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1.
Braz. arch. biol. technol ; 64: e21190480, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1278442

RESUMO

Abstract The evolution of species is inevitably accompanied by the evolution of metabolic networks to adapt to different environments. The metabolic networks of different species were collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) website, and some enzyme reactions with the highest occurrence frequency in all species were found and are reported in this paper. The correlation coefficients of whether the enzyme reactions appear in all species were calculated, and the corresponding evolutionary correlation connection networks were calculated according to different correlation coefficient thresholds. These studies show that, as the evolutionary correlation of enzyme reactions increases, the weighted average of the mean functional concentration ratios of the enzyme reactions also increases, indicating that the functional concentration ratio of enzyme reactions has a certain correlation with the evolutionary correlation. The work presented in this paper enhances our understanding of the characteristics and general rules of metabolic network evolution.


Assuntos
Ativação Enzimática , Redes e Vias Metabólicas , Adaptação Biológica , Metabolismo
2.
Arch. endocrinol. metab. (Online) ; 63(6): 549-556, Nov.-Dec. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1055020

RESUMO

ABSTRACT Growth hormone (GH) is best known for its effect stimulating tissue and somatic growth through the regulation of cell division, regeneration and proliferation. However, GH-responsive neurons are spread over the entire central nervous system, suggesting that they have important roles in the brain. The objective of the present review is to summarize and discuss the potential physiological importance of GH action in the central nervous system. We provide evidence that GH signaling in the brain regulates the physiology of numerous functions such as cognition, behavior, neuroendocrine changes and metabolism. Data obtained from experimental animal models have shown that disruptions in GH signaling in specific neuronal populations can affect the reproductive axis and impair food intake during glucoprivic conditions, neuroendocrine adaptions during food restriction, and counter-regulatory responses to hypoglycemia, and they can modify gestational metabolic adaptions. Therefore, the brain is an important target tissue of GH, and changes in GH action in the central nervous system can explain some dysfunctions presented by individuals with excessive or deficient GH secretion. Furthermore, GH acts in specific neuronal populations during situations of metabolic stress to promote appropriate physiological adjustments that restore homeostasis. Arch Endocrinol Metab. 2019;63(6):549-56


Assuntos
Humanos , Encéfalo/metabolismo , Fármacos Neuroprotetores/metabolismo , Hormônio do Crescimento Humano/metabolismo , Redes e Vias Metabólicas/fisiologia , Transdução de Sinais , Regeneração Nervosa/fisiologia
3.
Braz. arch. biol. technol ; 62: e19180071, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1055371

RESUMO

Abstract 13C metabolic flux analysis (13C-MFA) has achieved increasing significance in quantitative metabolic system analysis in recent years. In 13C metabolic flux analysis, 13C-FLUX software is a major analytical tool. The software's input script is primarily expressed in textual form without visual presentation of the structure of the entire metabolic network, thus error-prone in manual input. To solve this problem, we have developed a visual FTBL generator (VFG, available at http://47.100.98.220/vfg/index.jsp in a Google or Firefox browser)for MFA that eliminates the tedious, error-prone text entry mode and provides a user-friendly graphical interface and simple visual reaction generation functions.


Assuntos
Base de Dados , Redes e Vias Metabólicas , Análise do Fluxo Metabólico , Visualização de Dados
4.
Braz. j. microbiol ; 49(2): 210-211, Apr.-June 2018.
Artigo em Inglês | LILACS | ID: biblio-889231

RESUMO

Abstract Paraburkholderia tropica (syn Burkholderia tropica) are nitrogen-fixing bacteria commonly found in sugarcane. The Paraburkholderia tropica strain Ppe8 is part of the sugarcane inoculant consortium that has a beneficial effect on yield. Here, we report a draft genome sequence of this strain elucidating the mechanisms involved in its interaction mainly with Poaceae. A genome size of approximately 8.75 Mb containing 7844 protein coding genes distributed in 526 subsystems was de novo assembled with ABySS and annotated by RAST. Genes related to the nitrogen fixation process, the secretion systems (I, II, III, IV, and VI), and related to a variety of metabolic traits, such as metabolism of carbohydrates, amino acids, vitamins, and proteins, were detected, suggesting a broad metabolic capacity and possible adaptation to plant association.


Assuntos
Genoma Bacteriano , Burkholderiaceae/genética , Endófitos/genética , Proteínas de Bactérias/genética , Análise de Sequência de DNA , Biologia Computacional , Saccharum/microbiologia , Burkholderiaceae/isolamento & purificação , Redes e Vias Metabólicas/genética , Anotação de Sequência Molecular , Endófitos/isolamento & purificação
5.
Braz. j. microbiol ; 49(2): 207-209, Apr.-June 2018. tab
Artigo em Inglês | LILACS | ID: biblio-889240

RESUMO

Abstract Streptomycetes remain as one of the important sources for bioactive products. Isolated from the mangrove forest, Streptomyces gilvigriseus MUSC 26T was previously characterised as a novel streptomycete. The high quality draft genome of MUSC 26T contained 5,213,277 bp with G + C content of 73.0%. Through genome mining, several gene clusters associated with secondary metabolites production were revealed in the genome of MUSC 26T. These findings call for further investigations into the potential exploitation of the strain for production of pharmaceutically important compounds.


Assuntos
Streptomyces/genética , Genoma Bacteriano , Microbiologia Ambiental , Streptomyces/isolamento & purificação , Composição de Bases , Produtos Biológicos/metabolismo , Análise de Sequência de DNA , Biologia Computacional , Áreas Alagadas , Redes e Vias Metabólicas/genética , Metabolismo Secundário
6.
Braz. j. microbiol ; 47(4): 835-845, Oct.-Dec. 2016. graf
Artigo em Inglês | LILACS | ID: biblio-828196

RESUMO

Abstract Rivers and streams are important reservoirs of freshwater for human consumption. These ecosystems are threatened by increasing urbanization, because raw sewage discharged into them alters their nutrient content and may affect the composition of their microbial community. In the present study, we investigate the taxonomic and functional profile of the microbial community in an urban lotic environment. Samples of running water were collected at two points in the São Pedro stream: an upstream preserved and non-urbanized area, and a polluted urbanized area with discharged sewage. The metagenomic DNA was sequenced by pyrosequencing. Differences were observed in the community composition at the two sites. The non-urbanized area was overrepresented by genera of ubiquitous microbes that act in the maintenance of environments. In contrast, the urbanized metagenome was rich in genera pathogenic to humans. The functional profile indicated that the microbes act on the metabolism of methane, nitrogen and sulfur, especially in the urbanized area. It was also found that virulence/defense (antibiotic resistance and metal resistance) and stress response-related genes were disseminated in the urbanized environment. The structure of the microbial community was altered by uncontrolled anthropic interference, highlighting the selective pressure imposed by high loads of urban sewage discharged into freshwater environments.


Assuntos
Humanos , Urbanização , Microbiologia da Água , Rios/microbiologia , Metagenoma , Microbiota , Filogenia , RNA Ribossômico 16S/genética , Ecossistema , Metabolismo Energético , Redes e Vias Metabólicas , Metagenômica , Código de Barras de DNA Taxonômico
7.
Int. j. med. surg. sci. (Print) ; 3(3): 933-941, sept. 2016.
Artigo em Espanhol | LILACS | ID: biblio-1087613

RESUMO

La vitamina D clásicamente ha sido relacionada con el metabolismo óseo, sin embargo ejerce diversas funciones en varios tejidos del organismo que poseen el receptor para vitamina D (VCR) yson susceptibles a su efecto. La disminución de vitamina D también se ha asociado a patologías "no clásicas"como hipertensión, síndrome metabólico, resistencia a insulina, diabetes, desarrollo de algunos canceres,alteraciones pulmonares, autoinmunidad e infertilidad, entre otras. También se ha asociado la deficiencia materna de vitamina D en la génesis de patologías postnatales. Además, muchas de estas patologías se producirían por alteraciones moleculares, principalmente relacionadas con su metabolismo y con polimorfismos del receptor VCR. La vitamina D se considerara una hormona, puede ser sintetizada en la piel a partir 7-dehidrocolesterol mediante radiación ultravioleta B. Su metabolismo es complejo e implica la interacción de diversos factores en su incorporación y formación final de calcitriol, su forma activa. Para ejercer su efecto requiere de la activación del receptor VDR en la célula blanco, el cual a su vez activa secuencias de genes específicos con funciones diversas, a través de secuencias promotoras del ADN denominadas elementos de respuesta de vitamina D (VDRE). Muchos tejidos presentan el receptor VDR y enzimas necesarias para su metabolismo, por lo cual el espectro de acción de la vitamina D es muy amplio, así como la variedad de patologías que produce. Esta revisión de vitamina D, está centrada principalmente en los aspectos moleculares de su metabolismo y su rol en la génesis de enfermedades "no clásicas", producto de su disminución o alteración de su metabolismo.


Vitamin D has traditionally been associated with bone metabolism, however it exerts different functions in various tissues of the body that possess the vitamin D (VCR) receptor and they are susceptible to its effect. Decreased vitamin D has also been associated with "nonclassical" diseases such as hypertension, metabolic syndrome, insulin resistance, diabetes, development of some cancers, lung disorders,autoimmunity and infertility, among others. Maternal vitamin D deficiency has been associated in the genesis of postnatal diseases. Further, many of these pathologies are produced by molecular alterations, mainly related to metabolism and receptor polymorphisms VCR. Vitamin D is considered a hormone, can be synthesized in the skin from 7-dehydrocholesterol by ultraviolet radiation B. The metabolism is complex and involves the interaction of several factors in its incorporation and final formation of calcitriol, the active form. To produce its effect requires activation of VDR receptor on the target cell, which activates specific gene sequences with different functions, through DNA promoter sequences in identified vitamin D response elements (VDRE).Many tissues have the VDR receptor and enzymes necessary for metabolism, so the spectrum of vitamin Daction is very broad in the variety of pathologies produced. This review of vitamin D focuses primarily on the molecular aspects of its metabolism and its role in the genesis of "nonclassical", diseases, product of its reduction or alteration of metabolic diseases.


Assuntos
Humanos , Vitamina D/metabolismo , Deficiência de Vitamina D/metabolismo , Receptores de Calcitriol/deficiência , Sistema Imunitário/metabolismo , Deficiência de Vitamina D/complicações , Doença/etiologia , Redes e Vias Metabólicas , Hormônios/metabolismo
8.
Braz. j. microbiol ; 47(3): 610-616, July-Sept. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-788960

RESUMO

ABSTRACT This study aimed to investigate the impact of nonionic surfactants on the efficacy of fluorine degradation by Polyporus sp. S133 in a liquid culture. Fluorene was observed to be degraded in its entirety by Polyporus sp. S133 subsequent to a 23-day incubation period. The fastest cell growth rate was observed in the initial 7 days in the culture that was supplemented with Tween 80. The degradation process was primarily modulated by the activity of two ligninolytic enzymes, laccase and MnP. The highest laccase activity was stimulated by the addition of Tween 80 (2443 U/L) followed by mixed surfactant (1766 U/L) and Brij 35 (1655 U/L). UV-vis spectroscopy, TLC analysis and mass spectrum analysis of samples subsequent to the degradation process in the culture medium confirmed the biotransformation of fluorene. Two metabolites, 9-fluorenol (λmax 270, tR 8.0 min and m/z 254) and protocatechuic acid (λmax 260, tR 11.3 min and m/z 370), were identified in the treated medium.


Assuntos
Polyporus/metabolismo , Fluorenos/metabolismo , Solubilidade , Biodegradação Ambiental , Biotransformação , Biomassa , Poluentes Ambientais/metabolismo , Redes e Vias Metabólicas , Polyporus/enzimologia , Metaboloma , Metabolômica/métodos , Fluorenos/química
9.
Braz. j. microbiol ; 46(1): 103-111, 05/2015. graf
Artigo em Inglês | LILACS | ID: lil-748233

RESUMO

Degradation of 2,4,6-trinitrotoluene (TNT), a nitroaromatic explosive found in the soil and ground water, was investigated using Pseudomonas aeruginosa in in vitro experiments. Biodegradable abilitiy of this bacteria was performed with 50 and 75 mg L−1 TNT concentrations in a defined liquid medium for 96 h time period. Treatment of TNT in supernatant samples taken at 0, 6, 12, 24, 48, 72 and 96 h from agitated vessels was followed by reverse-phase high-performance liquid chromatography (HPLC). In cultures supplemented with 50 and 75 mgL−1 TNT, after 96 h of incubation 46% and 59% reduction were detected respectively. Two metabolites as degradation intermediates with nitrite release into the medium, 2,4-dinitrotoluene (2,4-DNT) and 4-aminodinitrotoluene (4-ADNT), were elucidated by thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS). These findings clearly indicate that Pseudomonas aeruginosa can be used in bioremediation of TNT contaminated sites.


Assuntos
Redes e Vias Metabólicas , Pseudomonas aeruginosa/metabolismo , Trinitrotolueno/metabolismo , Compostos de Anilina/análise , Biotransformação , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Meios de Cultura , Dinitrobenzenos/análise , Cromatografia Gasosa-Espectrometria de Massas , Fatores de Tempo
10.
J. venom. anim. toxins incl. trop. dis ; 21: 48, 31/03/2015. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-954772

RESUMO

Background American visceral leishmaniasis is caused by the intracellular parasiteLeishmania (L.) infantum chagasi, and transmitted by the sand fly Lutzomyia longipalpis. Since treatment is based on classical chemotherapeutics with significant side effects, the search for new drugs remains the greatest global challenge. Thus, this in vitro study aimed to evaluate the leishmanicidal effect ofCrotalus durissus terrificus venom fractions on promastigote and amastigote forms of Leishmania (L.) infantum chagasi. Methods Phospholipase A 2 (PLA 2 ) and a pool of peptide fraction (<3 kDa) were purified from Crotalusvenom. Furthermore, promastigotes and peritoneal macrophages of mice infected by amastigotes were exposed to serial dilutions of the PLA 2 and peptides at intervals varying between 1.5625 μg/mL and 200 μg/mL. Both showed activity against promastigotes that varied according to the tested concentration and the time of incubation (24, 48 and 72 h). Results MTT assay for promastigotes showed IC 50 of 52.07 μg/mL for PLA2 and 16.98 μg/mL for the peptide fraction of the venom. The cytotoxicity assessment in peritoneal macrophages showed IC50 of 98 μg/mL and 16.98 μg/mL for PLA 2 and peptide by MTT assay, respectively. In peritoneal macrophages infected by Leishmania (L.) infantum chagasi amastigotes, the PLA 2 stimulated growth of parasites, and at higher doses reduced growth by 23 %. The peptide fraction prevented 43 % of the intracellular parasite growth at a dose of 16.98 μg/mL, demonstrating the toxicity of this dose to macrophages. Both fractions stimulated H 2 O 2 production by macrophages but only PLA 2 was able to stimulate NO production. Conclusion We have demonstrated the in vitro leishmanicidal activity of the PLA2 and peptide fraction ofCrotalus venom. The results encourage further studies to describe the metabolic pathways involved in cell death, as well as the prospecting of molecules with antiparasitic activity present in the peptide fraction of Crotalus durissus terrificus venom.(AU)


Assuntos
Animais , Peptídeos , Fosfolipases , Técnicas In Vitro , Crotalus cascavella/toxicidade , Leishmania , Redes e Vias Metabólicas
11.
Braz. j. microbiol ; 45(4): 1303-1308, Oct.-Dec. 2014. graf, tab
Artigo em Inglês | LILACS | ID: lil-741280

RESUMO

A previously reported o-nitrobenzaldehyde (ONBA) degrading bacterium Pseudomonas sp. ONBA-17 was further identified and characterized. Based on results of DNA base composition and DNA-DNA hybridization, the strain was identified as P. putida. Its degradation effect enhanced with increase of inoculum amount and no lag phase was observed. Higher removal rate was achieved under shaking conditions. All tested ONBA with different initial concentrations could be completely degraded within 5 d. In addition, degradative enzyme(s) involved was confirmed as intra-cellular distributed and constitutively expressed. Effects of different compounds on relative activity of degradative enzyme(s) within cell-free extract were also evaluated. Finally, 2-nitrobenzoic acid and 2, 3-dihydroxybenzoic acid were detected as metabolites of ONBA degradation by P. putida ONBA-17, and relevant metabolic pathway was preliminary proposed. This study might help with future research in better understanding of nitroaromatics biodegradation.


Assuntos
Benzaldeídos/metabolismo , Redes e Vias Metabólicas , Pseudomonas putida/metabolismo , Biotransformação , Hidroxibenzoatos/metabolismo , Nitrobenzoatos/metabolismo , Pseudomonas putida/classificação , Pseudomonas putida/genética
12.
Rio de Janeiro; s.n; 2014. 152 f p.
Tese em Português | LILACS | ID: lil-756641

RESUMO

O Trypanosoma cruzi, agente etiológico da doença de Chagas, possui um ciclo de vida complexo, deve lidar com diversas condições do ambiente e depende dos hospedeiros para suprir suas necessidades nutricionais. Uma delas é a necessidade de captar a molécula de heme (Fe-protoporfirina IX) que será utilizada como fator de crescimento. Os mecanismos envolvendo o metabolismo de heme são cruciais para a sobrevivência do T. cruzi pois o parasito não possui várias enzimas de biossíntese dessa porfirina e o heme livre pode apresentar citotoxicidade para célula. Na tentativa de perseguir o destino final do heme no parasito, nós estudamos essa via inexplorada no T. cruzi. Nessa tese, nós demonstramos que epimastigotas cultivados com heme, produziram os compostos, α-meso hidroxiheme, verdoheme e biliverdina (identificados por HPLC acoplado á espectrofotômetria). Além disso, nós observamos através de análise dos extratos de epimastigotas no espectrômetro de massas (LQT Orbitrap), espécies iônicas de m/z 583,4 e m/z 619,3. A fragmentação subsequente desses íons originaram espécies filhas típicas das moléculas de biliverdina e verdoheme, respectivamente. Nós observamos também, espécies iônicas de m/z 1397,4 e m/z 1135,4. A fragmentação dessas espécies produziram íons, sendo um deles com a mesma massa molecular de heme (m/z 616,3). Essa espécie iônica por sua vez, gerou fragmentos iônicos idênticos a uma molécula de heme, confirmando que esses intermediários são produtos da modificação da porfirina. Baseado nesses resultados, nós propomos um modelo onde o catabolismo de heme em T. cruzi, envolveria a conjugação da bis(glutationil)spermina, um derivado da tripanotiona presente em tripanossomatídeos, à porfirina (m/z 1137,4), seguido da remoção de dois resíduos de ácidos glutâmicos (m/z 1135,4)...


Trypanosoma cruzi, the causal agent of Chagas disease, has a complex life cycle and they must cope with diverse environmental conditions and depends on hosts for its nutritional needs. One of the nutritional characteristic is that they need a heme compound (Fe-protoporphyrin IX) as a growth factor. The mechanisms involved in these processes are crucial for their survival mainly because of trypanosomatids lack of the complete heme biosynthetic pathway and the cytotoxic activity of free heme. Following the fate of this porphyrin in the parasite we studied this missing pathway in T. cruzi. Here, we show that epimastigotes cultivated with heme yielded the compounds, α-meso hydroxyheme, verdoheme and biliverdin (as determined by HPLC with diode array detector). Furthermore, we observed ion species of m/z 583.4 and m/z 619.3 from epimastigotes extracts detected by direct infusion on LQT Orbitrap platform. A tipical biliverdin and verdoheme doughter-ion species were generated by m/z 583.4 and m/z 619.3 fragmentations, respectively. We also observed an ion species at m/z 1397.4 and m/z 1135. The subsequent fragmentation of this species produced a daughter-ions whose one with the same molecular mass as heme (m/z 616.4). This species, in turn, generated daughter species identical to an authentic heme, confirming that these intermediates were modified heme products. Based on these findings, we propose that heme catabolism in T. cruzi involves a additions of Bis(glutathionyl)spermine, a low molecular mass thiols occurring in trypanosomatids, to heme (m/z 1397.4), followed by removal of the glutamic residues (m/z 1135)...


Assuntos
Humanos , Biliverdina , Heme/metabolismo , Trypanosoma cruzi/fisiologia , Homeostase , Heme/fisiologia , Redes e Vias Metabólicas , Trypanosoma cruzi/crescimento & desenvolvimento
13.
Braz. j. microbiol ; 44(2): 639-647, 2013. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-688595

RESUMO

The petroleum-derived degrading Dietzia cinnamea strain P4 recently had its genome sequenced and annotated. This allowed employing the data on genes that are involved in the degradation of n-alkanes. To examine the physiological behavior of strain P4 in the presence of n-alkanes, the strain was grown under varying conditions of pH and temperature. D. cinnamea P4 was able to grow at pH 7.0-9.0 and at temperatures ranging from 35 ºC to 45 ºC. Experiments of gene expression by real-time quantitative RT-PCR throughout the complete growth cycle clearly indicated the induction of the regulatory gene alkU (TetR family) during early growth. During the logarithmic phase, a large increase in transcriptional levels of a lipid transporter gene was noted. Also, the expression of a gene that encodes the protein fused rubredoxin-alkane monooxygenase was enhanced. Both genes are probably under the influence of the AlkU regulator.


Assuntos
Actinomycetales/genética , Actinomycetales/metabolismo , Alcanos/metabolismo , Perfilação da Expressão Gênica , Genes Bacterianos , Hidrocarbonetos/metabolismo , Redes e Vias Metabólicas/genética , Actinomycetales/crescimento & desenvolvimento , Biotransformação , Concentração de Íons de Hidrogênio , Reação em Cadeia da Polimerase em Tempo Real , Temperatura
14.
Medicina (B.Aires) ; 72(3): 221-226, jun. 2012. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-657506

RESUMO

La vía TOR ("Target Of Rapamycin") de mamíferos es una red proteica de regulación para una amplia gama de procesos involucrados en el crecimiento y la diferenciación celular, constituyendo un interruptor funcional entre el metabolismo anabólico y catabólico de la célula. El Trypanosoma cruzi, agente etiológico de la enfermedad de Chagas, tiene un ciclo de vida muy complejo con diferentes estadios morfológicos en varios hospedadores. Este ciclo de vida implica que los parásitos enfrentan grandes fluctuaciones en el medio extracelular que deben ser detectadas y a las cuales deben responder adaptando su metabolismo. Un candidato a ser el mediador entre los receptores/sensores del medio y la respuesta adaptativa celular es la vía TOR. En este trabajo integramos los datos bibliográficos de la vía TOR de organismos tripanosomátidos con un análisis in silico (simulación computacional de procesos o estructuras biológicas) del genoma del parásito. Se proponen además posibles efectores y procesos regulados por esta ruta metabólica. Teniendo en cuenta que existe muy poca información sobre los mecanismos de transducción de señales en tripanosomátidos, consideramos que el mapa presentado en este trabajo puede ser una referencia para futuros trabajos experimentales.


The mammalian TOR pathway ("Target Of Rapamycin") is a regulatory protein network involved in a wide range of processes including cell growth and differentiation, providing a functional switch between anabolic and catabolic cell metabolism. Trypanosoma cruzi, the etiologic agent of Chagas disease, has a complex life cycle with different morphological stages in various hosts. This life cycle implies that parasites have to deal with fluctuations in the extracellular medium that should be detected and counteracted adapting their metabolism. A candidate to be the mediator between the receptors / sensors of the environment and cellular adaptive response is the TOR pathway. In this paper we integrate the bibliographic data of the TOR pathway in trypanosomatids by in silico analysis (computer simulation of biological structures and processes) of the parasite's genome. Possible effectors and processes regulated by this metabolic pathway are also proposed. Given that the information on the mechanisms of signal transduction in trypanosomatids is scarce, we consider the model presented in this work may be a reference for future experimental work.


Assuntos
Animais , Doença de Chagas/parasitologia , Serina-Treonina Quinases TOR/genética , Trypanosoma cruzi/genética , Simulação por Computador , Estágios do Ciclo de Vida , Redes e Vias Metabólicas , Mamíferos/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
15.
Mem. Inst. Oswaldo Cruz ; 104(8): 1100-1110, Dec. 2009. ilus, tab
Artigo em Inglês | LILACS | ID: lil-538169

RESUMO

The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopes have been placed on the use of genomic data from the human parasite Trypanosoma cruzi to identify new drug targets and develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a complete assembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functions has hampered our complete view of the parasite's metabolic pathways. Moreover, pinpointing new drug targets has proven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathways and their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an in silicocomparative study on pathway annotation and searching for analogous and specific enzymes, we have been able to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energetic pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out many enzymes that are analogous to those of the human host, which could be potential new therapeutic targets.


Assuntos
Humanos , Descoberta de Drogas , Genoma de Protozoário/genética , Redes e Vias Metabólicas/genética , Tripanossomicidas , Trypanosoma cruzi/metabolismo , Genoma de Protozoário/efeitos dos fármacos , Trypanosoma cruzi/química , Trypanosoma cruzi/genética
16.
Electron. j. biotechnol ; 12(4): 11-12, Oct. 2009. ilus, tab
Artigo em Inglês | LILACS | ID: lil-558554

RESUMO

The systematic study of the genetic fingerprint (genomics) and the biochemistry (metabolites) that goes with a specific cellular process requires the characterization of all the small molecules that form the profile of metabolites and the associated genes. The metabolome represents the collection of all the metabolites during certain process in an organism. The transcriptome represents the gene expression profile, all the messengers RNA in a defined condition. Then to understand the whole process, the studies of metabolites must be accompanied with studies of the gene expression, hence the metabolome must be accompanied by the transcriptome, so we can identify genes and metabolites whose synthesis is induced by a specific process, an infection or stress. Studies of metabolomics generate an enormous amount of data, then they need mathematical and computational tools to establish the correlations between the biochemical and genetic data, and to build up networks that represent the complex metabolic interactions that occur in each case, using tools like Graph and Networks Theory to elucidate the emergent properties inherent to the complex interactions of the metabolic maps. This paper describes the major mathematical tools that can be used for these studies, with emphasis on a semi-qualitative proposal known as the kinetic structural model.


Assuntos
Humanos , Modelos Genéticos , Metabolismo/genética , /métodos , Redes e Vias Metabólicas/genética , RNA Mensageiro/genética , RNA Mensageiro/química , Impressões Digitais de DNA/métodos , /métodos
17.
An. Fac. Med. (Perú) ; 69(3): 168-171, jul.-sept. 2008. graf
Artigo em Espanhol | LILACS, LIPECS | ID: lil-564596

RESUMO

Objetivo: Predecir, usando métodos bioinformáticos, las vías metabólicas preferentemente activas en Mycobacterium tuberculosis (MT), bajo condiciones de hipoxia. Diseño: Análisis biológico. Lugar: Instituto de Química Biológica, Microbiología y Biotecnología Marco Antonio Garrido Malo, Facultad de Farmacia y Bioquímica, UNMSM. Material biológico: Genes de Mycobacterium tuberculosis. Métodos: Inicialmente se seleccionó 355 genes de MT H37Rv, cuya expresión ha sido demostrada que es inducida bajo condiciones de hipoxia, y 359 cuya expresión es reprimida. Usando la información de secuencia de los genes con expresión inducida y reprimida, se analizó de modo comparativo la posición en el genoma de cada grupo de genes, así como algunas propiedades fisicoquímicas (punto isoeléctrico y momento hidrofóbico) de sus proteínas correspondientes. Posteriormente, a cada gen se le asignó una vía metabólica o regulatoria, usando la información sobre MT de la librería de genes y genomas de Kyoto (KEGG), y el procesamiento de secuencias, empleando el programa PATH-A. Principales medidas de resultados: Vías metabólicas en genes de Mycobacterium tuberculosis, bajo condiciones de hipoxia. Resultados: No se encontró diferencias entre los genes con expresión inducida y reprimida, en su distribución en el genoma de MT, así como en la distribución de los valores para las propiedades fisicoquímicas analizadas en sus productos. De los 355 genes con expresión inducida iniciales, solamente fue posible asignar al menos una vía metabólica a 95, usando KEGG, y 57, usando PATH-A. Conclusiones: El análisis comparativo de las vías metabólicas asignadas a los genes con expresión inducida y reprimida reveló que, bajo condiciones de hipoxia, se encuentran reprimidos muchos genes relacionados a vías metabólicas que implican gasto de ATP, encontrándose inducidos algunos genes cuyas proteínas participan en vías del metabolismo central.


Objective: To predict by using bioinformatic tools Mycobacterium tuberculosis (MT) metabolic pathways under hypoxic conditions. Design: Biology analysis. Setting: Instituto de Química Biológica, Microbiología y Biotecnología Marco Antonio Garrido Malo Biological, Microbiologic and Biotechnologic Chemistry Institute, Faculty of Pharmacy and Biochemistry, UNMSM. Biologic material: Mycobacterium tuberculosis genes. Methods: The study began with the selection of 355 genes of MT H37Rv whose expression has been shown by other studies is induced by hypoxic conditions and 359 genes whose expression was repressed. Up and down expressed genes were comparatively analyzed, localizing genes of each group within the MT genome and predicting some physicochemical properties (isoelectric point and hydrophobic moment) for their protein products. In order to assign a metabolic or regulatory pathway to each gene, Kyoto Encyclopedia of Genes and Genomes (KEGG) and PATH-A sequence analysis tool were used. Main outcome measures: Metabolic pathways in Mycobacterium tuberculosis genes under hypoxia conditions. Results: From the initial 355 up expressed genes, it was possible to assign metabolic pathways to only 95 using KEGG and 57 using PATH-A. Conclusions: There were no differences between up and down expressed genes for their genome distribution and values for studied physicochemical properties of their protein products. The comparative analysis of the assigned metabolic pathways to down and up-expressed genes revealed that under hypoxic conditions several metabolic pathways related to ATP spent were down-expressed, being induced some genes whose proteins participate incentral metabolism pathways such as the pyruvate metabolism, glycolysis and citric acid cycle.


Assuntos
Humanos , Hipóxia , Mycobacterium tuberculosis , Redes e Vias Metabólicas
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