Metabolic Flux Analysis

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Questions and Answers

What is the primary module of metabolic networks that constitutes the major building blocks of most metabolic networks?

Branched pathway (correct)

Linear pathway

Stoichiometric matrix

Metabolic flux

What determines the overall distribution of metabolic fluxes in most biological systems?

Stoichiometric modeling framework

Extracellular metabolite concentration rates

Splitting ratios of branching fluxes at key nodes (correct)

Stressors on metabolism

What is used to derive comprehensive metabolic flux maps in metabolic flux analysis (MFA)?

Stoichiometric mass balance analysis (correct)

Feedback inhibition

Flux distribution

Extracellular metabolite concentration rates

What is the basic idea used to calculate flux distribution in metabolic flux analysis (MFA)?

Stoichiometric mass balance analysis Signup and view all the answers

What is used to represent the flow of metabolites in and out of the cell in metabolic network reconstruction?

Exchange reactions Signup and view all the answers

At steady state, the flux through each reaction is given by which equation?

$Sv = 0$ Signup and view all the answers

What is used to identify a flux distribution that maximizes or minimizes an objective function within the space of allowable fluxes in metabolic flux analysis?

Linear programming Signup and view all the answers

What is considered a gold standard for accurate and precise flux information in metabolic flux analysis?

13C-MFA Signup and view all the answers

What must be written to constrain metabolic fluxes in techniques like Flux Balance Analysis (FBA) and constraint-based reconstruction and analysis (COBRA)?

Stoichiometric matrix Signup and view all the answers

Which type of experiments can be used to infer metabolic flux in metabolic flux analysis?

Tracer experiments Signup and view all the answers

What is the primary purpose of a biomass reaction in metabolic network reconstruction?

Incorporating growth into the reconstruction Signup and view all the answers

Which method is used for quantifying metabolic fluxes in biological systems and requires no 13C-labeling experiments?

Flux Balance Analysis (FBA) Signup and view all the answers

What is used to synthesize tracer data in 13C-MFA?

Computational models Signup and view all the answers

What is used to reach the best global fit for flux estimation in metabolic flux analysis?

Computational programs Signup and view all the answers

What is proposed if the solution for flux estimation in metabolic flux analysis is not optimal?

Further labeling experiments Signup and view all the answers

What is used to define a system of linear equations with multiple possible solutions in metabolic flux analysis at steady state?

Stoichiometric matrix Signup and view all the answers

Study Notes

Metabolic Flux Analysis and Tracer Experiments

Metabolic fluxes can be described by mass balances of internal metabolites using the vector of metabolite concentrations (X), flux distribution vector (v), and stoichiometric matrix (S).
The stoichiometric matrix for Metabolite Balancing in MFA is constructed according to material balance equations.
A metabolic network reconstruction consists of stoichiometrically balanced biochemical reactions, represented in a matrix labeled S, with rows for metabolites and columns for reactions.
Growth is incorporated into the reconstruction with a biomass reaction, and exchange reactions are used to represent the flow of metabolites in and out of the cell.
At steady state, the flux through each reaction is given by Sv = 0, defining a system of linear equations with multiple possible solutions.
Linear programming is used to identify a flux distribution that maximizes or minimizes an objective function within the space of allowable fluxes defined by mass balance equations and reaction bounds.
Tracer experiments, MS, and NMR can be used to infer metabolic flux through the use of isotopic tracers, with 13C-MFA considered a gold standard for accurate and precise flux information.
The workflow for 13C-MFA involves designing an optimal tracer experiment, measuring metabolite labeling, synthesizing tracer data using computational models, and reaching the best global fit for flux estimation.
Classic MFA, Flux Balance Analysis (FBA), and constraint-based reconstruction and analysis (COBRA) methods are other techniques for quantifying metabolic fluxes in biological systems.
These techniques require no 13C-labeling experiments and involve fewer experimental data, but to constrain metabolic fluxes, the stoichiometric matrix for the given reaction networks must be written.
Computational programs help reach the best global fit for flux estimation, followed by statistical analysis to evaluate the fit, and further labeling experiments could be proposed if the solution is not optimal.
Key references for metabolic flux analysis include works by de Falco et al. (2022), Emwas et al. (2022), Kwilas et al. (2015), and Nielsen (2014), as well as the study by Orth et al. (2010) on flux balance analysis.

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Test your knowledge of Metabolic Flux Analysis and Tracer Experiments with this quiz. Explore concepts such as mass balances, stoichiometric matrix construction, use of isotopic tracers, computational modeling, and techniques like 13C-MFA, FBA, and COBRA.