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Results for “Metabolic Networks and Pathways”

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At least 217 records · Page 12Linked to original sources
PubMed2007

SYSTOMONAS--an integrated database for systems biology analysis of Pseudomonas.

To provide an integrated bioinformatics platform for a systems biology approach to the biology of pseudomonads in infection and biotechnology the database SYSTOMONAS (SYSTems biology of pseudOMONAS) was established. Besides our own experimental metabolome, proteome and transcriptome data, various additional predictions of cellular processes, such as gene-regulatory networks were stored. Reconstruction of metabolic networks in SYSTOMONAS was achieved via comparative genomics. Broad data integration is realized using SOAP interfaces for the well established databases BRENDA, KEGG and PRODORIC. Several tools for the analysis of stored data and for the visualization of the corresponding results are provided, enabling a quick understanding of metabolic pathways, genomic arrangements or promoter structures of interest. The focus of SYSTOMONAS is on pseudomonads and in particular Pseudomonas aeruginosa, an opportunistic human pathogen. With this database we would like to encourage the Pseudomonas community to elucidate cellular processes of interest using an integrated systems biology strategy. The database is accessible at http://www.systomonas.de.

Bacterial Proteins↗
PubMed2007

Methods for monitoring autophagy from yeast to human.

The increasing interest in autophagy in a wide range of organisms, accompanied by an ever-growing influx of researchers into this field, necessitates a good understanding of the methodologies available to monitor this process. In this review we discuss current approaches that can be used to follow the overall process of autophagy, as well as individual steps, from yeast to human. The majority of the review considers methods that apply to macroautophagy; however, we also consider alternative types of degradation including chaperone-mediated autophagy and microautophagy. This information is meant to provide a resource for newcomers as well as a stimulus for experienced researchers who may be prompted to develop additional assays to examine autophagy-related pathways.

Animals↗
PubMed2026

Adolescent depression as a systemic multimorbidity catalyst: integrated genetic and metabolic pathway analysis.

BACKGROUND: Although adolescent depression has been linked to individual chronic conditions, its broader role in shaping multimorbidity risk remains understudied. METHODS: A total of 87,562 UK Biobank participants were included, of whom 18,851 had documented adolescent depression. Cox proportional hazards models were applied to evaluate associations between adolescent depression and 24 chronic diseases, followed by stratified analyses by sex and age. Two-sample Mendelian randomization (MR) was then conducted to infer causality for diseases showing significant associations. Genomic colocalization analyses were performed using relevant GWAS data to identify shared causal variants. Mediation analyses were performed to detect possible mediating factors, including the frailty index, KDM biological age acceleration, allostatic load and 30 circulating biomarkers. RESULTS: Adolescent depression was associated with elevated risk for 12 chronic diseases, with strongest associations for hypothyroidism (HR = 1.29 [1.18-1.42]), diabetes (HR = 1.25 [1.13-1.38]) and chronic obstructive pulmonary disease (COPD) (HR = 1.74 [1.50-2.01]). Risks were notably higher among females and younger adults. MR confirmed likely causal relationships for hypothyroidism (OR = 1.45 [1.03-2.05]), diabetes (OR = 1.01 [1.01-1.02]) and COPD (OR = 1.04 [1.02-1.06]). Genomic colocalization revealed a shared genetic signal at the CDSN/PSORS1C1 locus between adolescent depression and hypothyroidism. Mediation analyses revealed disease-specific pathways: creatinine for hypothyroidism, testosterone for diabetes, KDM biological ageing for COPD and frailty index across all three conditions. CONCLUSIONS: Adolescent depression confers systemic vulnerability through genetic and metabolic mechanisms, with amplified risks in females and individuals aged ≤55 years. These findings support early, integrated interventions to mitigate long-term multimorbidity.

Humans↗
PubMed2006

Metabolic network driven analysis of genome-wide transcription data from Aspergillus nidulans.

BACKGROUND: Aspergillus nidulans (the asexual form of Emericella nidulans) is a model organism for aspergilli, which are an important group of filamentous fungi that encompasses human and plant pathogens as well as industrial cell factories. Aspergilli have a highly diversified metabolism and, because of their medical, agricultural and biotechnological importance, it would be valuable to have an understanding of how their metabolism is regulated. We therefore conducted a genome-wide transcription analysis of A. nidulans grown on three different carbon sources (glucose, glycerol, and ethanol) with the objective of identifying global regulatory structures. Furthermore, we reconstructed the complete metabolic network of this organism, which resulted in linking 666 genes to metabolic functions, as well as assigning metabolic roles to 472 genes that were previously uncharacterized. RESULTS: Through combination of the reconstructed metabolic network and the transcription data, we identified subnetwork structures that pointed to coordinated regulation of genes that are involved in many different parts of the metabolism. Thus, for a shift from glucose to ethanol, we identified coordinated regulation of the complete pathway for oxidation of ethanol, as well as upregulation of gluconeogenesis and downregulation of glycolysis and the pentose phosphate pathway. Furthermore, on change in carbon source from glucose to ethanol, the cells shift from using the pentose phosphate pathway as the major source of NADPH (nicotinamide adenine dinucleotide phosphatase, reduced form) for biosynthesis to use of the malic enzyme. CONCLUSION: Our analysis indicates that some of the genes are regulated by common transcription factors, making it possible to establish new putative links between known transcription factors and genes through clustering.

Aspergillus nidulans↗
PubMed2006

Essential genes on metabolic maps.

Within the past five years genome-scale gene essentiality data sets have been published for ten diverse bacterial species. These data are a rich source of information about cellular networks that we are only beginning to explore. The analysis of these data, very heterogeneous in nature, is a challenging task. Even the definition of 'essential genes' in various genome-scale studies varies from genes 'absolutely required for survival' to those 'strongly contributing to fitness' and robust competitive growth. A comparative analysis of gene essentiality across multiple organisms based on projection of experimentally observed essential genes to functional roles in a collection of metabolic pathways and subsystems is emerging as a powerful tool of systems biology.

Computational Biology↗
PubMed2025

Uncovering potential biomarkers and metabolic pathways in systemic lupus erythematosus and lupus nephritis through integrated microbiome and metabolome analysis.

OBJECTIVE: This study aims to explore the relationship between gut microbiota and fecal metabolomic profiles in patients with systemic lupus erythematosus (SLE), with and without lupus nephritis (LN), in order to identify potentially relevant biomarkers and better understand their association with disease progression. METHODS: Fecal samples from 15 healthy controls (HC) and 36 SLE patients (18 SLE-nonLN and 18 SLE-LN) were analyzed using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified using Linear Discriminant Analysis Effect Size (LEfSe) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Receiver Operating Characteristic (ROC) curve analyses were used to assess the potential clinical relevance of selected metabolites. RESULTS: Beta diversity analysis demonstrated distinct microbial clustering between groups (p&#x2009;<&#x2009;0.05). SLE-LN samples showed an increased relative abundance of Proteobacteria and decreased Firmicutes compared to SLE-nonLN. Metabolomic profiling identified multiple differentially abundant metabolites, with notable enrichment in primary bile acid biosynthesis pathways (e.g., Glycocholic acid, AUC&#x2009;=&#x2009;0.951). In the SLE-nonLN group, increased Glycoursodeoxycholic acid levels (AUC&#x2009;=&#x2009;0.922) were observed in pathways related to taurine and hypotaurine metabolism. Correlation analysis indicated a negative association between Escherichia-Shigella and bile acid levels (p&#x2009;<&#x2009;0.01). CONCLUSION: This integrative analysis suggests that patients with SLE and LN harbor distinct gut microbiota and metabolomic profiles. The identified microbial taxa and metabolites may have potential as non-invasive biomarkers and could contribute to a better understanding of SLE pathogenesis and progression.

Humans↗
PubMed2026

Effects of apple phenolics on the human metabolome: modulation of key metabolic pathways.

Apples are widely recognized for their potential health benefits, partly attributed to their phenolic compounds. However, their impact on human metabolism remains incompletely understood. This study investigated metabolic effects of apple-derived phenolic compounds using untargeted metabolomics approach across multiple biofluids. In a crossover intervention study, 30 healthy men consumed a phenolic-rich apple juice or a placebo for two weeks. Blood, urine and saliva samples were collected before and after each intervention and analyzed by direct infusion ultra-high resolution mass spectrometry. Consumption of apple phenolic compounds resulted in significant alterations of the human metabolome, including increased levels of phenolic-derived degradation products and microbial-associated metabolites across all biofluids. Pathway enrichment analysis revealed pronounced effects on phenylalanine and tyrosine metabolism, as well as linoleic and arachidonic acid metabolism, Overall, these findings demonstrate that apple phenolic compounds induce measurable, microbiota-associated and systemic metabolic changes, providing new insights into their metabolic fate and biological relevance.

Humans↗
PubMed2006

An integrated model of glucose and galactose metabolism regulated by the GAL genetic switch.

Glucose and galactose are two alternative carbon sources in yeast for energy production, producing CO2 and alcohol. The yeast needs to switch from glucose to galactose metabolism as required, by transcriptional regulation of the respective metabolic enzymes. This regulation is achieved mainly through the GAL genetic switch, in addition to glucose repression mechanism. This study integrates the two metabolic pathways with the genetic regulatory circuit using the GEPASI 3.30 simulation environment, and investigates the model behavior under various nutrient conditions. Our system is successful in achieving transcriptional upregulation of the galactose metabolizing enzymes as required. Under high glucose and high galactose concentrations, the in silico yeast chooses to metabolize glucose first, after which it resorts to using the galactose available. We also show what the preferred storage macromolecules are in different metabolic pathways.

Carbohydrate Metabolism↗
PubMed2006

Metabolic pathways and biotechnological production of L-cysteine.

L-Cysteine is an important amino acid both biologically and commercially. Although most amino acids are commercially produced by fermentation, cysteine is mainly produced by protein hydrolysis. However, synthetic or biotechnological products have been preferred in the market. Biotechnological processes for cysteine production, both enzymatic and fermentative processes, are discussed. Enzymatic process, the asymmetric hydrolysis of DL-2-amino-Delta(2)-thiazoline-4-carboxylic acid to L-cysteine, has been developed and industrialized. The L-cysteine biosynthetic pathways of Escherichia coli and Corynebacterium glutamicum, which are used in many amino acid production processes, are also described. These two bacteria have basically same L-cysteine biosynthetic pathways. L-Cysteine-degrading enzymes and L-cysteine-exporting proteins both in E. coli and C. glutamicum are also described. In conclusion, for the effective fermentative production of L-cysteine directly from glucose, the combination of enhancing biosynthetic activity, weakening the degradation pathway, and exploiting the export system seems to be effective.

Corynebacterium glutamicum↗
PubMed2006

Dynamics of muscle glycogenolysis modeled with pH time course computation and pH-dependent reaction equilibria and enzyme kinetics.

Cellular metabolites are moieties defined by their specific binding constants to H+, Mg2+, and K+ or anions without ligands. As a consequence, every biochemical reaction in the cytoplasm has an associated proton stoichiometry that is generally noninteger- and pH-dependent. Therefore, with metabolic flux, pH is altered in a medium with finite buffer capacity. Apparent equilibrium constants and maximum enzyme velocities, which are functions of pH, are also altered. We augmented an earlier mathematical model of skeletal muscle glycogenolysis with pH-dependent enzyme kinetics and reaction equilibria to compute the time course of pH changes. Analysis shows that kinetics and final equilibrium states of the closed system are highly constrained by the pH-dependent parameters. This kinetic model of glycogenolysis, coupled to creatine kinase and adenylate kinase, simulated published experiments made with a cell-free enzyme mixture to reconstitute the network and to synthesize PCr and lactate in vitro. Using the enzyme kinetic and thermodynamic data in the literature, the simulations required minimal adjustments of parameters to describe the data. These results show that incorporation of appropriate physical chemistry of the reactions with accurate kinetic modeling gives a reasonable simulation of experimental data and is necessary for a physically correct representation of the metabolic network. The approach is general for modeling metabolic networks beyond the specific pathway and conditions presented here.

Animals↗
PubMed2006

Pathway analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line.

Ruminant species have evolved to metabolize the short-chain volatile fatty acids (VFA), acetate, propionate, and butyrate, to fulfill up to 70% of their nutrient energy requirements. The inherent VFA dependence of ruminant cells was exploited to add a level of increased sensitivity to the study of the role of butyrate gene-response elements in regulatory biochemical pathways. Global gene expression profiles of the bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The detailed mechanisms by which butyrate induces cell growth arrest and apoptosis were analyzed using the Ingenuity Pathways Knowledge Base. The functional category and pathway analyses of the microarray data revealed that four canonical pathways (Cell cycles: G2/M DNA damage checkpoint, and pyrimidine metabolism; G1/S checkpoint regulation and purine metabolism) were significantly perturbed. The biologically relevant networks and pathways of these genes were also identified. IGF2, TGFB1, TP53, E2F4, and CDC2 were established as being centered in these genomic networks. The present findings provide a basis for understanding the full range of the biological roles and the molecular mechanisms that butyrate may play in animal cell growth, proliferation, and energy metabolisms.

Animals↗
PubMed2006

Exposure of Lemna minor to arsenite: expression levels of the components and intermediates of the ubiquitin/proteasome pathway.

In animal cells, arsenite has been reported to cause sulfhydryl depletion, generate reactive oxygen species and increase the level of large ubiquitin-protein conjugates. Plant viability tests and DNA laddering experiments have shown that Lemna minor remains viable after exposure to 50 microM NaAsO(2) for periods of at least 6 h. However, protein metabolism is affected in two major ways: the synthesis of an array of stress proteins, which confer thermotolerance; and an increase in the amount of large ubiquitin-protein conjugates, particularly evident after 2-3 h of stress, indicative of a role for the ubiquitin/proteasome pathway. This outcome is primarily attributed to an increased availability of protein substrates during arsenite treatment for three main reasons: an increase in protein carbonyl content after 1-2 h of stress; moderate increments in the transcript levels of the sequences coding for the ubiquitin pathway components chosen as markers (polyubiquitin, E1 and E2, and the beta subunit and the ATPase subunits of the 26S proteasome); the observed increase in ubiquitin conjugates does not depend on de novo protein synthesis. This study is the first report on the involvement of the ubiquitin/proteasome pathway in response to arsenite in plants. In addition, it addresses the simultaneous expression of selected genes encoding the various components of the pathway. The results suggest that in plants, unlike in animals, the response to a relatively low level of arsenite does not induce apoptotic cell death. As a whole, the response to arsenite apparently involves a conjugation of salvage and proteolytic machineries, including heat shock protein synthesis and the ubiquitin/proteasome pathway.

Araceae↗