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[PMID]:29311556
[Au] Autor:Springsteen G; Yerabolu JR; Nelson J; Rhea CJ; Krishnamurthy R
[Ad] Endereço:Department of Chemistry, Furman University, Greenville, SC, 29613, USA.
[Ti] Título:Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle.
[So] Source:Nat Commun;9(1):91, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The development of metabolic approaches towards understanding the origins of life, which have focused mainly on the citric acid (TCA) cycle, have languished-primarily due to a lack of experimentally demonstrable and sustainable cycle(s) of reactions. We show here the existence of a protometabolic analog of the TCA involving two linked cycles, which convert glyoxylate into CO and produce aspartic acid in the presence of ammonia. The reactions proceed from either pyruvate, oxaloacetate or malonate in the presence of glyoxylate as the carbon source and hydrogen peroxide as the oxidant under neutral aqueous conditions and at mild temperatures. The reaction pathway demonstrates turnover under controlled conditions. These results indicate that simpler versions of metabolic cycles could have emerged under potential prebiotic conditions, laying the foundation for the appearance of more sophisticated metabolic pathways once control by (polymeric) catalysts became available.
[Mh] Termos MeSH primário: Dióxido de Carbono/química
Glioxilatos/química
Modelos Químicos
Origem da Vida
Ácido Oxaloacético/química
Ácido Pirúvico/química
[Mh] Termos MeSH secundário: Amônia/química
Ácido Aspártico/química
Descarboxilação
Peróxido de Hidrogênio/química
Concentração de Íons de Hidrogênio
Cinética
Malonatos/química
Redes e Vias Metabólicas
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Glyoxylates); 0 (Malonates); 142M471B3J (Carbon Dioxide); 2F399MM81J (Oxaloacetic Acid); 30KYC7MIAI (Aspartic Acid); 7664-41-7 (Ammonia); 8558G7RUTR (Pyruvic Acid); 9KX7ZMG0MK (malonic acid); BBX060AN9V (Hydrogen Peroxide); JQ39C92HH6 (glyoxylic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02591-0


  2 / 1640 MEDLINE  
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[PMID]:28634235
[Au] Autor:Khaliullin B; Ayikpoe R; Tuttle M; Latham JA
[Ad] Endereço:From the Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado 80208.
[Ti] Título:Mechanistic elucidation of the mycofactocin-biosynthetic radical -adenosylmethionine protein, MftC.
[So] Source:J Biol Chem;292(31):13022-13033, 2017 Aug 04.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ribosomally synthesized and posttranslationally modified peptide (RiPP) pathways produce a diverse array of natural products. A subset of these pathways depends on radical -adenosylmethionine proteins to modify the RiPP-produced peptide. Mycofactocin biosynthesis is one example of an -adenosylmethionine protein-dependent RiPP pathway. Recently, it has been shown that MftC catalyzes the oxidative decarboxylation of the C-terminal tyrosine (Tyr-30) on the mycofactocin precursor peptide MftA; however, this product has not been verified by techniques other than MS. Herein, we provide a more detailed study of MftC catalysis and report a revised mechanism for MftC chemistry. We show that MftC catalyzes the formation of two isomeric products. Using a combination of MS, isotope labeling, and H and C NMR techniques, we established that the major product, MftA*, is a tyramine-valine-cross-linked peptide formed by MftC through two -adenosylmethionine-dependent turnovers. In addition, we show that the hydroxyl group on MftA Tyr-30 is required for MftC catalysis. Furthermore, we show that a substitution in the penultimate MftA Val-29 position causes the accumulation of an MftA** minor product. The H NMR spectrum indicates that this minor product contains an αß-unsaturated bond that likely arises from an aborted intermediate of MftA* synthesis. The finding that MftA* is the major product formed during MftC catalysis could have implications for the further elucidation of mycofactocin biosynthesis.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Carboxiliases/metabolismo
Chaperonas Moleculares/metabolismo
Mycobacterium ulcerans/enzimologia
Precursores de Proteínas/metabolismo
S-Adenosilmetionina/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Biocatálise
Carboxiliases/química
Carboxiliases/genética
Cromatografia Líquida de Alta Pressão
Descarboxilação
Chaperonas Moleculares/química
Chaperonas Moleculares/genética
Mutagênese Sítio-Dirigida
Mutação
Mycobacterium ulcerans/metabolismo
Ressonância Magnética Nuclear Biomolecular
Oxirredução
Domínios e Motivos de Interação entre Proteínas
Precursores de Proteínas/química
Precursores de Proteínas/genética
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Espectrometria de Massas por Ionização por Electrospray
Estereoisomerismo
Espectrometria de Massas em Tandem
Tiramina/química
Tiramina/metabolismo
Tirosina/química
Tirosina/metabolismo
Valina/química
Valina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Molecular Chaperones); 0 (Protein Precursors); 0 (Recombinant Fusion Proteins); 42HK56048U (Tyrosine); 7LP2MPO46S (S-Adenosylmethionine); EC 4.1.1.- (Carboxy-Lyases); HG18B9YRS7 (Valine); X8ZC7V0OX3 (Tyramine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.795682


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[PMID]:28603981
[Au] Autor:Hsieh CH; Huang X; Amaya JA; Rutland CD; Keys CL; Groves JT; Austin RN; Makris TM
[Ad] Endereço:Department of Chemistry and Biochemistry, University of South Carolina , Columbia, South Carolina 29208, United States.
[Ti] Título:The Enigmatic P450 Decarboxylase OleT Is Capable of, but Evolved To Frustrate, Oxygen Rebound Chemistry.
[So] Source:Biochemistry;56(26):3347-3357, 2017 Jul 05.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OleT is a cytochrome P450 enzyme that catalyzes the removal of carbon dioxide from variable chain length fatty acids to form 1-alkenes. In this work, we examine the binding and metabolic profile of OleT with shorter chain length (n ≤ 12) fatty acids that can form liquid transportation fuels. Transient kinetics and product analyses confirm that OleT capably activates hydrogen peroxide with shorter substrates to form the high-valent intermediate Compound I and largely performs C-C bond scission. However, the enzyme also produces fatty alcohol side products using the high-valent iron oxo chemistry commonly associated with insertion of oxygen into hydrocarbons. When presented with a short chain fatty acid that can initiate the formation of Compound I, OleT oxidizes the diagnostic probe molecules norcarane and methylcyclopropane in a manner that is reminiscent of reactions of many CYP hydroxylases with radical clock substrates. These data are consistent with a decarboxylation mechanism in which Compound I abstracts a substrate hydrogen atom in the initial step. Positioning of the incipient substrate radical is a crucial element in controlling the efficiency of activated OH rebound.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Caproatos/metabolismo
Caprilatos/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
Ácidos Decanoicos/metabolismo
Ácidos Láuricos/metabolismo
Micrococcus/enzimologia
Modelos Moleculares
[Mh] Termos MeSH secundário: Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Biocatálise
Biocombustíveis/análise
Caprilatos/química
Carboxiliases/química
Carboxiliases/genética
Carboxiliases/metabolismo
Domínio Catalítico
Ciclopropanos/química
Ciclopropanos/metabolismo
Sistema Enzimático do Citocromo P-450/química
Sistema Enzimático do Citocromo P-450/genética
Ácidos Decanoicos/química
Descarboxilação
Guaiacol/metabolismo
Peróxido de Hidrogênio/química
Peróxido de Hidrogênio/metabolismo
Ácidos Láuricos/química
Conformação Molecular
Oxirredução
Especificidade por Substrato
Terpenos/química
Terpenos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Biofuels); 0 (Caproates); 0 (Caprylates); 0 (Cyclopropanes); 0 (Decanoic Acids); 0 (Lauric Acids); 0 (Terpenes); 1F8SN134MX (hexanoic acid); 4G9EDB6V73 (decanoic acid); 594-11-6 (1-methylcyclopropane); 6JKA7MAH9C (Guaiacol); 9035-51-2 (Cytochrome P-450 Enzyme System); BBX060AN9V (Hydrogen Peroxide); EC 4.1.1.- (Carboxy-Lyases); OBL58JN025 (octanoic acid); ZGC3T0R48Q (norcarane)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171029
[Lr] Data última revisão:
171029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00338


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[PMID]:28274419
[Au] Autor:Yuan Y; Tarres A; Bessaire T; Stadler RH; Delatour T
[Ad] Endereço:College of Food Science and Engineering, Jilin University, 130062 Changchun, China; Nestlé Research Centre, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland. Electronic address: yuan_yuan@jlu.edu.cn.
[Ti] Título:Heat-induced formation of mepiquat by decarboxylation of pipecolic acid and its betaine derivative. Part 1: Model system studies.
[So] Source:Food Chem;227:173-178, 2017 Jul 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This study describes, for the first time, the role of pipecolic acid betaine and pipecolic acid, naturally present in some foods, in the formation of the plant growth regulator N,N-dimethylpiperidinium (mepiquat) under dry thermal conditions. The formation of mepiquat and intermediate compounds was investigated in model systems using high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. Mepiquat is released with a yield of up to 0.66mol% after thermal treatment (>150°C) of pipecolic acid betaine. Similar conversion rates are attained with the congener piperidine-2-carboxylic acid (dl-pipecolic acid), albeit in the presence of alkylating agents, such as choline, glycine betaine or trigonelline, that are fairly widespread in food crops. These new pathways to mepiquat indicate that the occurrence of low levels of this thermally induced compound is probably more widespread in processed foods than initially suspected (see Part 2 of this study on the occurrence of mepiquat in selected foodstuffs).
[Mh] Termos MeSH primário: Manipulação de Alimentos
Ácidos Pipecólicos/química
Piperidinas/análise
[Mh] Termos MeSH secundário: Betaína/química
Cromatografia Líquida
Descarboxilação
Temperatura Alta
Espectrometria de Massas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pipecolic Acids); 0 (Piperidines); 3SCV180C9W (Betaine); S2SFZ0Z4TW (mepiquat)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170519
[Lr] Data última revisão:
170519
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE


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[PMID]:28273096
[Au] Autor:Pankow JF; Kim K; McWhirter KJ; Luo W; Escobedo JO; Strongin RM; Duell AK; Peyton DH
[Ad] Endereço:Department of Chemistry, Portland State University, Portland, Oregon, United States of America.
[Ti] Título:Benzene formation in electronic cigarettes.
[So] Source:PLoS One;12(3):e0173055, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/OBJECTIVE: The heating of the fluids used in electronic cigarettes ("e-cigarettes") used to create "vaping" aerosols is capable of causing a wide range of degradation reaction products. We investigated formation of benzene (an important human carcinogen) from e-cigarette fluids containing propylene glycol (PG), glycerol (GL), benzoic acid, the flavor chemical benzaldehyde, and nicotine. METHODS/MAIN RESULTS: Three e-cigarette devices were used: the JUULTM "pod" system (provides no user accessible settings other than flavor cartridge choice), and two refill tank systems that allowed a range of user accessible power settings. Benzene in the e-cigarette aerosols was determined by gas chromatography/mass spectrometry. Benzene formation was ND (not detected) in the JUUL system. In the two tank systems benzene was found to form from propylene glycol (PG) and glycerol (GL), and from the additives benzoic acid and benzaldehyde, especially at high power settings. With 50:50 PG+GL, for tank device 1 at 6W and 13W, the formed benzene concentrations were 1.9 and 750 µg/m3. For tank device 2, at 6W and 25W, the formed concentrations were ND and 1.8 µg/m3. With benzoic acid and benzaldehyde at ~10 mg/mL, for tank device 1, values at 13W were as high as 5000 µg/m3. For tank device 2 at 25W, all values were ≤~100 µg/m3. These values may be compared with what can be expected in a conventional (tobacco) cigarette, namely 200,000 µg/m3. Thus, the risks from benzene will be lower from e-cigarettes than from conventional cigarettes. However, ambient benzene air concentrations in the U.S. have typically been 1 µg/m3, so that benzene has been named the largest single known cancer-risk air toxic in the U.S. For non-smokers, chronically repeated exposure to benzene from e-cigarettes at levels such as 100 or higher µg/m3 will not be of negligible risk.
[Mh] Termos MeSH primário: Benzeno/química
Sistemas Eletrônicos de Liberação de Nicotina
[Mh] Termos MeSH secundário: Ciclização
Descarboxilação
Desidratação
Cromatografia Gasosa-Espectrometria de Massas
Seres Humanos
Espectroscopia de Ressonância Magnética
Nicotina/análise
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
6M3C89ZY6R (Nicotine); J64922108F (Benzene)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173055


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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]:28144940
[Au] Autor:Matthews S; Tee KL; Rattray NJ; McLean KJ; Leys D; Parker DA; Blankley RT; Munro AW
[Ad] Endereço:Manchester Institute of Biotechnology, Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), School of Chemistry, The University of Manchester, UK.
[Ti] Título:Production of alkenes and novel secondary products by P450 OleT using novel H O -generating fusion protein systems.
[So] Source:FEBS Lett;591(5):737-750, 2017 Mar.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Jeotgalicoccus sp. 8456 OleT (CYP152L1) is a fatty acid decarboxylase cytochrome P450 that uses hydrogen peroxide (H O ) to catalyse production of terminal alkenes, which are industrially important chemicals with biofuel applications. We report enzyme fusion systems in which Streptomyces coelicolor alditol oxidase (AldO) is linked to OleT . AldO oxidizes polyols (including glycerol), generating H O as a coproduct and facilitating its use for efficient OleT -dependent fatty acid decarboxylation. AldO activity is regulatable by polyol substrate titration, enabling control over H O supply to minimize oxidative inactivation of OleT and prolong activity for increased alkene production. We also use these fusion systems to generate novel products from secondary turnover of 2-OH and 3-OH myristic acid primary products, expanding the catalytic repertoire of OleT .
[Mh] Termos MeSH primário: Oxirredutases do Álcool/metabolismo
Alcenos/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
Ácidos Graxos/metabolismo
Peróxido de Hidrogênio/metabolismo
Microbiologia Industrial
Proteínas Recombinantes de Fusão/metabolismo
[Mh] Termos MeSH secundário: Oxirredutases do Álcool/genética
Biocatálise
Biocombustíveis
Sistema Enzimático do Citocromo P-450/genética
Descarboxilação
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Engenharia Metabólica
Ácido Mirístico/metabolismo
Oxirredução
Proteínas Recombinantes de Fusão/genética
Staphylococcaceae/enzimologia
Staphylococcaceae/genética
Streptomyces coelicolor/enzimologia
Streptomyces coelicolor/genética
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Alkenes); 0 (Biofuels); 0 (Fatty Acids); 0 (Recombinant Fusion Proteins); 0I3V7S25AW (Myristic Acid); 9035-51-2 (Cytochrome P-450 Enzyme System); BBX060AN9V (Hydrogen Peroxide); EC 1.1.- (Alcohol Oxidoreductases); EC 1.1.99.- (alditol oxidase (FAD), Streptomyces coelicolor)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170202
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12581


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[PMID]:28142188
[Au] Autor:Farine L; Jelk J; Choi JY; Voelker DR; Nunes J; Smith TK; Bütikofer P
[Ad] Endereço:Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, 3012, Switzerland.
[Ti] Título:Phosphatidylserine synthase 2 and phosphatidylserine decarboxylase are essential for aminophospholipid synthesis in Trypanosoma brucei.
[So] Source:Mol Microbiol;104(3):412-427, 2017 May.
[Is] ISSN:1365-2958
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phosphatidylethanolamine (PE) and phosphatidylserine (PS) are ubiquitously expressed and metabolically interconnected glycerophospholipids in eukaryotes and prokaryotes. In Trypanosoma brucei, PE synthesis has been shown to occur mainly via the Kennedy pathway, one of the three routes leading to PE synthesis in eukaryotes, while PS synthesis has not been studied experimentally. We now reveal the importance of T. brucei PS synthase 2 (TbPSS2) and T. brucei PS decarboxylase (TbPSD), two key enzymes involved in aminophospholipid synthesis, for trypanosome viability. By using tetracycline-inducible down-regulation of gene expression and in vivo and in vitro metabolic labeling, we found that TbPSS2 (i) is necessary for normal growth of procyclic trypanosomes, (ii) localizes to the endoplasmic reticulum and (iii) represents the unique route for PS formation in T. brucei. In addition, we identified TbPSD as type I PS decarboxylase in the mitochondrion and found that it is processed proteolytically at a WGSS cleavage site into a heterodimer. Down-regulation of TbPSD expression affected mitochondrial integrity in both procyclic and bloodstream form trypanosomes, decreased ATP production via oxidative phosphorylation in procyclic form and affected parasite growth.
[Mh] Termos MeSH primário: Carboxiliases/metabolismo
Transferases de Grupos Nitrogenados/metabolismo
Trypanosoma brucei brucei/enzimologia
[Mh] Termos MeSH secundário: Descarboxilação
Mitocôndrias/metabolismo
Fosforilação Oxidativa
Fosfatidiletanolaminas/metabolismo
Fosfatidilserinas/metabolismo
Proteínas de Protozoários/metabolismo
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphatidylethanolamines); 0 (Phosphatidylserines); 0 (Protozoan Proteins); 39382-08-6 (phosphatidylethanolamine); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.99.- (Ptdss2 protein, mouse); EC 4.1.1.- (Carboxy-Lyases); EC 4.1.1.65 (phosphatidylserine decarboxylase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170530
[Lr] Data última revisão:
170530
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE
[do] DOI:10.1111/mmi.13637


  9 / 1640 MEDLINE  
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[PMID]:28092273
[Au] Autor:Kischkel S; Bergt S; Brock B; von Grönheim J; Herbst A; Epping MJ; Matheis G; Novosel E; Schneider J; Warnke P; Podbielski A; Roesner JP; Lelkes PI; Vollmar B
[Ad] Endereço:From the *Institute for Experimental Surgery, Rostock University Medical Center, Rostock, Germany; †Department of General, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center, Rostock, Germany; ‡Clinic for Anesthesiology and Intensive Care Medicine, Rostock University Medical Center, Rostock, Germany; §Novalung GmbH, Heilbronn, Germany; ¶Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center, Rostock, Germany; ‖Clinic for Anesthesiology and Intensive Care Medicine, Südstadtklinikum Rostock, Germany; and #Department of Bioengineering, Temple University, Philadelphia, Pennsylvania.
[Ti] Título:In Vivo Testing of Extracorporeal Membrane Ventilators: iLA-Activve Versus Prototype I-Lung.
[So] Source:ASAIO J;63(2):185-192, 2017 Mar/Apr.
[Is] ISSN:1538-943X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A side-by-side comparison of the decarboxylation efficacy of two pump-driven venovenous extracorporeal lung assist devices, i.e., a first prototype of the new miniaturized ambulatory extracorporeal membrane ventilator, I-lung versus the commercial system iLA-activve for more than a period of 72 hours in a large animal model. Fifteen German Landrace pigs were anesthetized and underwent mechanical hypoventilation to induce severe hypercapnia. Decarboxylation was accomplished by either the I-lung or the iLA-activve via a double lumen catheter in the jugular vein. Sham-operated pigs were not connected to extracorporeal devices. Cardiovascular, respiratory, and metabolic parameters were continuously monitored, combined with periodic arterial blood sampling for subsequent clinical blood diagnostics, such as gas exchange, hemolysis, coagulation parameters, and cytokine profiles. At the termination of the studies, lung tissue was harvested and examined histologically for pulmonary morphology and leukocyte tissue infiltration. Both extracorporeal devices showed high and comparable efficacy with respect to carbon dioxide elimination for more than 72 hours and were not associated with either bleeding events or clotting disorders. Pigs of both groups showed cardiovascular and hemodynamic stability without marked differences to sham-operated animals. Groups also did not differ in terms of inflammatory and metabolic parameters. We established a preclinical in vivo porcine model for comparative long-term testing of I-lung and iLA-activve. The I-lung prototype proved to be safe and feasible, providing adequate decarboxylation without any adverse events. Once translated into the clinical treatment, the new miniaturized and transportable I-lung device might represent a promising tool for treating awake and mobilized patients with decompensated pulmonary disorders.
[Mh] Termos MeSH primário: Oxigenação por Membrana Extracorpórea
Pneumopatias/terapia
Ventiladores Mecânicos
[Mh] Termos MeSH secundário: Animais
Dióxido de Carbono/sangue
Descarboxilação
Modelos Animais
Oxigênio/sangue
Suínos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
142M471B3J (Carbon Dioxide); S88TT14065 (Oxygen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE
[do] DOI:10.1097/MAT.0000000000000465


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[PMID]:27693268
[Au] Autor:Kingston NL; Liu Y; Calderone CT
[Ad] Endereço:Department of Chemistry, Carleton College, 1 North College Street, Northfield, MN 55057, USA.
[Ti] Título:ORF7 from Amycolatopsis orientalis catalyzes decarboxylation of N -methylarginine and amine oxidation of arginine: Biosynthetic implications.
[So] Source:Biochim Biophys Acta;1865(1):99-106, 2017 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A key step in the biosynthesis of the polyene polyketide ECO-0501 by Amycolatopsis orientalis ATCC 43491 is thought to involve oxidative decarboxylation of arginine or N -methylarginine to the corresponding primary amide. This reaction is the centerpiece of a recently identified biosynthetic cassette that generates 4-guanidinobutyryl thioesters to serve as starter units for polyketide synthesis. We examined the reaction of ORF7, the predicted ECO-0501 biosynthetic decarboxylase, with arginine, and saw no evidence of decarboxylation. Instead, we observed exclusive amine oxidation to generate 2-oxoarginine, with a k /K of 5.6×10 M s , typical of values measured for physiological amino acid decarboxylases. In contrast, when ORF7 was incubated with N -methylarginine, we observed exclusive decarboxylation to generate 4-(N -methylguanidino)butyramide. These differing reactive pathways provide insight into the biosyntheses of guanidinobutyryl-derived polyketides and demonstrate the biosynthetic versatility of arginine-processing decarboxylases. In addition, it suggests that ORF7 may be an incisive model system for dissecting the determinants of flavoprotein-catalyzed oxidase and monooxygenase modes of reactivity.
[Mh] Termos MeSH primário: Actinobacteria/enzimologia
Proteínas de Bactérias/metabolismo
Carboxiliases/metabolismo
Ácidos Graxos Insaturados/biossíntese
[Mh] Termos MeSH secundário: Amidas/metabolismo
Arginina/metabolismo
Biocatálise
Descarboxilação
Guanidinas
Modelos Moleculares
Oxirredução
ômega-N-Metilarginina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (13-hydroxy-2,12,14,16,22-pentamethyl-28-(N-methyl-guanidino)-octacosa-2,4,6,8,10,14,20,24-octaenoic acid (2-hydroxy-5-oxo-cyclopent-1-enyl)-amide); 0 (Amides); 0 (Bacterial Proteins); 0 (Fatty Acids, Unsaturated); 0 (Guanidines); 27JT06E6GR (omega-N-Methylarginine); 94ZLA3W45F (Arginine); EC 4.1.1.- (Carboxy-Lyases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE



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