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Fluxomics
Fluxomics describes the various approaches that seek to determine the rates of metabolic reactions within a biological entity. While metabolomics can provide instantaneous information on the metabolites in a biological sample, metabolism is a dynamic process. The significance of fluxomics is that metabolic fluxes determine the cellular phenotype. It has the added advantage of being based on the metabolome which has fewer components than the genome or proteome. Fluxomics falls within the field of systems biology which developed with the appearance of high throughput technologies. Systems biology recognizes the complexity of biological systems and has the broader goal of explaining and predicting this complex behavior. Metabolic flux Metabolic flux refers to the rate of metabolite conversion in a metabolic network. For a reaction this rate is a function of both enzyme abundance and enzyme activity. Enzyme concentration is itself a function of transcriptional and translational ...
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Metabolic Flux Analysis
Metabolic flux analysis (MFA) is an experimental fluxomics technique used to examine production and consumption rates of metabolites in a biological system. At an intracellular level, it allows for the quantification of metabolic Flux (metabolism), fluxes, thereby elucidating the central metabolism of the cell. Various methods of MFA, including isotopically stationary metabolic flux analysis, isotopically non-stationary metabolic flux analysis, and thermodynamics-based metabolic flux analysis, can be coupled with Metabolic network modelling, stoichiometric models of metabolism and mass spectrometry methods with isotopic mass resolution to elucidate the transfer of Moiety (chemistry), moieties containing isotopic tracers from one metabolite into another and derive information about the metabolic network. Metabolic flux analysis (MFA) has many applications such as determining the limits on the ability of a biological system to produce a biochemical such as ethanol, predicting the respo ...
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Metabolic Network Modelling
Metabolic network modelling, also known as metabolic network reconstruction or metabolic pathway analysis, allows for an in-depth insight into the molecular mechanisms of a particular organism. In particular, these models correlate the genome with molecular physiology. A reconstruction breaks down metabolic pathways (such as glycolysis and the citric acid cycle) into their respective reactions and enzymes, and analyzes them within the perspective of the entire network. In simplified terms, a reconstruction collects all of the relevant metabolic information of an organism and compiles it in a mathematical model. Validation and analysis of reconstructions can allow identification of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. This knowledge can then be applied to create novel biotechnology. In general, the process to build a reconstruction is as follows: # Draft a reconstruction # Refine the model # Convert mod ...
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Metabolic
Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks of proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word ''metabolism'' can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary (or intermediate) metabolism. Metabolic reactions may be categorized as '' catabolic''—the ''breaking down'' of compounds (for example, of glucose to pyruvate by cellular respira ...
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Metabolome
The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The small molecule chemicals found in a given metabolome may include both endogenous metabolites that are naturally produced by an organism (such as amino acids, organic acids, nucleic acids, fatty acids, amines, sugars, vitamins, co-factors, pigments, antibiotics, etc.) as well as exogenous chemicals (such as drugs, environmental contaminants, food additives, toxins and other xenobiotics) that are not naturally produced by an organism. In other words, there is both an endogenous metabolome and an exogenous metabolome. The endogenous metabolome can be further subdivided to include a "primary" and a "secondary" metabolome (particularly when referring to plant or microbial metabolomes). A primary metabolite is directly involved in the nor ...
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Systems Biology
Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological systems, using a holistic approach (holism instead of the more traditional reductionist, reductionism) to biological research. This multifaceted research domain necessitates the collaborative efforts of chemists, biologists, mathematicians, physicists, and engineers to decipher the biology of intricate living systems by merging various quantitative molecular measurements with carefully constructed mathematical models. It represents a comprehensive method for comprehending the complex relationships within biological systems. In contrast to conventional biological studies that typically center on isolated elements, systems biology seeks to combine different biological data to create models that illustrate and elucidate the dynamic interactions with ...
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Flux Balance Analysis
In biochemistry, flux balance analysis (FBA) is a mathematical method for simulating the metabolism of cells or entire unicellular organisms, such as ''Escherichia coli, E. coli'' or yeast, using genome-scale reconstructions of metabolic networks. Genome-scale reconstructions describe all the biochemical reactions in an organism based on its entire genome. These reconstructions model metabolism by focusing on the interactions between metabolites, identifying which metabolites are involved in the various reactions taking place in a cell or organism, and determining the genes that encode the enzymes which Enzyme catalysis, catalyze these reactions (if any). History Earliest work in FBA dates back to the early 1980s. Papoutsakis demonstrated that it was possible to construct flux balance equations using a metabolic map. It was Watson,Watson MR (1984) Metabolic maps for the Apple II. 12, 1093-1094 however, who first introduced the idea of using linear programming and an objective f ...
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Stoichiometric
Stoichiometry () is the relationships between the masses of reactants and products before, during, and following chemical reactions. Stoichiometry is based on the law of conservation of mass; the total mass of reactants must equal the total mass of products, so the relationship between reactants and products must form a ratio of positive integers. This means that if the amounts of the separate reactants are known, then the amount of the product can be calculated. Conversely, if one reactant has a known quantity and the quantity of the products can be empirically determined, then the amount of the other reactants can also be calculated. This is illustrated in the image here, where the unbalanced equation is: : : However, the current equation is imbalanced. The reactants have 4 hydrogen and 2 oxygen atoms, while the product has 2 hydrogen and 3 oxygen. To balance the hydrogen, a coefficient of 2 is added to the product H2O, and to fix the imbalance of oxygen, it is also added ...
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Chemical Kinetics
Chemical kinetics, also known as reaction kinetics, is the branch of physical chemistry that is concerned with understanding the rates of chemical reactions. It is different from chemical thermodynamics, which deals with the direction in which a reaction occurs but in itself tells nothing about its rate. Chemical kinetics includes investigations of how experimental conditions influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition states, as well as the construction of mathematical models that also can describe the characteristics of a chemical reaction. History The pioneering work of chemical kinetics was done by German chemist Ludwig Wilhelmy in 1850. He experimentally studied the rate of inversion of sucrose and he used integrated rate law for the determination of the reaction kinetics of this reaction. His work was noticed 34 years later by Wilhelm Ostwald. In 1864, Peter Waage and Cato Guldberg published the law ...
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Metabolic Network
A metabolic network is the complete set of metabolic and physical processes that determine the physiological and biochemical properties of a cell. As such, these networks comprise the chemical reactions of metabolism, the metabolic pathways, as well as the regulatory interactions that guide these reactions. With the sequencing of complete genomes, it is now possible to reconstruct the network of biochemical reactions in many organisms, from bacteria to human. Several of these networks are available online: Kyoto Encyclopedia of Genes and Genomes ( KEGG), EcoCyc, BioCyc and metaTIGER. Metabolic networks are powerful tools for studying and modelling metabolism. Uses Metabolic networks can be used to detect comorbidity patterns in diseased patients. Certain diseases, such as obesity and diabetes, can be present in the same individual concurrently, sometimes one disease being a significant risk factor for the other disease. The disease phenotypes themselves are normally the c ...
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Isotopic Labeling
Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through chemical reaction, metabolic pathway, or a biological cell. The reactant is 'labeled' by replacing one or more specific atoms with their isotopes. The reactant is then allowed to undergo the reaction. The position of the isotopes in the products is measured to determine what sequence the isotopic atom followed in the reaction or the cell's metabolic pathway. The nuclides used in isotopic labeling may be stable nuclides or radionuclides. In the latter case, the labeling is called radiolabeling. In isotopic labeling, there are multiple ways to detect the presence of labeling isotopes; through their mass, vibrational mode, or radioactive decay. Mass spectrometry detects the difference in an isotope's mass, while infrared spectroscopy detects the difference in the isotope's vibrational modes. Nuclear magnetic resonance ...
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Biochemical Systems Theory
Biochemical systems theory is a mathematical modelling framework for biochemical systems, based on ordinary differential equations (ODE), in which biochemical processes are represented using power-law expansions in the variables of the system. This framework, which became known as Biochemical Systems Theory, has been developed since the 1960s by Michael Savageau, Eberhard Voit and others for the systems analysis of biochemical processes. According to Cornish-Bowden (2007) they "regarded this as a general theory of metabolic control, which includes both metabolic control analysis and flux-oriented theory as special cases". Athel Cornish-BowdenMetabolic control analysis FAQ website 18 April 2007. Representation The dynamics of a species is represented by a differential equation with the structure: \frac=\sum_j \mu_ \cdot \gamma_j \prod_k X_k^\, where ''X''''i'' represents one of the ''n''''d'' variables of the model (metabolite concentrations, protein concentrations or levels ...
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Metabolic Control Analysis
In biochemistry, metabolic control analysis (MCA) is a mathematical framework for describing Metabolic pathway, metabolic, Cell signaling#Signaling pathways, signaling, and genetic pathways. MCA quantifies how variables, such as fluxes and Chemical species, species concentrations, depend on Network (mathematics), network parameters. In particular, it is able to describe how network-dependent properties, called control coefficients, depend on Local property, local properties called Elasticity of a function, elasticities or elasticity coefficients. MCA was originally developed to describe the control in metabolic pathways but was subsequently extended to describe signaling and Gene regulatory network, genetic networks. MCA has sometimes also been referred to as ''Metabolic Control Theory,'' but this terminology was rather strongly opposed by Henrik Kacser, one of the founders. More recent work has shown that MCA can be Isomorphism, mapped directly on to classical control theory an ...
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