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Network analysis of intermediary metabolism using linear optimization. I. Development of mathematical formalism.

Joanne M. Savinell, +1 more
- 21 Feb 1992 - 
- Vol. 154, Iss: 4, pp 421-454
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TLDR
Analysis of metabolic networks using linear optimization theory allows one to quantify and understand the limitations imposed on the cell by its metabolic stoichiometry, and to understand how the flux through each pathway influences the overall behavior of metabolism.
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This article is published in Journal of Theoretical Biology.The article was published on 1992-02-21 and is currently open access. It has received 255 citations till now.

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Citations
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A protocol for generating a high-quality genome-scale metabolic reconstruction.

TL;DR: This protocol provides a helpful manual for all stages of the reconstruction process and presents a comprehensive protocol describing each step necessary to build a high-quality genome-scale metabolic reconstruction.
Journal ArticleDOI

Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110.

TL;DR: A predictive algorithm is formulated in order to apply the flux balance model to describe unsteady-state growth and by-product secretion in aerobic batch, fed-batch, and anaerobic batch cultures.
Journal ArticleDOI

Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use

TL;DR: The flux balance methodology allows the quantitative interpretation of metabolic physiology, gives an interpretation of experimental data, provides a guide to metabolic engineering, enables optimal medium formulation, and provides a method for bioprocess optimization.
Journal ArticleDOI

Non-linear optimization of biochemical pathways: applications to metabolic engineering and parameter estimation.

TL;DR: A generic approach to combine numerical optimization methods with biochemical kinetic simulations is described, suitable for use in the rational design of improved metabolic pathways with industrial significance and for solving the inverse problem of metabolic pathways.
Journal ArticleDOI

The biomass objective function

TL;DR: Fundamental issues associated with its formulation and use are reviewed and use to compute optimal growth states are reviewed.
References
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Branch point control by the phosphorylation state of isocitrate dehydrogenase. A quantitative examination of fluxes during a regulatory transition.

TL;DR: The modulation of protein phosphorylation and metabolite levels is one of the regulatory mechanisms which enables the bacterium to make dramatic shifts between metabolic pathways within a fraction of a doubling time.
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Mitochondrial-Cytosolic Interactions in Perfused Rat Heart ROLE OF COUPLED TRANSAMINATION IN REPLETION OF CITRIC ACID CYCLE INTERMEDIATES

TL;DR: It is postulated that changes in the tissue content of citric acid cycle intermediates and free amino acids in the heart during the transition from substrate-free perfusion to perfusion with medium containing 5 mm glucose and 5 x 10-3 units of insulin are a direct consequence of the regulation of glutamate influx across the mitochondrial membrane.
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Changes in RNA metabolism and accumulation of presumptive messenger RNA during transition from the growing to the quiescent state of cultured mouse fibroblasts.

TL;DR: Mouse fibroblasts maintained in tissue culture regulate total protein and ribosomal RNA synthesis co-ordinately with changes in the cellular growth state, and experiments suggest that the early increase in protein synthetic activity when quiescent, cultured cells are induced to grow is partially caused by an increased attachment of pre-existing mRNA molecules to free ribosomes.
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The ATP-to-oxygen stoichiometries of oxidative phosphorylation by rat liver mitochondria. An analysis of ADP-induced oxygen jumps by linear nonequilibrium thermodynamics.

TL;DR: In rat liver mitochondria, ADP/O ratios were determined from the total and extra oxygen consumed during ADP-stimulated respiration under conditions of quantitative conversion of ADP to ATP and suggest a new 13-proton scheme of chemiosmotic coupling in which proton stoichiometries are 5, 4, and 4 for Sites 1, 2, and 3.
Journal ArticleDOI

Effects of dissolved oxygen on hybridoma cell growth, metabolism, and antibody production kinetics in continuous culture.

TL;DR: Cell growth and viability, carbohydrate, amino acid, and energy metabolism, oxygen uptake, and antibody production rates were investigated, andCell growth was inhibited at both high and low DO, and cell viability was higher at low DO.
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Linear optimization theory is a mathematical formalism used to analyze metabolic networks and understand the limitations and behavior of metabolism.