Base de dados : MEDLINE
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[PMID]:28592010
[Au] Autor:Guan HZ; Ding Y; Li DX; Dong H; Song JQ; Jin Y; Zhu ZJ; Sun LY; Yang YL
[Ad] Endereço:Department of Neonatology, Shanxi Provincial Children's Hospital, Taiyuan 030013, China.
[Ti] Título:[Clinical diagnosis and treatment of three cases with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome].
[So] Source:Zhonghua Er Ke Za Zhi;55(6):428-433, 2017 Jun 02.
[Is] ISSN:0578-1310
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome. From July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed. The three patients' age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months. All of them presented with intolerance to protein-rich foods from the infant period, development retardation and abnormal posture. Case 1 and 2 had moderate mental retardation. Serum ammonia 25-276 µmol/L (reference range<60 µmol/L), alanine aminotransferase (ALT) 20-139 IU/L (reference range 9-50 IU/L), ornithine 29.12-99.44 µmol/L(reference range 15-100 µmol/L), urinary orotic acid 1.49-29.75 mmol/mol Cr (reference range 0-7 mmol/mol Cr), uracil 6.09-103.97 mmol/mol Cr (reference range 0-1.5 mmol/mol Cr). The cranial MRI revealed lesions in the basal ganglia, abnormal white matter signal, progressive demyelination and cerebral atrophy. On their SLC25A15 gene, a novel homozygous missense mutation c. 416A>G (p.E139G) was identified in case 1, a known pathogenic homozygous nonsense mutation c. 535C>T was found in case 2 and 3. Liver transplantation had been performed when case 1 was 6 years old. Significant improvements were observed in dietary habit, mental and motor functions, and biochemical parameters. After the dietary intervention with the supplements of arginine, L-carnitine, case 2 was improved, spastic paraplegia of case 3 had no mitigation. Liver transplant was recommended. HHH syndrome has an aversion to protein-rich food, and the patients have recurrent vomiting and progressive neurological dysfunction. Clinical diagnosis of HHH syndrome is difficult and patients may present with incomplete biochemical phenotype. The genetic analysis is key for the diagnosis. Depending on their condition, individuals with HHH syndrome can be treated with a low-protein diet, drugs and liver transplantation.
[Mh] Termos MeSH primário: Dieta com Restrição de Proteínas
Hiperamonemia/diagnóstico
Mutação
Ornitina/deficiência
Fenótipo
Distúrbios Congênitos do Ciclo da Ureia/diagnóstico
[Mh] Termos MeSH secundário: Arginina
Grupo com Ancestrais do Continente Asiático
Carnitina
Criança
Pré-Escolar
Testes Genéticos
Homozigoto
Seres Humanos
Lactente
Ornitina/uso terapêutico
Ácido Orótico
Proteínas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); 61H4T033E5 (Orotic Acid); 94ZLA3W45F (Arginine); E524N2IXA3 (Ornithine); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0578-1310.2017.06.007


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[PMID]:28374713
[Au] Autor:Ivanov SV; Lazarenko VA; Ivanov IS; Parfenov IP; Tsukanov AV; Tarabrin DV; Ob''edkov EG
[Ad] Endereço:Kursk State Medical University ,Department of surgical diseases #1.
[Ti] Título:[The influence of 'potassium orotate' on neocollagenogenesis in implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis].
[Ti] Título:Vliyanie orotata kaliya na neokollagenogenez pri implantatsii polipropilenovogo endoproteza i endoproteza iz polipropilena s polimolochnoi kislotoi v eksperimente..
[So] Source:Khirurgiia (Mosk);(3):50-54, 2017.
[Is] ISSN:0023-1207
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:AIM: To study neocollagenogenesis after implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis on background of «potassium orotate¼ administration. MATERIAL AND METHODS: We used two different types of endoprosthesis in the experiment. The first type was made of just polypropylene, the second type was made of polypropylene combined with polylactic acid. Histological examination was performed using polarizing microscopy. Collagen types I and III ratio in connective tissue around the prosthesis was analyzed according to the color that was individual for each type. RESULTS: The results were significantly better in case of collagenogenesis stimulation with Potassium orotate within 30 days and later for one type of endoprosthesis. Also we revealed that collagenogenesis and paraprosthesis capsule formation were more active in case of combined endoprosthesis. We revealed stimulating action of «Potassium Orotate¼ for collegenogenesis process, this fact was proved by increased collagen I/III ratio. CONCLUSION: Optimization of collagenogenesis was based on persistent 1,37-fold increase of collagen I/III ratio in case of combined endoprosthesis after 90 days. It was manifested by accelerated formation of connective tissue capsule and facilitated early isolation of the implant from surrounding tissues.
[Mh] Termos MeSH primário: Colágeno/metabolismo
Tecido Conjuntivo
Implantes Experimentais
Ácido Orótico
Poliésteres/farmacologia
Polipropilenos/farmacologia
Implante de Prótese/instrumentação
Regeneração/efeitos dos fármacos
[Mh] Termos MeSH secundário: Experimentação Animal
Animais
Materiais Biocompatíveis/metabolismo
Materiais Biocompatíveis/farmacologia
Disponibilidade Biológica
Tecido Conjuntivo/efeitos dos fármacos
Tecido Conjuntivo/metabolismo
Tecido Conjuntivo/patologia
Camundongos
Ácido Orótico/metabolismo
Ácido Orótico/farmacologia
Compostos de Potássio/metabolismo
Compostos de Potássio/farmacologia
Implante de Prótese/métodos
Regeneração/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biocompatible Materials); 0 (Polyesters); 0 (Polypropylenes); 0 (Potassium Compounds); 459TN2L5F5 (poly(lactide)); 61H4T033E5 (Orotic Acid); 9007-34-5 (Collagen)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.17116/hirurgia2017350-54


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[PMID]:28290772
[Au] Autor:Tani S; Yuki S; Kunitake E; Sumitani JI; Kawaguchi T
[Ad] Endereço:a Graduate School of Life and Environmental Sciences , Osaka Prefecture University , Sakai , Japan.
[Ti] Título:Dipeptidyl peptidase IV is involved in the cellulose-responsive induction of cellulose biomass-degrading enzyme genes in Aspergillus aculeatus.
[So] Source:Biosci Biotechnol Biochem;81(6):1227-1234, 2017 Jun.
[Is] ISSN:1347-6947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We screened for factors involved in the cellulose-responsive induction of cellulose biomass-degrading enzyme genes from approximately 12,000 Aspergillus aculeatus T-DNA insertion mutants harboring a transcriptional fusion between the FIII-avicelase gene (cbhI) promoter and the orotidine 5'-monophosphate decarboxylase gene. Analysis of 5-fluoroorodic acid (5-FOA) sensitivity, cellulose utilization, and cbhI expression of the mutants revealed that a mutant harboring T-DNA at the dipeptidyl peptidase IV (dppIV) locus had acquired 5-FOA resistance and was deficient in cellulose utilization and cbhI expression. The deletion of dppIV resulted in a significant reduction in the cellulose-responsive expression of both cbhI as well as genes controlled by XlnR-independent and XlnR-dependent signaling pathways at an early phase in A. aculeatus. In contrast, the dppIV deletion did not affect the xylose-responsive expression of genes under the control of XlnR. These results demonstrate that DppIV participates in cellulose-responsive induction in A. aculeatus.
[Mh] Termos MeSH primário: Aspergillus/genética
Celulases/genética
Celulose/metabolismo
Dipeptidil Peptidase 4/genética
Proteínas Fúngicas/genética
Regulação Fúngica da Expressão Gênica
Orotidina-5´-Fosfato Descarboxilase/genética
[Mh] Termos MeSH secundário: Aspergillus/efeitos dos fármacos
Aspergillus/enzimologia
Celulases/metabolismo
Celulose/farmacologia
DNA Bacteriano/genética
DNA Bacteriano/metabolismo
Dipeptidil Peptidase 4/agonistas
Dipeptidil Peptidase 4/metabolismo
Proteínas Fúngicas/metabolismo
Deleção de Genes
Mutagênese Insercional
Ácido Orótico/análogos & derivados
Ácido Orótico/metabolismo
Ácido Orótico/farmacologia
Orotidina-5'-Fosfato Descarboxilase/metabolismo
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Transdução de Sinais
Xilose/metabolismo
Xilose/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial); 0 (Fungal Proteins); 0 (Recombinant Fusion Proteins); 0 (T-DNA); 61H4T033E5 (Orotic Acid); 7IA9OUC93E (5-fluoroorotic acid); 9004-34-6 (Cellulose); A1TA934AKO (Xylose); EC 3.2.1.- (Cellulases); EC 3.4.14.5 (Dipeptidyl Peptidase 4); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1080/09168451.2017.1295800


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[PMID]:28225618
[Au] Autor:Lewis CA; Shen L; Yang W; Wolfenden R
[Ad] Endereço:Department of Biochemistry and Biophysics, University of North Carolina , Chapel Hill, North Carolina 27599-7260, United States.
[Ti] Título:Three Pyrimidine Decarboxylations in the Absence of a Catalyst.
[So] Source:Biochemistry;56(10):1498-1503, 2017 Mar 14.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The epigenetic modification of DNA by 5-methylation of cytosine residues can be reversed by the action of the TET family of dioxygenases that oxidize the methyl group to produce 5-carboxycytosine (5caC), which can be converted to cytosine in a final decarboxylation step. Likewise, 5-carboxyuracil (5caU) is decarboxylated to uracil in the last step in pyrimidine salvage. In view of the extreme difficulty of decarboxylating derivatives of orotic acid (6caU), it seemed desirable to establish the rates of decarboxylation of 5caC and 5caU in the absence of a catalyst. Arrhenius analysis of experiments performed at elevated temperatures indicates that 5caU decomposes with a rate constant of 1.1 × 10 s (ΔH = 25 kcal/mol) in a neutral solution at 25 °C. The decomposition of 5caC is somewhat slower (k = 5.0 × 10 s ; ΔH = 27 kcal/mol) and leads to the initial accumulation of cytosine as an intermediate, followed by the relatively rapid deamination of cytosine (k = 1.9 × 10 s ; ΔH = 23.4 kcal/mol). Both 5caC and 5caU are decarboxylated many orders of magnitude more rapidly than 6caU is (k = 1.3 × 10 s ). Ab initio simulations indicate that in all three cases, the favored route of spontaneous decarboxylation in water involves direct elimination of CO with the assistance of an explicit water molecule.
[Mh] Termos MeSH primário: Dióxido de Carbono/química
Citosina/química
Ácido Orótico/química
Uracila/química
Água/química
[Mh] Termos MeSH secundário: DNA/química
Metilação de DNA
Descarboxilação
Hidrólise
Cinética
Oxirredução
Soluções
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Solutions); 059QF0KO0R (Water); 142M471B3J (Carbon Dioxide); 56HH86ZVCT (Uracil); 61H4T033E5 (Orotic Acid); 8J337D1HZY (Cytosine); 9007-49-2 (DNA)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00055


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[PMID]:28205048
[Au] Autor:Wortmann SB; Chen MA; Colombo R; Pontoglio A; Alhaddad B; Botto LD; Yuzyuk T; Coughlin CR; Descartes M; Grunewald S; Maranda B; Mills PB; Pitt J; Potente C; Rodenburg R; Kluijtmans LA; Sampath S; Pai EF; Wevers RA; Tiller GE; and additional individual contributors
[Ad] Endereço:Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), Mullner Hauptstrasse 48, 5020, Salzburg, Austria. s.wortmann-hagemann@salk.at.
[Ti] Título:Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences.
[So] Source:J Inherit Metab Dis;40(3):423-431, 2017 May.
[Is] ISSN:1573-2665
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue. METHODS AND RESULTS: We identified mild and isolated orotic aciduria in 11 unrelated individuals with diverse clinical signs and symptoms, the most common denominator being intellectual disability/developmental delay. Of note, none had blood count abnormalities, relevant hyperammonemia or altered plasma amino acid profile. All individuals were found to have heterozygous alterations in UMPS. Four of these variants were predicted to be null alleles with complete loss of function. The remaining variants were missense changes and predicted to be damaging to the normal encoded protein. Interestingly, family screening revealed heterozygous UMPS variants in combination with mild orotic aciduria in 19 clinically asymptomatic family members. CONCLUSIONS: We therefore conclude that heterozygous UMPS-mutations can lead to mild and isolated orotic aciduria without clinical consequence. Partial UMPS-deficiency should be included in the differential diagnosis of mild orotic aciduria. The discovery of heterozygotes manifesting clinical symptoms such as hypotonia and developmental delay are likely due to ascertainment bias.
[Mh] Termos MeSH primário: Complexos Multienzimáticos/genética
Complexos Multienzimáticos/metabolismo
Orotato Fosforribosiltransferase/deficiência
Orotidina-5´-Fosfato Descarboxilase/deficiência
Erros Inatos do Metabolismo da Purina-Pirimidina/metabolismo
[Mh] Termos MeSH secundário: Anemia Megaloblástica/genética
Anemia Megaloblástica/metabolismo
Criança
Pré-Escolar
Feminino
Heterozigoto
Seres Humanos
Lactente
Deficiência Intelectual/genética
Deficiência Intelectual/metabolismo
Masculino
Mutação/genética
Orotato Fosforribosiltransferase/genética
Orotato Fosforribosiltransferase/metabolismo
Ácido Orótico/metabolismo
Orotidina-5'-Fosfato Descarboxilase/genética
Orotidina-5'-Fosfato Descarboxilase/metabolismo
Erros Inatos do Metabolismo da Purina-Pirimidina/genética
Pirimidinas/metabolismo
Distúrbios Congênitos do Ciclo da Ureia/genética
Distúrbios Congênitos do Ciclo da Ureia/metabolismo
Uridina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Multienzyme Complexes); 0 (Pyrimidines); 61H4T033E5 (Orotic Acid); 74870-74-9 (uridine 5'-monophosphate synthase); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase); K8CXK5Q32L (pyrimidine); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1007/s10545-017-0015-9


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[PMID]:28155119
[Au] Autor:Bambling M; Edwards SC; Hall S; Vitetta L
[Ad] Endereço:Faculty of Medicine, The University of Queensland, 288 Herston Road, Herston, Brisbane, QLD, 4006, Australia. m.bambling@uq.edu.au.
[Ti] Título:A combination of probiotics and magnesium orotate attenuate depression in a small SSRI resistant cohort: an intestinal anti-inflammatory response is suggested.
[So] Source:Inflammopharmacology;25(2):271-274, 2017 Apr.
[Is] ISSN:1568-5608
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Approximately, one-third of those who develop major depression will have a poor response to treatment and over time can become treatment resistant. Intestinal dysbiosis has been implicated in depression with systemic inflammation and vagal and enteric nerve impairment. We report on a sequel pilot study (n = 12) with a combination probiotics/magnesium orotate formulation adjuvant administered with SSRIs for treatment resistant depression. At the end of an 8-week intervention mean changes for depression scores and quality of life in the group was clinically significantly improved (p < 0.001) with all but 4 participants experiencing a benefit. An intestinal anti-inflammatory response was suggested. At 16-weeks follow-up while still on SSRI medications, the group had relapsed after cessation of the test intervention.
[Mh] Termos MeSH primário: Anti-Inflamatórios/administração & dosagem
Transtorno Depressivo Resistente a Tratamento/diagnóstico
Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico
Ácido Orótico/análogos & derivados
Probióticos/administração & dosagem
Inibidores da Captação de Serotonina/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Antidepressivos/administração & dosagem
Estudos de Coortes
Quimioterapia Combinada
Feminino
Seguimentos
Trato Gastrointestinal/efeitos dos fármacos
Trato Gastrointestinal/microbiologia
Trato Gastrointestinal/patologia
Seres Humanos
Masculino
Meia-Idade
Ácido Orótico/administração & dosagem
Projetos Piloto
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antidepressive Agents); 0 (Serotonin Uptake Inhibitors); 61H4T033E5 (Orotic Acid); GI96W46M5A (magnesium orotate)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE
[do] DOI:10.1007/s10787-017-0311-x


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[PMID]:28118956
[Au] Autor:Inaoka DK; Iida M; Hashimoto S; Tabuchi T; Kuranaga T; Balogun EO; Honma T; Tanaka A; Harada S; Nara T; Kita K; Inoue M
[Ad] Endereço:School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
[Ti] Título:Design and synthesis of potent substrate-based inhibitors of the Trypanosoma cruzi dihydroorotate dehydrogenase.
[So] Source:Bioorg Med Chem;25(4):1465-1470, 2017 Feb 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi, is the leading cause of heart disease in Latin America. T. cruzi dihydroorotate dehydrogenase (DHODH), which catalyzes the production of orotate, was demonstrated to be essential for T. cruzi survival, and thus has been considered as a potential drug target to combat Chagas disease. Here we report the design and synthesis of 75 compounds based on the orotate structure. A comprehensive structure-activity relationship (SAR) study revealed two 5-substituted orotate analogues (5u and 5v) that exhibit K values of several ten nanomolar level and a selectivity of more than 30,000-fold over human DHODH. The information presented here will be invaluable in the search for next-generation drug leads for Chagas disease.
[Mh] Termos MeSH primário: Desenho de Drogas
Inibidores Enzimáticos/farmacologia
Ácido Orótico/farmacologia
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores
Trypanosoma cruzi/efeitos dos fármacos
[Mh] Termos MeSH secundário: Doença de Chagas/tratamento farmacológico
Doença de Chagas/parasitologia
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Seres Humanos
Estrutura Molecular
Ácido Orótico/síntese química
Ácido Orótico/química
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo
Relação Estrutura-Atividade
Trypanosoma cruzi/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 61H4T033E5 (Orotic Acid); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.5.2 (dihydroorotate dehydrogenase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE


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[PMID]:28012135
[Au] Autor:Liu Y; Shi D; Tian Y; Liu Y; Zhan Q; Xu J; Wang J; Xue C
[Ad] Endereço:College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
[Ti] Título:Eicosapentaenoic Acid-Enriched Phosphatidylcholine Attenuated Hepatic Steatosis Through Regulation of Cholesterol Metabolism in Rats with Nonalcoholic Fatty Liver Disease.
[So] Source:Lipids;52(2):119-127, 2017 Feb.
[Is] ISSN:1558-9307
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1% orotic acid. To determine the possible cholesterol metabolism promoting mechanism of EPA-PC, we analyzed the transcription of key genes and transcriptional factors involved in hepatic cholesterol metabolism. EPA-PC dramatically alleviated hepatic lipid accumulation, reduced the serum TC concentration, and elevated HDLC levels in NAFLD rats. Fecal neutral cholesterol excretion was also promoted by EPA-PC administration. Additionally, EPA-PC decreased the mRNA expression of hydroxymethyl glutaric acid acyl (HMGR) and cholesterol 7α-hydroxylase (CYP7A), and increased the transcription of sterol carrying protein 2 (SCP2). Moreover, EPA-PC stimulated the transcription of peroxisome proliferators-activated receptor α (PPARα) and adenosine monophosphate activated protein kinase (AMPK) as well as its modulators, liver kinase B1 (LKB1) and Ca /calmodulin-dependent kinase kinase (CAMKK). Based on the results, the promoting effects of EPA-PC on NAFLD may be partly associated with the suppression of cholesterol synthesis via HMGR inhibition and the enhancement of fecal cholesterol excretion through increased SCP2 transcription. The underlying mechanism may involve stimulation of PPARα and AMPK.
[Mh] Termos MeSH primário: Colesterol/sangue
Ácido Eicosapentaenoico/administração & dosagem
Perfilação da Expressão Gênica/métodos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
Ácido Orótico/efeitos adversos
Fosfatidilcolinas/química
[Mh] Termos MeSH secundário: Animais
Proteínas de Transporte/genética
Colesterol 7-alfa-Hidroxilase/genética
Modelos Animais de Doenças
Ácido Eicosapentaenoico/química
Ácido Eicosapentaenoico/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Hidroximetilglutaril-CoA Redutases/genética
Masculino
Hepatopatia Gordurosa não Alcoólica/induzido quimicamente
Hepatopatia Gordurosa não Alcoólica/metabolismo
Distribuição Aleatória
Ratos
Ratos Wistar
Pepinos-do-Mar/química
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Phosphatidylcholines); 0 (sterol carrier proteins); 61H4T033E5 (Orotic Acid); 97C5T2UQ7J (Cholesterol); AAN7QOV9EA (Eicosapentaenoic Acid); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171105
[Lr] Data última revisão:
171105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161225
[St] Status:MEDLINE
[do] DOI:10.1007/s11745-016-4222-1


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[PMID]:27906623
[Au] Autor:Löffler M; Carrey EA; Zameitat E
[Ad] Endereço:a Institute of Physiological Chemistry, Faculty of Medicine, Philipps University Marburg , Marburg , Germany.
[Ti] Título:Orotate (orotic acid): An essential and versatile molecule.
[So] Source:Nucleosides Nucleotides Nucleic Acids;35(10-12):566-577, 2016 Dec.
[Is] ISSN:1532-2335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Orotate (OA) is well-known as a precursor in biosynthesis of pyrimidines; in mammals it is released from the mitochondrial dihydroorotate dehydrogenase (DHODH) for conversion to UMP by the cytoplasmic UMP synthase enzyme. OA is also a normal part of the diet, being found in milk and dairy products, and it is converted to uridine for use in the pyrimidine salvage pathway predominantly in liver, kidney and erythrocytes. Early research into nutrition identified orotate as "vitamin B13," and its use as a complex with organic cations or metal ions was promulgated in body-building, and in assisting therapies of metabolic syndromes. It has recently been established that the amelioration of gout by dairy products arises from the competition of orotate and urate at the hURAT1 transporter. The orotic aciduria that arises in children with defective UMP synthase can be rescued by oral uridine therapy, since UMP is the end-product and also a feedback inhibitor of the de novo pathway. In contrast, Miller (dysmorphology) syndrome is connected with defects in DHODH, and hence in the supply of OA, and cannot be helped by uridine. Other models of dysmorphisms are connected with enzymes early in the pyrimidine de novo pathway. We conclude that the OA molecule is itself required for the regulation of genes that are important in the development of cells, tissues and organisms.
[Mh] Termos MeSH primário: Ácido Orótico/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Anticolesterolemiantes/uso terapêutico
Dieta
Seres Humanos
Ácido Orótico/farmacologia
Ácido Orótico/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 61H4T033E5 (Orotic Acid)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170317
[Lr] Data última revisão:
170317
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE


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Texto completo
[PMID]:27650727
[Au] Autor:Tiwari K; Kumar R; Dubey VK
[Ad] Endereço:Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India.
[Ti] Título:Biochemical characterization of dihydroorotase of Leishmania donovani: Understanding pyrimidine metabolism through its inhibition.
[So] Source:Biochimie;131:45-53, 2016 Dec.
[Is] ISSN:1638-6183
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:De novo pyrimidine biosynthesis pathway is well developed and functional in protozoan parasite Leishmania donovani. The dihydroorotase (LdDHOase) is third enzyme of the pathway. The enzyme was cloned, expressed in E. coli BL21 (DE3), purified to homogeneity and biochemically characterized. The estimated kcat for the forward reaction and reverse reactions were 2.1 ± 0.1 s and 1.1 ± 0.15 s , respectively. Homology modeling and docking studies were done to find out potential inhibitors for LdDHOase. Biotin sulfone and Kaempferol were found to be potential inhibitors of LdDHOase based on docking studies. These inhibitors were verified using recombinant LdDHOase and their anti-leishmanial effect was evaluated. Moreover, alterations in expressions of de novo as well as salvage pathways enzymes, after treatment of L. donovani with dihydroorotase inhibitor(s) were evaluated and discussed as survival mechanism of the pathogen. Further, effect of inhibition of cytidine deaminase, a key enzyme of salvage pathway of pyrimidine biosynthesis, was also evaluated on parasitic survival and alteration in gene expression of enzymes of both pathways. Further, effect of both pathways inhibition was also evaluated. The data suggests that the inhibition of single pathway can be overcome by increased expression of enzyme(s) of alternate pathway and both pathways seem to be equally important in the pathogen. When both pathways are simultaneously inhibited, parasite shows significant DNA damage and parasitic death.
[Mh] Termos MeSH primário: Di-Hidro-Orotase/metabolismo
Leishmania donovani/metabolismo
Proteínas de Protozoários/metabolismo
Pirimidinas/metabolismo
[Mh] Termos MeSH secundário: Biotina/análogos & derivados
Biotina/química
Biotina/farmacologia
Citidina Desaminase/antagonistas & inibidores
Citidina Desaminase/genética
Citidina Desaminase/metabolismo
Di-Hidro-Orotase/antagonistas & inibidores
Di-Hidro-Orotase/genética
Eletroforese em Gel de Poliacrilamida
Escherichia coli/genética
Regulação Enzimológica da Expressão Gênica
Quempferóis/química
Quempferóis/farmacologia
Cinética
Leishmania donovani/efeitos dos fármacos
Leishmania donovani/genética
Simulação de Acoplamento Molecular
Estrutura Molecular
Ácido Orótico/análogos & derivados
Ácido Orótico/química
Ácido Orótico/metabolismo
Domínios Proteicos
Proteínas de Protozoários/antagonistas & inibidores
Proteínas de Protozoários/genética
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Especificidade por Substrato
Sulfonas/química
Sulfonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Kaempferols); 0 (Protozoan Proteins); 0 (Pyrimidines); 0 (Recombinant Proteins); 0 (Sulfones); 155-54-4 (4,5-dihydroorotic acid); 22451MYQ9X (biotin sulfone); 61H4T033E5 (Orotic Acid); 6SO6U10H04 (Biotin); 731P2LE49E (kaempferol); EC 3.5.2.3 (Dihydroorotase); EC 3.5.4.5 (Cytidine Deaminase); K8CXK5Q32L (pyrimidine)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160922
[St] Status:MEDLINE



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