Base de dados : MEDLINE
Pesquisa : D08.811.913.555.400.500 [Categoria DeCS]
Referências encontradas : 703 [refinar]
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  1 / 703 MEDLINE  
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[PMID]:29339156
[Au] Autor:Zhang M; Wu W; Chen Z
[Ad] Endereço:Beijing Advanced Innovation Center for Food Nutrition and Human Health, State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
[Ti] Título:Structure and function of cytoplasmic serine hydroxymethyltransferase from Pichia pastoris.
[So] Source:Biochem Biophys Res Commun;496(2):753-757, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Serine hydroxymethyltransferase (SHMT) catalyzes the interconversion of serine and glycine, which is crucial for one carbon metabolism. Here, we report the first crystal structure of cytoplasmic SHMT from Pichia pastoris (pcSHMT) diffracted to 2.5 Šresolution in space group C222 . PcSHMT was a contaminant with our target protein expressed in Pichia pastoris and confirmed by mass spectrometry. The overall structure of pcSHMT is similar to Human mitochondrial SHMT and different to E. coli SHMT. Interestingly, the oligomerization of pcSHMT expressed in eukaryotic or prokaryotic system differs significantly and is regulated by pyridoxal-5'-phosphate. Our results revealed a close evolutionary relationship between Pichia pastoris and Human mitochondria.
[Mh] Termos MeSH primário: Glicina Hidroximetiltransferase/metabolismo
Pichia/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Cristalografia por Raios X
Glicina Hidroximetiltransferase/química
Seres Humanos
Modelos Moleculares
Pichia/química
Pichia/citologia
Pichia/metabolismo
Conformação Proteica
Multimerização Proteica
Fosfato de Piridoxal/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
5V5IOJ8338 (Pyridoxal Phosphate); EC 2.1.2.1 (Glycine Hydroxymethyltransferase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  2 / 703 MEDLINE  
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[PMID]:28760597
[Au] Autor:Amornwatcharapong W; Maenpuen S; Chitnumsub P; Leartsakulpanich U; Chaiyen P
[Ad] Endereço:Department of Biochemistry and Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
[Ti] Título:Human and Plasmodium serine hydroxymethyltransferases differ in rate-limiting steps and pH-dependent substrate inhibition behavior.
[So] Source:Arch Biochem Biophys;630:91-100, 2017 Sep 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Serine hydroxymethyltransferase (SHMT), an essential enzyme for cell growth and development, catalyzes the transfer of -CH OH from l-serine to tetrahydrofolate (THF) to form glycine and 5,10-methylenetetrahydrofolate (MTHF) which is used for nucleotide synthesis. Insights into the ligand binding and inhibition properties of human cytosolic SHMT (hcSHMT) and Plasmodium SHMT (PvSHMT) are crucial for designing specific drugs against malaria and cancer. The results presented here revealed strong and pH-dependent THF inhibition of hcSHMT. In contrast, in PvSHMT, THF inhibition and the influence of pH were not as pronounced. Ligand binding experiments performed at various pH values indicated that the hcSHMT:Gly complex binds THF more tightly at lower pH conditions, while the binding affinity of the PvSHMT:Gly complex for THF is not pH-dependent. Pre-steady state kinetic (rapid-quench) analysis of hcSHMT showed burst kinetics, indicating that glycine formation occurs fastest in the first turnover relative to the subsequent turnovers i.e. glycine release is the rate-limiting step in the hcSHMT reaction. All data suggest that excess THF likely binds E:Gly binary complex and forms the E:Gly:THF dead-end complex before glycine is released. A unique flap motif found in the structure of hcSHMT may be the key structural feature that imparts these described characteristics of hcSHMT.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/química
Glicina Hidroximetiltransferase/antagonistas & inibidores
Glicina Hidroximetiltransferase/química
Plasmodium falciparum/enzimologia
Plasmodium vivax/enzimologia
Proteínas de Protozoários/antagonistas & inibidores
Proteínas de Protozoários/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Seres Humanos
Concentração de Íons de Hidrogênio
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Protozoan Proteins); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 2.1.2.1 (SHMT protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE


  3 / 703 MEDLINE  
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[PMID]:28537728
[Au] Autor:Schwertz G; Witschel MC; Rottmann M; Bonnert R; Leartsakulpanich U; Chitnumsub P; Jaruwat A; Ittarat W; Schäfer A; Aponte RA; Charman SA; White KL; Kundu A; Sadhukhan S; Lloyd M; Freiberg GM; Srikumaran M; Siggel M; Zwyssig A; Chaiyen P; Diederich F
[Ad] Endereço:Laboratorium für Organische Chemie, ETH Zurich , Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland.
[Ti] Título:Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures.
[So] Source:J Med Chem;60(12):4840-4860, 2017 Jun 22.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 Å resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Glicina Hidroximetiltransferase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antimaláricos/química
Proteínas de Arabidopsis/antagonistas & inibidores
Técnicas de Química Sintética
Cristalografia por Raios X
Cisteína/química
Estabilidade de Medicamentos
Inibidores Enzimáticos/metabolismo
Glicina Hidroximetiltransferase/metabolismo
Meia-Vida
Ligantes
Malária Falciparum/tratamento farmacológico
Camundongos SCID
Plasmodium falciparum/efeitos dos fármacos
Plasmodium falciparum/enzimologia
Plasmodium falciparum/patogenicidade
Plasmodium vivax/enzimologia
Conformação Proteica
Ratos
Relação Estrutura-Atividade
Tiofenos/síntese química
Tiofenos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Arabidopsis Proteins); 0 (Enzyme Inhibitors); 0 (Ligands); 0 (Thiophenes); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00008


  4 / 703 MEDLINE  
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[PMID]:28288142
[Au] Autor:Gupta R; Yang Q; Dogra SK; Wajapeyee N
[Ad] Endereço:Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
[Ti] Título:Serine hydroxymethyl transferase 1 stimulates pro-oncogenic cytokine expression through sialic acid to promote ovarian cancer tumor growth and progression.
[So] Source:Oncogene;36(28):4014-4024, 2017 Jul 13.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:High-grade serous (HGS) ovarian cancer accounts for 90% of all ovarian cancer-related deaths. However, factors that drive HGS ovarian cancer tumor growth have not been fully elucidated. In particular, comprehensive analysis of the metabolic requirements of ovarian cancer tumor growth has not been performed. By analyzing The Cancer Genome Atlas mRNA expression data for HGS ovarian cancer patient samples, we observed that six enzymes of the folic acid metabolic pathway were overexpressed in HGS ovarian cancer samples compared with normal ovary samples. Systematic knockdown of all six genes using short hairpin RNAs (shRNAs) and follow-up functional studies demonstrated that serine hydroxymethyl transferase 1 (SHMT1) was necessary for ovarian cancer tumor growth and cell migration in culture and tumor formation in mice. SHMT1 promoter analysis identified transcription factor Wilms tumor 1 (WT1) binding sites, and WT1 knockdown resulted in reduced SHMT1 transcription in ovarian cancer cells. Unbiased large-scale metabolomic analysis and transcriptome-wide mRNA expression profiling identified reduced levels of several metabolites of the amino sugar and nucleotide sugar metabolic pathways, including sialic acid N-acetylneuraminic acid (Neu5Ac), and downregulation of pro-oncogenic cytokines interleukin-6 and 8 (IL-6 and IL-8) as unexpected outcomes of SHMT1 loss. Overexpression of either IL-6 or IL-8 partially rescued SHMT1 loss-induced tumor growth inhibition and migration. Supplementation of culture medium with Neu5Ac stimulated expression of IL-6 and IL-8 and rescued the tumor growth and migratory phenotypes of ovarian cancer cells expressing SHMT1 shRNAs. In agreement with the ovarian tumor-promoting role of Neu5Ac, treatment with Neu5Ac-targeting glycomimetic P-3Fax-Neu5Ac blocked ovarian cancer growth and migration. Collectively, these results demonstrate that SHMT1 controls the expression of pro-oncogenic inflammatory cytokines by regulating sialic acid Neu5Ac to promote ovarian cancer tumor growth and migration. Thus, targeting of SHMT1 and Neu5Ac represents a precision therapy opportunity for effective HGS ovarian cancer treatment.
[Mh] Termos MeSH primário: Carcinogênese/genética
Proliferação Celular/genética
Cistadenocarcinoma Seroso/patologia
Citocinas/genética
Glicina Hidroximetiltransferase/fisiologia
Ácido N-Acetilneuramínico/metabolismo
Neoplasias Ovarianas/patologia
[Mh] Termos MeSH secundário: Animais
Carcinogênese/metabolismo
Carcinogênese/patologia
Linhagem Celular Tumoral
Cistadenocarcinoma Seroso/genética
Cistadenocarcinoma Seroso/metabolismo
Citocinas/metabolismo
Progressão da Doença
Feminino
Regulação Neoplásica da Expressão Gênica
Células HEK293
Seres Humanos
Mediadores da Inflamação/metabolismo
Camundongos
Camundongos Nus
Neoplasias Ovarianas/genética
Neoplasias Ovarianas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Inflammation Mediators); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 2.1.2.1 (SHMT protein, human); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170314
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.37


  5 / 703 MEDLINE  
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[PMID]:28259896
[Au] Autor:Konno M; Asai A; Kawamoto K; Nishida N; Satoh T; Doki Y; Mori M; Ishii H
[Ad] Endereço:Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka 565-0871, Japan.
[Ti] Título:The one-carbon metabolism pathway highlights therapeutic targets for gastrointestinal cancer (Review).
[So] Source:Int J Oncol;50(4):1057-1063, 2017 Apr.
[Is] ISSN:1791-2423
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:After the initial use of anti-folates for treatment of malignancies, folate metabolism has emerged as a rational diagnostic and therapeutic target in gastrointestinal cancer. The one-carbon metabolic pathway, which comprises three critical reactions (i.e., folate and methionine cycles), underlies this effect in conjunction with the trans-sulfuration pathway. Understanding of the one-carbon metabolism pathway has served to unravel the link between the causes and effects of cancer phenotypes leading to several seminal discoveries such as that of diadenosine tri-phosphate hydrolase, microRNAs, 5-FU and, more recently, trifluridine. In the folate cycle, glycine and serine fuel the mitochondrial enzymes SHMT2, MTHFD2 and ALDH1L2, which play critical roles in the cancer survival and proliferation presumably through purine production. In the methionine cycle, S-adenocyl methionine serves hydrocarbons and polyamines that are critical for the epigenetic controls. The trans-sulfuration pathway is a critical component in the synthesis of glutathione, which is involved in the production of reactive oxygen species in cancer stem cells. Therefore, characterization of one-carbon metabolism is indispensable to the development of precision medicine in the context of cancer diagnostics and therapeutics. In the present study, we review the historical issues associated with one-carbon metabolism and highlight the recent advances in cancer research.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Ácido Fólico/metabolismo
Neoplasias Gastrointestinais/metabolismo
Redes e Vias Metabólicas/efeitos dos fármacos
Metionina/metabolismo
Mitocôndrias/metabolismo
Terapia de Alvo Molecular/métodos
[Mh] Termos MeSH secundário: Aminoidrolases/metabolismo
Fluoruracila/metabolismo
Antagonistas do Ácido Fólico/uso terapêutico
Neoplasias Gastrointestinais/tratamento farmacológico
Glicina Hidroximetiltransferase/metabolismo
Seres Humanos
Metaboloma
Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo
MicroRNAs/metabolismo
Mitocôndrias/enzimologia
Complexos Multienzimáticos/metabolismo
Nucleosídeos/uso terapêutico
Nucleotídeos/uso terapêutico
Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo
Purinas/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Serina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Folic Acid Antagonists); 0 (MicroRNAs); 0 (Multienzyme Complexes); 0 (Nucleosides); 0 (Nucleotides); 0 (Purines); 0 (Reactive Oxygen Species); 0 (methylene tetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase); 452VLY9402 (Serine); 935E97BOY8 (Folic Acid); AE28F7PNPL (Methionine); EC 1.5.- (ALDH1L2 protein, human); EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors); EC 1.5.1.5 (Methylenetetrahydrofolate Dehydrogenase (NADP)); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 2.1.2.1 (SHMT protein, human); EC 3.5.4.- (Aminohydrolases); U3P01618RT (Fluorouracil); W60KTZ3IZY (purine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170306
[St] Status:MEDLINE
[do] DOI:10.3892/ijo.2017.3885


  6 / 703 MEDLINE  
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[PMID]:28107674
[Au] Autor:Wang B; Wang W; Zhu Z; Zhang X; Tang F; Wang D; Liu X; Yan X; Zhuang H
[Ad] Endereço:Department of Neurosurgery, Tianjin HuanHu Hospital, Tianjin Key Laboratory of Cerebrovascular Disease and Neurodegenerative Disease, Tianjin Neurosurgical Institute, 6 Jizhao Road, Tianjin, China.
[Ti] Título:Mitochondrial serine hydroxymethyltransferase 2 is a potential diagnostic and prognostic biomarker for human glioma.
[So] Source:Clin Neurol Neurosurg;154:28-33, 2017 Mar.
[Is] ISSN:1872-6968
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Scholars have gradually come to appreciate the relevance of serine and glycine metabolism. Recently, researchers have discovered that mitochondrial serine hydroxymethyltransferase 2 (SHMT2) is overexpressed in various types of cancer. However, the function of SHMT2 in glioma is not clear. In this study, we sought to examine the expression of SHMT2 in glioma, the association between SHMT2 expression and clinicopathological characteristics, and the association of SHMT2 expression with prognosis in glioma patients. METHODS: We evaluated the expression of SHMT2, Ki67, O-6-methylguanine-DNA methyltransferase (MGMT), and Glutathione S Transferase pi (GST-pi) in 150 glioma patients using immunohistochemistry assays. The associations among the expression of SHMT2, clinicopathological parameters, and outcome of glioma patients were statistically analysed. RESULTS: The expression of SHMT2 was increased in gliomas compared to normal brain tissue and gradually increased with increasing WHO grade. The SHMT2 expression was positively correlated with Ki67 expression and WHO degree (p<0.01) but was not correlated with other clinicopathological parameters, including sex, age, Karnofsky Performance Status (KPS), tumour diameter, MGMT, and GST-pi (p>0.05). Kaplan-Meier survival curves and Cox regression analyses showed that SHMT2 expression and the WHO grade were independent prognostic indicators for glioma patients. CONCLUSION: The expression of SHMT2 in glioma was significantly increased compared to normal brain tissue. SHMT2 promoted tumour proliferation, and there was no association between SHMT2 and drug resistance mechanisms of glioma. SHMT2 may be a novel and valuable biomarker for the diagnosis of glioma and an independent prognostic parameter of glioma.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Neoplasias Encefálicas/metabolismo
Glioma/metabolismo
Glicina Hidroximetiltransferase/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Prognóstico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 2.1.2.1 (SHMT protein, human)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170322
[Lr] Data última revisão:
170322
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE


  7 / 703 MEDLINE  
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[PMID]:28038776
[Au] Autor:Hirato Y; Tokuhisa M; Tanigawa M; Ashida H; Tanaka H; Nishimura K
[Ad] Endereço:Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, 1-8-14 Kanda-Surugadai, Chiyoda-Ku, Tokyo, 101-8308, Japan.
[Ti] Título:Cloning and characterization of d-threonine aldolase from the green alga Chlamydomonas reinhardtii.
[So] Source:Phytochemistry;135:18-23, 2017 Mar.
[Is] ISSN:1873-3700
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:d-Threonine aldolase (DTA) catalyzes the pyridoxal 5'-phosphate (PLP)-dependent interconversion of d-threonine and glycine plus acetaldehyde. The enzyme is a powerful tool for the stereospecific synthesis of various ß-hydroxy amino acids in synthetic organic chemistry. In this study, DTA from the green alga Chlamydomonas reinhardtii was discovered and characterized, representing the first report to describe the existence of eukaryotic DTA. DTA was overexpressed in recombinant Escherichia coli BL21 (DE3) cells; the specific activity of the enzyme in the cell-free extract was 0.8 U/mg. The recombinant enzyme was purified to homogeneity by ammonium sulfate fractionation, DEAE-Sepharose, and Mono Q column chromatographies (purified enzyme 7.0 U/mg). For the cleavage reaction, the optimal temperature and pH were 70 °C and pH 8.4, respectively. The enzyme demonstrated 90% of residual activity at 50 °C for 1 h. The enzyme catalyzed the synthesis of d- and d-allo threonine from a mixture of glycine and acetaldehyde (the diastereomer excess of d-threonine was 18%). DTA was activated by several divalent metal ions, including manganese, and was inhibited by PLP enzyme inhibitors and metalloenzyme inhibitors.
[Mh] Termos MeSH primário: Chlamydomonas reinhardtii/metabolismo
Glicina Hidroximetiltransferase/metabolismo
[Mh] Termos MeSH secundário: Aldeído Liases/metabolismo
Sequência de Aminoácidos
Chlamydomonas reinhardtii/enzimologia
Clonagem Molecular
Escherichia coli/genética
Glicina/metabolismo
Fosfato de Piridoxal/metabolismo
Estereoisomerismo
Especificidade por Substrato
Treonina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
2ZD004190S (Threonine); 5V5IOJ8338 (Pyridoxal Phosphate); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 4.1.2.- (Aldehyde-Lyases); EC 4.1.2.5 (threonine acetaldehyde-lyase); TE7660XO1C (Glycine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170316
[Lr] Data última revisão:
170316
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170101
[St] Status:MEDLINE


  8 / 703 MEDLINE  
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[PMID]:27659940
[Au] Autor:Jiang YC; Kuang LL; Sun SN; Duan WY; Qiao B; Wang HY
[Ad] Endereço:State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University.
[Ti] Título:Association of genetic polymorphisms of de novo nucleotide biosynthesis with increased CHD susceptibility in the northern Chinese population.
[So] Source:Clin Genet;91(5):748-755, 2017 May.
[Is] ISSN:1399-0004
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:Congenital heart disease (CHD) is one of most prevalent birth defects in the world. However, the underlying molecular mechanism(s) have not been fully understood. Here we report that increased CHD susceptibility is associated with genetic polymorphisms for de novo nucleotide biosynthesis in northern Chinese population, which has been reported with lower plasma folate levels. Nine tagSNPs of four genes (GART, ATIC, MTHFD1 and SHMT1) in de novo nucleotide biosynthesis were sequenced in 802 sporadic CHD patients and 1093 controls from two Han Chinese populations, located in north China (Shandong) and South China (Shanghai), respectively. Six SNPs were found to be significantly associated with CHDs or septation defects only in the Shandong population dataset, but none displayed significant association with any CHDs in the Shanghai population dataset as well as in the combined dataset. We also showed that the minor A allele of rs7279549 in GART reduced transcriptional activity and displayed lower affinity for unknown transcription factor(s), demonstrating the allele is a functional risk factor for CHD in Shandong population. Our study indicates that dysregulation of de novo nucleotide biosynthesis pathway may conditionally contribute to CHD pathogenesis in northern Chinese.
[Mh] Termos MeSH primário: Carbono-Nitrogênio Ligases/genética
Glicina Hidroximetiltransferase/genética
Cardiopatias Congênitas/genética
Hidroximetil e Formil Transferases/genética
Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética
Antígenos de Histocompatibilidade Menor/genética
Complexos Multienzimáticos/genética
Nucleotídeo Desaminases/genética
Fosforribosilglicinamido Formiltransferase/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Alelos
Grupo com Ancestrais do Continente Asiático/genética
Estudos de Casos e Controles
Predisposição Genética para Doença
Seres Humanos
Nucleotídeos/biossíntese
Nucleotídeos/genética
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Minor Histocompatibility Antigens); 0 (Multienzyme Complexes); 0 (Nucleotides); 0 (Transcription Factors); 0 (inosine monophosphate synthase); EC 1.5.1.5 (MTHFD1 protein, human); EC 1.5.1.5 (Methylenetetrahydrofolate Dehydrogenase (NADP)); EC 2.1.2.- (Hydroxymethyl and Formyl Transferases); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 2.1.2.1 (SHMT protein, human); EC 2.1.2.2 (Phosphoribosylglycinamide Formyltransferase); EC 3.5.4.- (Nucleotide Deaminases); EC 6.3.- (Carbon-Nitrogen Ligases); EC 6.3.4.13 (GART protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170602
[Lr] Data última revisão:
170602
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160924
[St] Status:MEDLINE
[do] DOI:10.1111/cge.12874


  9 / 703 MEDLINE  
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[PMID]:27443667
[Au] Autor:Waditee-Sirisattha R; Kageyama H; Tanaka Y; Fukaya M; Takabe T
[Ad] Endereço:Research Institute of Meijo University, Nagoya, 468-8502, Japan.
[Ti] Título:Overexpression of halophilic serine hydroxymethyltransferase in fresh water cyanobacterium Synechococcus elongatus PCC7942 results in increased enzyme activities of serine biosynthetic pathways and enhanced salinity tolerance.
[So] Source:Arch Microbiol;199(1):29-35, 2017 Jan.
[Is] ISSN:1432-072X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Serine hydroxymethyltransferase (SHMT) catalyzes the conversion of serine to glycine and provides activated one-carbon units required for synthesis of nucleic acids, proteins and numerous biological compounds. SHMT is involved in photorespiratory pathway of oxygenic photosynthetic organisms. Accumulating evidence revealed that SHMT plays vital role for abiotic stresses such as low CO and high salinity in plants, but its role in cyanobacteria remains to be clarified. In this study, we examined to overexpress the SHMT from halotolerant cyanobacterium Aphanothece halophytica in freshwater cyanobacterium, Synechococcus elongatus PCC7942. The transformed cells did not show an obvious phenotype under non-stress condition, but exhibited more tolerance to salinity than the control cells harboring vector only under high salinity. Elevated levels of enzymes in phosphorylated serine biosynthetic pathway and photorespiration pathway were observed in the transformed cells. Glycine level was also increased in the transformed cells. Physiological roles of SHMT for salt tolerance were discussed.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Vias Biossintéticas
Glicina Hidroximetiltransferase/genética
Serina/biossíntese
Synechococcus/genética
[Mh] Termos MeSH secundário: Proteínas de Bactérias/metabolismo
Água Doce/microbiologia
Glicina Hidroximetiltransferase/metabolismo
Fotossíntese
Tolerância a Sal
Synechococcus/enzimologia
Synechococcus/isolamento & purificação
Synechococcus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 452VLY9402 (Serine); EC 2.1.2.1 (Glycine Hydroxymethyltransferase)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160723
[St] Status:MEDLINE
[do] DOI:10.1007/s00203-016-1271-z


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[PMID]:27973419
[Au] Autor:Troesch B; Weber P; Mohajeri MH
[Ad] Endereço:DSM Nutritional Products Ltd., Wurmisweg 576, Kaiseraugst 4303, Switzerland. barbara.troesch@dsm.com.
[Ti] Título:Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer's Disease.
[So] Source:Nutrients;8(12), 2016 Dec 10.
[Is] ISSN:2072-6643
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Alzheimer's disease (AD) is the major cause of dementia and no preventive or effective treatment has been established to date. The etiology of AD is poorly understood, but genetic and environmental factors seem to play a role in its onset and progression. In particular, factors affecting the one-carbon metabolism (OCM) are thought to be important and elevated homocysteine (Hcy) levels, indicating impaired OCM, have been associated with AD. We aimed at evaluating the role of polymorphisms of key OCM enzymes in the etiology of AD, particularly when intakes of relevant B-vitamins are inadequate. Our review indicates that a range of compensatory mechanisms exist to maintain a metabolic balance. However, these become overwhelmed if the activity of more than one enzyme is reduced due to genetic factors or insufficient folate, riboflavin, vitamin B6 and/or vitamin B12 levels. Consequences include increased Hcy levels and reduced capacity to synthetize, methylate and repair DNA, and/or modulated neurotransmission. This seems to favor the development of hallmarks of AD particularly when combined with increased oxidative stress e.g., in apolipoprotein E (ApoE) ε4 carriers. However, as these effects can be compensated at least partially by adequate intakes of B-vitamins, achieving optimal B-vitamin status for the general population should be a public health priority.
[Mh] Termos MeSH primário: Doença de Alzheimer/etiologia
Medicina Baseada em Evidências
Hiper-Homocisteinemia/fisiopatologia
Metionina/metabolismo
Modelos Biológicos
Polimorfismo Genético
Deficiência de Vitaminas do Complexo B/fisiopatologia
[Mh] Termos MeSH secundário: 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo
Doença de Alzheimer/genética
Doença de Alzheimer/metabolismo
Doença de Alzheimer/prevenção & controle
Animais
Cistationina beta-Sintase/genética
Cistationina beta-Sintase/metabolismo
Ferredoxina-NADP Redutase/genética
Ferredoxina-NADP Redutase/metabolismo
Predisposição Genética para Doença
Glicina Hidroximetiltransferase/genética
Glicina Hidroximetiltransferase/metabolismo
Seres Humanos
Hiper-Homocisteinemia/genética
Hiper-Homocisteinemia/metabolismo
Hiper-Homocisteinemia/prevenção & controle
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética
Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo
Mutagênese Insercional
Nutrigenômica/métodos
Nutrigenômica/tendências
Estado Nutricional
Polimorfismo de Nucleotídeo Único
Sequências de Repetição em Tandem
Complexo Vitamínico B/metabolismo
Complexo Vitamínico B/uso terapêutico
Deficiência de Vitaminas do Complexo B/dietoterapia
Deficiência de Vitaminas do Complexo B/metabolismo
Deficiência de Vitaminas do Complexo B/prevenção & controle
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
12001-76-2 (Vitamin B Complex); AE28F7PNPL (Methionine); EC 1.18.1.- (methionine synthase reductase); EC 1.18.1.2 (Ferredoxin-NADP Reductase); EC 1.5.1.20 (MTHFR protein, human); EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2)); EC 2.1.1.13 (5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase); EC 2.1.1.13. (MTR protein, human); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 2.1.2.1 (SHMT protein, human); EC 4.2.1.22 (Cystathionine beta-Synthase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170331
[Lr] Data última revisão:
170331
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE



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