid MK; Yunus ZM; Yakob Y; Chin CB; Abd Latif K; Hock NL
[Ad] Endereço:Molecular Diagnostics and Protein Unit, Specialised Diagnostics Centre, Institute for Medical Research, Jalan Pahang, 50588, Kuala Lumpur, Malaysia. erniez1980@gmail.com.
[Ti] Título:Carbamoylphosphate synthetase 1 (CPS1) deficiency: clinical, biochemical, and molecular characterization in Malaysian patients.
[So] Source:Eur J Pediatr;175(3):339-46, 2016 Mar.
[Is] ISSN:1432-1076
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare autosomal recessive disorder of ureagenesis presenting as life-threatening hyperammonemia. In this study, we present the main clinical features and biochemical and molecular data of six Malaysian patients with CPS1 deficiency. All the patients have neonatal-onset symptoms, initially diagnosed as infections before hyperammonemia was recognized. They have typical biochemical findings of hyperglutaminemia, hypocitrullinemia, and low to normal urinary excretion of orotate. One neonate succumbed to the first hyperammonemic decompensation. Five neonatal survivors received long-term treatment consisting of dietary protein restriction and ammonia-scavenging drugs. They have delayed neurocognitive development of varying severity. Genetic analysis revealed eight mutations in CPS1 gene, five of which were not previously reported. Five mutations were missense changes while another three were predicted to create premature stop codons. In silico analyses showed that these new mutations affected different CPS1 enzyme domains and were predicted to interrupt interactions at enzyme active sites, disturb local enzyme conformation, and destabilize assembly of intact enzyme complex. CONCLUSION: All mutations are private except one mutation; p.Ile1254Phe was found in three unrelated families. Identification of a recurrent p.Ile1254Phe mutation suggests the presence of a common and unique mutation in our population. Our study also expands the mutational spectrum of the CPS1 gene.
[Mh] Termos MeSH primário: Amônia/sangue
Carbamoil-Fosfato Sintase (Amônia)/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/diagnóstico
Hiperamonemia/etiologia
[Mh] Termos MeSH secundário: Grupo com Ancestrais do Continente Asiático/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/genética
Simulação por Computador
Feminino
Testes Genéticos/métodos
Seres Humanos
Hiperamonemia/sangue
Hiperamonemia/genética
Recém-Nascido
Imagem por Ressonância Magnética
Malásia
Masculino
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
7664-41-7 (Ammonia); EC 6.3.4.16 (Carbamoyl-Phosphate Synthase (Ammonia))
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151007
[St] Status:MEDLINE
[do] DOI:10.1007/s00431-015-2644-z


  7 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26592762
[Au] Autor:de Cima S; Polo LM; Díez-Fernández C; Martínez AI; Cervera J; Fita I; Rubio V
[Ad] Endereço:Instituto de Biomedicina de Valencia del Consejo Superior de Investigaciones Científicas (IBV-CSIC), Jaime Roig 11, 46010 Valencia, Spain.
[Ti] Título:Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis.
[So] Source:Sci Rep;5:16950, 2015 Nov 23.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo: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 binding at the C-terminal domain of CPS1, NAG triggers long-range conformational changes affecting the two distant phosphorylation domains. These changes, concerted with the binding of nucleotides, result in a dramatic remodeling that stabilizes the catalytically competent conformation and the building of the ~35 Å-long tunnel that allows migration of the carbamate intermediate from its site of formation to the second phosphorylation site, where carbamoyl phosphate is produced. These structures allow rationalizing the effects of mutations found in patients with CPS1 deficiency (presenting hyperammonemia, mental retardation and even death), as exemplified here for some mutations.
[Mh] Termos MeSH primário: Amônia/química
Carbamoil-Fosfato Sintase (Amônia)/química
Carbamoil-Fosfato/química
Glutamatos/química
Ureia/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Amônia/metabolismo
Animais
Baculoviridae/genética
Baculoviridae/metabolismo
Carbamoil-Fosfato Sintase (Amônia)/genética
Carbamoil-Fosfato Sintase (Amônia)/metabolismo
Doença da Deficiência da Carbamoil-Fosfato Sintase I/enzimologia
Doença da Deficiência da Carbamoil-Fosfato Sintase I/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/patologia
Carbamoil-Fosfato/metabolismo
Clonagem Molecular
Cristalografia por Raios X
Expressão Gênica
Glutamatos/metabolismo
Seres Humanos
Modelos Moleculares
Dados de Sequência Molecular
Mutação
Fosforilação
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Células Sf9
Spodoptera
Especificidade por Substrato
Ureia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Glutamates); 0 (Recombinant Proteins); 590-55-6 (Carbamyl Phosphate); 7664-41-7 (Ammonia); 8W8T17847W (Urea); EC 6.3.4.16 (Carbamoyl-Phosphate Synthase (Ammonia)); MA61H539YZ (N-acetylglutamic acid)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151124
[St] Status:MEDLINE
[do] DOI:10.1038/srep16950


  8 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26059772
[Au] Autor:Díez-Fernández C; Gallego J; Häberle J; Cervera J; Rubio V
[Ad] Endereço:Institute for Biomedicine of Valencia of the Spanish Research Council, Valencia 46010, Spain.
[Ti] Título:The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching On/Off the Urea Cycle.
[So] Source:J Genet Genomics;42(5):249-60, 2015 May 20.
[Is] ISSN:1673-8527
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Carbamoyl phosphate synthetase 1 (CPS1) deficiency (CPS1D) is an inborn error of the urea cycle having autosomal (2q34) recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPS1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPS1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPS1, N-acetyl-L-glutamate (NAG), is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPS1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L-glutamate (a registered drug, the analog of NAG). Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the ß4-α4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPS1.
[Mh] Termos MeSH primário: Amônia/metabolismo
Carbamoil-Fosfato Sintase (Amônia)/química
Carbamoil-Fosfato Sintase (Amônia)/metabolismo
Doença da Deficiência da Carbamoil-Fosfato Sintase I/metabolismo
Ureia/metabolismo
[Mh] Termos MeSH secundário: Carbamoil-Fosfato Sintase (Amônia)/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/enzimologia
Doença da Deficiência da Carbamoil-Fosfato Sintase I/genética
Doença da Deficiência da Carbamoil-Fosfato Sintase I/patologia
Estabilidade Enzimática
Glutamatos/metabolismo
Seres Humanos
Cinética
Simulação de Dinâmica Molecular
Mutação
Estrutura Terciária de Proteína
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Glutamates); 7664-41-7 (Ammonia); 8W8T17847W (Urea); EC 6.3.4.16 (Carbamoyl-Phosphate Synthase (Ammonia)); MA61H539YZ (N-acetylglutamic acid)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150610
[Lr] Data última revisão:
150610
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150611
[St] Status:MEDLINE


  9 / 59 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25941206
[Au] Autor:Nunley S; Ghosh D
[Ad] Endereço:From Nationwide Children's Hospital, Columbus, OH. sunjay.nunley@nationwidechildrens.org.
[Ti] Título:Teaching NeuroImages: MRI findings in carbamoyl phosphate synthetase 1 deficiency.
[So] Source:Neurology;84(18):e138-9, 2015 May 05.
[Is] ISSN:1526-632X
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Doença da Deficiência da Carbamoil-Fosfato Sintase I/patologia
Núcleo Caudado/patologia
Lobo Frontal/patologia
Putamen/patologia
[Mh] Termos MeSH secundário: Pré-Escolar
Feminino
Seres Humanos
Imagem por Ressonância Magnética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1507
[Cu] Atualização por classe:150505
[Lr] Data última revisão:
150505
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150506
[St] Status:MEDLINE
[do] DOI:10.1212/WNL.0000000000001546


  10 / 59 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25852294
[Au] Autor:Foschi FG; Morelli MC; Savini S; Dall'Aglio AC; Lanzi A; Cescon M; Ercolani G; Cucchetti A; Pinna AD; Stefanini GF
[Ad] Endereço:Francesco Giuseppe Foschi, Sara Savini, Anna Chiara Dall'Aglio, Arianna Lanzi, Giuseppe Francesco Stefanini, U.O. Medicina Interna, Ospedale di Faenza, 48018 Faenza, Italy.
[Ti] Título:Urea cycle disorders: a case report of a successful treatment with liver transplant and a literature review.
[So] Source:World J Gastroenterol;21(13):4063-8, 2015 Apr 07.
[Is] ISSN:2219-2840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders (UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.
[Mh] Termos MeSH primário: Doença da Deficiência da Carbamoil-Fosfato Sintase I/cirurgia
Transplante de Fígado
[Mh] Termos MeSH secundário: Adolescente
Doença da Deficiência da Carbamoil-Fosfato Sintase I/complicações
Doença da Deficiência da Carbamoil-Fosfato Sintase I/diagnóstico
Doença da Deficiência da Carbamoil-Fosfato Sintase I/dietoterapia
Dieta com Restrição de Proteínas
Progressão da Doença
Feminino
Seres Humanos
Hiperamonemia/etiologia
Qualidade de Vida
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150409
[St] Status:MEDLINE
[do] DOI:10.3748/wjg.v21.i13.4063



página 1 de 6 ir para página                
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde