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[PMID]:29235834
[Au] Autor:Holota YV; Olefir YA; Dovbynchuk TV; Tolstanova GM
[Ti] Título:Carbohydrate composition of rat intestine surface mucus layer after ceftriaxone treatment.
[So] Source:Ukr Biochem J;88(6):35-44, 2016 Nov-Dec.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The epidemiological studies have shown that antibiotic treatment increases the susceptibility to inflammatory bowel disease development. The disturbance of mucus layer integrity might be one of the possible mechanisms. The aim of the present study was to investigate the effect of antibiotic ceftriaxone treatment on glycoproteins level and its carbohydrate composition in surface mucus layer of rat intestine. The study was done on male Wistar rats (140-160 g). Ceftriaxone (300 mg/kg, i.m.) was administered once a day for 14 days. The surface mucus from terminal ileum and colon were collected on the 15th, 29th and 72nd days of the experiment. Total level of mucus glycoproteins, hexoses, hexosamines, fucose and sialic acids were measured. Ceftriaxone administration did not affect the levels of glycoproteins in rat ileum. In the colon, the levels of glycoprotein were 1.3-fold decreased (Р < 0.05) on the 72nd day of the experiment. These changes were accompanied by the 1.2-fold decrease of hexoses (Р < 0.05) and 3.1-fold (Р < 0.05) decrease of fucose level and 1.5-fold (Р < 0.05) increase of the levels of sialic acids in the surface mucus of the rat colon. Thus, ceftriaxone administration induces the long-term changes in the levels of glycoproteins and carbohydrates composition in the rat colon surface mucus. This could potentially explain the susceptibility to inflammatory bowel disea­ses development.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Ceftriaxona/farmacologia
Colo/efeitos dos fármacos
Íleo/efeitos dos fármacos
Muco/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Colo/química
Colo/metabolismo
Esquema de Medicação
Fucose/metabolismo
Glicoproteínas/metabolismo
Hexosaminas/metabolismo
Hexoses/metabolismo
Íleo/química
Íleo/metabolismo
Injeções Intramusculares
Masculino
Muco/química
Muco/metabolismo
Ratos
Ratos Wistar
Ácidos Siálicos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycoproteins); 0 (Hexosamines); 0 (Hexoses); 0 (Sialic Acids); 28RYY2IV3F (Fucose); 75J73V1629 (Ceftriaxone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.06.035


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[PMID]:28706006
[Au] Autor:Gibb AA; Lorkiewicz PK; Zheng YT; Zhang X; Bhatnagar A; Jones SP; Hill BG
[Ad] Endereço:Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40202, U.S.A.
[Ti] Título:Integration of flux measurements to resolve changes in anabolic and catabolic metabolism in cardiac myocytes.
[So] Source:Biochem J;474(16):2785-2801, 2017 Aug 07.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although ancillary pathways of glucose metabolism are critical for synthesizing cellular building blocks and modulating stress responses, how they are regulated remains unclear. In the present study, we used radiometric glycolysis assays, [ C ]-glucose isotope tracing, and extracellular flux analysis to understand how phosphofructokinase (PFK)-mediated changes in glycolysis regulate glucose carbon partitioning into catabolic and anabolic pathways. Expression of kinase-deficient or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat neonatal cardiomyocytes co-ordinately regulated glycolytic rate and lactate production. Nevertheless, in all groups, >40% of glucose consumed by the cells was unaccounted for via catabolism to pyruvate, which suggests entry of glucose carbons into ancillary pathways branching from metabolites formed in the preparatory phase of glycolysis. Analysis of C fractional enrichment patterns suggests that PFK activity regulates glucose carbon incorporation directly into the ribose and the glycerol moieties of purines and phospholipids, respectively. Pyrimidines, UDP- -acetylhexosamine, and the fatty acyl chains of phosphatidylinositol and triglycerides showed lower C incorporation under conditions of high PFK activity; the isotopologue C enrichment pattern of each metabolite indicated limitations in mitochondria-engendered aspartate, acetyl CoA and fatty acids. Consistent with this notion, high glycolytic rate diminished mitochondrial activity and the coupling of glycolysis to glucose oxidation. These findings suggest that a major portion of intracellular glucose in cardiac myocytes is apportioned for ancillary biosynthetic reactions and that PFK co-ordinates the activities of the pentose phosphate, hexosamine biosynthetic, and glycerolipid synthesis pathways by directly modulating glycolytic intermediate entry into auxiliary glucose metabolism pathways and by indirectly regulating mitochondrial cataplerosis.
[Mh] Termos MeSH primário: Glucose/metabolismo
Glicólise
Mitocôndrias Musculares/metabolismo
Miócitos Cardíacos/metabolismo
Via de Pentose Fosfato
Fosfofrutoquinase-1 Hepática/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Animais Recém-Nascidos
Isótopos de Carbono
Células Cultivadas
Meios de Cultura Livres de Soro
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Hexosaminas/metabolismo
Ácido Láctico/metabolismo
Mitocôndrias Musculares/enzimologia
Miócitos Cardíacos/citologia
Miócitos Cardíacos/enzimologia
Oligopeptídeos/genética
Oligopeptídeos/metabolismo
Fosfofrutoquinase-1 Hepática/genética
Mutação Puntual
Pirimidinas/metabolismo
Ácido Pirúvico/metabolismo
Ratos Sprague-Dawley
Proteínas Recombinantes de Fusão/metabolismo
Difosfato de Uridina/análogos & derivados
Difosfato de Uridina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbon Isotopes); 0 (Culture Media, Serum-Free); 0 (Hexosamines); 0 (Oligopeptides); 0 (Pyrimidines); 0 (Recombinant Fusion Proteins); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); 33X04XA5AT (Lactic Acid); 58-98-0 (Uridine Diphosphate); 8558G7RUTR (Pyruvic Acid); 98849-88-8 (FLAG peptide); EC 2.7.1.- (Phosphofructokinase-1, Liver Type); EC 2.7.1.- (phosphofructokinase-1 subunit, type L); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171007
[Lr] Data última revisão:
171007
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170474


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[PMID]:28636341
[Au] Autor:Riegert AS; Chantigian DP; Thoden JB; Tipton PA; Holden HM
[Ad] Endereço:Department of Biochemistry, University of Wisconsin , Madison, Wisconsin 53706, United States.
[Ti] Título:Biochemical Characterization of WbkC, an N-Formyltransferase from Brucella melitensis.
[So] Source:Biochemistry;56(28):3657-3668, 2017 Jul 18.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It has become increasingly apparent within the last several years that unusual N-formylated sugars are often found on the O-antigens of such Gram negative pathogenic organisms as Francisella tularensis, Campylobacter jejuni, and Providencia alcalifaciens, among others. Indeed, in some species of Brucella, for example, the O-antigen contains 1,2-linked 4-formamido-4,6-dideoxy-α-d-mannosyl groups. These sugars, often referred to as N-formylperosamine, are synthesized in pathways initiating with GDP-mannose. One of the enzymes required for the production of N-formylperosamine, namely, WbkC, was first identified in 2000 and was suggested to function as an N-formyltransferase. Its biochemical activity was never experimentally verified, however. Here we describe a combined structural and functional investigation of WbkC from Brucella melitensis. Four high resolution X-ray structures of WbkC were determined in various complexes to address its active site architecture. Unexpectedly, the quaternary structure of WbkC was shown to be different from that previously observed for other sugar N-formyltransferases. Additionally, the structures revealed a second binding site for a GDP molecule distinct from that required for GDP-perosamine positioning. In keeping with this additional binding site, kinetic data with the wild type enzyme revealed complex patterns. Removal of GDP binding by mutating Phe 142 to an alanine residue resulted in an enzyme variant displaying normal Michaelis-Menten kinetics. These data suggest that this nucleotide binding pocket plays a role in enzyme regulation. Finally, by using an alternative substrate, we demonstrate that WbkC can be utilized to produce a trideoxysugar not found in nature.
[Mh] Termos MeSH primário: Brucella melitensis/enzimologia
Hidroximetil e Formil Transferases/metabolismo
[Mh] Termos MeSH secundário: Sítios de Ligação
Brucella melitensis/química
Brucelose/microbiologia
Domínio Catalítico
Cristalografia por Raios X
Guanosina Difosfato/metabolismo
Hexosaminas/metabolismo
Seres Humanos
Hidroximetil e Formil Transferases/química
Cinética
Modelos Moleculares
Conformação Proteica
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-formamido-4,6-dideoxymannose); 0 (Hexosamines); 146-91-8 (Guanosine Diphosphate); EC 2.1.2.- (Hydroxymethyl and Formyl Transferases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170806
[Lr] Data última revisão:
170806
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00494


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[PMID]:28599260
[Au] Autor:Matyjaszczyk K; Kolonko M; Gonciarz-Dytman A; Oszczapowicz I; Lukawska M; Jawien W; Chlopicki S; Walczak M
[Ad] Endereço:Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348 Kraków, Poland; Chair and Department of Toxicology, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
[Ti] Título:Effects of structural modification of the daunosamine moiety of anthracycline antibiotics on pK values determined by capillary zone electrophoresis.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1060:44-52, 2017 Aug 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The thermodynamic acid dissociation constants (pK and pK ) of 16 anthracycline antibiotics, including doxorubicin (DOX) and daunorubicin (DAU), their epimers, epidoxorubicin (EDOX) and epidaunorubicin (EDAU), as well as novel anthracycline derivatives containing piperidine (FPIP), morpholine (FMOR) and hexamethylenoimine (FHEX) rings in the formamidine group of the daunosamine moiety were determined by analysis of the dependence between measured electrophoretic mobility and the pH of the buffer using the capillary zone electrophoresis method. The results obtained confirmed the ampholytic character of anthracyclines with at least two ionization states. The determined values were in the range of 8.36-9.28 and 9.38-11.48 for pK and pK arising from ionization of amino and phenolic groups, respectively. Structural modifications in the daunosamine moiety of the studied anthracyclines affected their pharmacological properties, such as antiproliferative activity.
[Mh] Termos MeSH primário: Antraciclinas/química
Antibióticos Antineoplásicos/química
Eletroforese Capilar/métodos
Hexosaminas/química
[Mh] Termos MeSH secundário: Amidinas
Antraciclinas/farmacologia
Antibióticos Antineoplásicos/farmacologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Hexosaminas/farmacologia
Seres Humanos
Concentração de Íons de Hidrogênio
Dinâmica não Linear
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amidines); 0 (Anthracyclines); 0 (Antibiotics, Antineoplastic); 0 (Hexosamines); 26548-47-0 (daunosamine); 463-52-5 (formamidine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE


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[PMID]:28582574
[Au] Autor:Hugo SE; Schlegel A
[Ad] Endereço:University of Utah Molecular Medicine Program, University of Utah School of Medicine, Salt Lake City, Utah 84112.
[Ti] Título:A Genetic Model to Study Increased Hexosamine Biosynthetic Flux.
[So] Source:Endocrinology;158(8):2420-2426, 2017 Aug 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. Larvae showed increased triacylglycerol in the absence of other obvious defects. When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). The mutated protein shows increased abundance. The HBP generates ß-N-acetyl-glucosamine (GlcNAc) as a spillover pathway from glucose. GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. This animal model will provide a platform for dissecting how O-GlcNAc modification alters insulin responsiveness in multiple tissues.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/fisiologia
Hexosaminas/biossíntese
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Configuração de Carboidratos
DNA Complementar
Feminino
Glicosilação
Larva
Masculino
Repetições de Microssatélites
Mutagênese
Conformação Proteica
Peixe-Zebra
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (Hexosamines); 0 (Zebrafish Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00359


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[PMID]:28533470
[Au] Autor:Padra JT; Sundh H; Sundell K; Venkatakrishnan V; Jin C; Samuelsson T; Karlsson NG; Lindén SK
[Ad] Endereço:Department of Medical Chemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
[Ti] Título:Aeromonas salmonicida Growth in Response to Atlantic Salmon Mucins Differs between Epithelial Sites, Is Governed by Sialylated and -Acetylhexosamine-Containing -Glycans, and Is Affected by Ca .
[So] Source:Infect Immun;85(8), 2017 Aug.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:causes furunculosis in salmonids and is a threat to Atlantic salmon aquaculture. The epithelial surfaces that the pathogen colonizes are covered by a mucus layer predominantly comprised of secreted mucins. By using mass spectrometry to identify mucin glycan structures with and without enzymatic removal of glycan residues, coupled to measurements of bacterial growth, we show here that the complex Atlantic salmon intestinal mucin glycans enhance growth, whereas the more simple skin mucin glycans do not. Of the glycan residues present terminally on the salmon mucins, only -acetylglucosamine (GlcNAc) enhances growth. Sialic acids, which have an abundance of 75% among terminal glycans from skin and of <50% among intestinal glycans, cannot be removed or used by for growth-enhancing purposes, and they shield internal GlcNAc from utilization. A Ca concentration above 0.1 mM is needed for to be able to utilize mucins for growth-promoting purposes, and 10 mM further enhances both growth in response to mucins and binding of the bacterium to mucins. In conclusion, GlcNAc and sialic acids are important determinants of the interaction with its host at the mucosal surface. Furthermore, since the mucin glycan repertoire affects pathogen growth, the glycan repertoire may be a factor to take into account during breeding and selection of strains for aquaculture.
[Mh] Termos MeSH primário: Acetilglucosamina/metabolismo
Aeromonas salmonicida/crescimento & desenvolvimento
Cálcio/metabolismo
Mucinas/metabolismo
Polissacarídeos/química
Salmo salar/metabolismo
Ácidos Siálicos/metabolismo
[Mh] Termos MeSH secundário: Aeromonas salmonicida/patogenicidade
Aeromonas salmonicida/fisiologia
Animais
Aquicultura
Furunculose/microbiologia
Glicosilação
Hexosaminas/química
Intestinos/química
Espectrometria de Massas
Mucinas/química
Polissacarídeos/metabolismo
Pele/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hexosamines); 0 (Mucins); 0 (Polysaccharides); 0 (Sialic Acids); SY7Q814VUP (Calcium); V956696549 (Acetylglucosamine)
[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:170524
[St] Status:MEDLINE


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[PMID]:28367638
[Au] Autor:Cui L; Guan XQ; Liu ZM; Fan LY; Li Q; Feng Y
[Ad] Endereço:a State Key Laboratory of Microbial Metabolism, School of Life Science & Biotechnology, and Joint International Research Laboratory of Metabolic & Developmental Sciences , Shanghai Jiao Tong University , Shanghai 200240 , China.
[Ti] Título:A new pre-column derivatization for valienamine and beta-valienamine using o-phthalaldehyde to determine the epimeric purity by HPLC and application of this method to monitor enzymatic catalyzed synthesis of beta-valienamine.
[So] Source:J Asian Nat Prod Res;19(4):347-357, 2017 Apr.
[Is] ISSN:1477-2213
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Valienamine and ß-valienamine are representative C N aminocyclitols with significant glycosidase inhibition activity that have been developed as important precursors of drugs for diabetes and lysosomal storage diseases, respectively. The quantitative analysis of these chiral compounds is crucial for asymmetric in vitro biosynthetic processes for converting valienone into valienamine epimers using aminotransferase. Here, we developed an efficient and sensitive method for separation and quantitative analysis of chiral valienamine using reversed-phase high-performance liquid chromatography (HPLC) through o-phthalaldehyde (OPA) pre-column derivatization of the analytes. The epimers were derivatized by OPA in borate buffer (pH 9.0) at room temperature for 30 s, separated on an Eclipse XDB-C18 (5 µm, 4.6 × 150 mm) column, eluted with 22% acetonitrile at 30 °C for 18 min, and detected by a fluorescence detector using 445 nm emission and 340 nm excitation wavelengths. The average resolution of the epimers is 3.86, and the concentration linearity is in the range of 0.02-20 µg/ml. The method proved to be effective, sensitive, and reliable with good intra- and inter-day precision and accuracy, and successfully evaluated the enantiopreference and catalytic capability of the potential aminotransferases on an unnatural prochiral substrate, facilitating the design of an asymmetric biosynthetic route for optically pure valienamine and ß-valienamine.
[Mh] Termos MeSH primário: Cicloexenos/síntese química
Hexosaminas/síntese química
o-Ftalaldeído/química
[Mh] Termos MeSH secundário: Catálise
Cromatografia Líquida de Alta Pressão/métodos
Cicloexenos/química
Hexosaminas/química
Estrutura Molecular
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclohexenes); 0 (Hexosamines); 38231-86-6 (valienamine); 643-79-8 (o-Phthalaldehyde)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170412
[Lr] Data última revisão:
170412
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1080/10286020.2017.1292257


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[PMID]:28347843
[Au] Autor:Slámová K; Bojarová P
[Ad] Endereço:Laboratory of Biotransformation, Institute of Microbiology, Czech Academy of Sciences, Vídenská 1083, CZ 14220 Prague 4, Czech Republic.
[Ti] Título:Engineered N-acetylhexosamine-active enzymes in glycoscience.
[So] Source:Biochim Biophys Acta;1861(8):2070-2087, 2017 08.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In recent years, enzymes modifying N-acetylhexosamine substrates have emerged in numerous theoretical studies as well as practical applications from biology, biomedicine, and biotechnology. Advanced enzyme engineering techniques converted them into potent synthetic instruments affording a variety of valuable glycosides. SCOPE OF REVIEW: This review presents the diversity of engineered enzymes active with N-acetylhexosamine carbohydrates: from popular glycoside hydrolases and glycosyltransferases to less known oxidases, epimerases, kinases, sulfotransferases, and acetylases. Though hydrolases in natura, engineered chitinases, ß-N-acetylhexosaminidases, and endo-ß-N-acetylglucosaminidases were successfully employed in the synthesis of defined natural and derivatized chitooligomers and in the remodeling of N-glycosylation patterns of therapeutic antibodies. The genes of various N-acetylhexosaminyltransferases were cloned into metabolically engineered microorganisms for producing human milk oligosaccharides, Lewis X structures, and human-like glycoproteins. Moreover, mutant N-acetylhexosamine-active glycosyltransferases were applied, e.g., in the construction of glycomimetics and complex glycostructures, industrial production of low-lactose milk, and metabolic labeling of glycans. In the synthesis of biotechnologically important compounds, several innovative glycoengineered systems are presented for an efficient bioproduction of GlcNAc, UDP-GlcNAc, N-acetylneuraminic acid, and of defined glycosaminoglycans. MAJOR CONCLUSIONS: The above examples demonstrate that engineering of N-acetylhexosamine-active enzymes was able to solve complex issues such as synthesis of tailored human-like glycoproteins or industrial-scale production of desired oligosaccharides. Due to the specific catalytic mechanism, mutagenesis of these catalysts was often realized through rational solutions. GENERAL SIGNIFICANCE: Specific N-acetylhexosamine glycosylation is crucial in biological, biomedical and biotechnological applications and a good understanding of its details opens new possibilities in this fast developing area of glycoscience.
[Mh] Termos MeSH primário: Glicosídeo Hidrolases/metabolismo
Glicosiltransferases/metabolismo
Hexosaminas/metabolismo
Engenharia de Proteínas
[Mh] Termos MeSH secundário: Catálise
Glicoproteínas/biossíntese
Glicosilação
Oligossacarídeos/biossíntese
Sulfotransferases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Glycoproteins); 0 (Hexosamines); 0 (Oligosaccharides); EC 2.4.- (Glycosyltransferases); EC 2.8.2.- (Sulfotransferases); EC 3.2.1.- (Glycoside Hydrolases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE


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[PMID]:28336748
[Au] Autor:Scott JW; Oakhill JS
[Ad] Endereço:St Vincent's Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia jscott@svi.edu.au.
[Ti] Título:The sweet side of AMPK signaling: regulation of GFAT1.
[So] Source:Biochem J;474(7):1289-1292, 2017 Mar 23.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Maintaining a steady balance between nutrient supply and energy demand is essential for all living organisms and is achieved through the dynamic control of metabolic processes that produce and consume adenosine-5'-triphosphate (ATP), the universal currency of energy in all cells. A key sensor of cellular energy is the adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), which is the core component of a signaling network that regulates energy and nutrient metabolism. AMPK is activated by metabolic stresses that decrease cellular ATP, and functions to restore energy balance by orchestrating a switch in metabolism away from anabolic pathways toward energy-generating catabolic processes. A new study published in a recent issue of by Zibrova et al. shows that glutamine:fructose-6-phosphate amidotransferase-1 (GFAT1), the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), is a physiological substrate of AMPK. The HBP is an offshoot of the glycolytic pathway that drives the synthesis of uridine-5'-diphospho- -acetylglucosamine, the requisite donor metabolite needed for dynamic ß- -acetylglucosamine ( -GlcNAc) modification (O-GlcNAcylation) of cellular proteins. O-GlcNAcylation is a nutrient-sensitive post-translational modification that, like phosphorylation, regulates numerous intracellular processes. Zibrova et al. show that inhibitory phosphorylation of the GFAT1 residue Ser243 by AMPK in response to physiological or small-molecule activators leads to a reduction in cellular protein O-GlcNAcylation. Further work revealed that AMPK-dependent phosphorylation of GFAT1 promotes angiogenesis in endothelial cells. This elegant study demonstrates that the AMPK-GFAT1 signaling axis serves as an important communication point between two nutrient-sensitive signaling pathways and is likely to play a significant role in controlling physiological processes in many other tissues.
[Mh] Termos MeSH primário: Acetilglucosamina/metabolismo
Células Endoteliais/metabolismo
Metabolismo Energético/genética
Processamento de Proteína Pós-Traducional
[Mh] Termos MeSH secundário: Acilação
Linhagem Celular
Células Endoteliais/citologia
Hexosaminas/biossíntese
Seres Humanos
Neovascularização Fisiológica/genética
Fosforilação
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hexosamines); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170615
[Lr] Data última revisão:
170615
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170006


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[PMID]:28320982
[Au] Autor:Saxena B; Singh S
[Ad] Endereço:Department of Pharmacology, L. J. Institute of Pharmacy.
[Ti] Título:Comparison of three acute stress models for simulating the pathophysiology of stress-related mucosal disease.
[So] Source:Drug Discov Ther;11(2):98-103, 2017 May 30.
[Is] ISSN:1881-7831
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Stress-related mucosal disease (SRMD) is highly prevalent in intensive care patients leading to increasing treatment cost and mortality. SRMD is a disease elusive of ideal treatment. Evaluation of drugs is very pertinent for the efficient and safe treatment of SRMD. It relies mainly on in vivo screening models. There are various stress models, and till date, none of them is validated for simulating the SRMD pathophysiology. The present study aims to choose the best model, which reproduce pathophysiology of SRMD, among previously established stress models. This study evaluates ulcer index, hexosamine content, microvascular permeability, and gastric content in three acute stress models (cold-restraint, restraint, and water immersion restraint). Macroscopic pictures of the ulcerogenic stomach explain that in contrast to other models, cold-restraint stress (CRS) exposure produced marked ulcers on the fundic area of the stomach. Results of the present study depicted that each stress model significantly increased ulcer index, microvascular permeability and decreased hexosamine level, however, the maximum in the case of CRS-exposed rats. Total acidity and pH of the gastric content remains unchanged in all the stress models. On the contrary, the gastric volume significantly decreased only in case of CRS, while unchanged in other stress models. The overall results revealed that the CRS resembles the pathophysiology of SRMD closely. It is the best and feasible model among all the models to evaluate drugs for the treatment of SRMD.
[Mh] Termos MeSH primário: Temperatura Baixa
Modelos Animais de Doenças
Imersão
Ratos
Restrição Física
Úlcera Gástrica/fisiopatologia
Estresse Psicológico/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Permeabilidade Capilar/fisiologia
Mucosa Gástrica/metabolismo
Mucosa Gástrica/fisiopatologia
Hexosaminas/metabolismo
Concentração de Íons de Hidrogênio
Masculino
Ratos Wistar
Úlcera Gástrica/metabolismo
Estresse Psicológico/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hexosamines)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.5582/ddt.2016.01081



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