Papers by Albert Sorribas
Journal of Biological Systems, Mar 1, 1995
Mathematical models are useful for analyzing metabolic problems. To build up these models, we nee... more Mathematical models are useful for analyzing metabolic problems. To build up these models, we need: (1) A scheme of the target system, (2) Measurements of concentrations and fluxes in steady-state, (3) The rate law of each reaction and (4) The set of differential equations that reflects the model behaviour. Usually, the rate-laws are identified from in vitro data, which could result in unrealistic models when compared with the behavior of the intact system. Hence, mathematical models must be carefully validated before one can trust their behavior. We can use different features of a biological system as a reference for validating a model. The steady-state robustness to parameter changes can be used as an index for such an evaluation. In this sense, a realistic model should reflect a fundamental property of a living system: small perturbations are compatible with system performance. We present an example of such analysis in the case of the ethanolic fermentation pathway of Saccharomyces cerevisiae. The parameter sensitivities of the model are computed in two experimental conditions and a diagnostic is made on the validity of the corresponding model. Translation of the mechanistic model into an S-system model facilitates the analysis of parameter sensitivity. After the analysis, a high parameter sensitivity suggest the need for a careful estimation of the involved parameters.
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Journal of Theoretical Medicine, 1999
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Springer eBooks, 1993
A main objective in investigating a metabolic pathway is to obtain a definite idea of both its st... more A main objective in investigating a metabolic pathway is to obtain a definite idea of both its structure, in terms of material and information relationships, and its behavior. Traditionally, the schematic representation of a given pathway is based on previous information mainly obtained by experiments in vitro. Measurements on the intact system are then used for testing the resulting structure. This is justified by the idea that knowing the elements of a given pathway will lead us to a deep understanding of both its properties and its behavior under specified conditions. However, there is now increasing evidence that complete characterization of each element in vitro does not necessarily lead to a correct description of the whole system1–4. In practice, and especially if we consider the relevant regulatory signals within the system, it is often difficult to agree on a single scheme, and different possibilities arise. On one hand, the in situ conditions can make it some of the effects shown in vitro irrelevant. On the other hand, it is possible that some interactions not shown in vitro could be of interest in situ. Hence, we are dealing with a situation close to a black box, in the sense that the relationships within the system are not clearly established.
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Mathematical and Computer Modelling, 1988
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De Gruyter eBooks, Dec 31, 1996
ABSTRACT
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Elsevier eBooks, 2009
In this paper, we present a new method that is able of identifying the optimal enzyme activity ch... more In this paper, we present a new method that is able of identifying the optimal enzyme activity changes that allow a system to meet a set of physiological constraints. The problem is formulated as a nonlinear programming (NLP) model, and it is solved by a novel bi-level global optimization algorithm that exploits its mathematical structure.
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Biometrical Journal, Dec 1, 2001
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BMC Bioinformatics, Nov 24, 2009
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Mathematical biosciences, Nov 1, 1995
Mathematical tools that involve the determination of systemic responses to small changes in metab... more Mathematical tools that involve the determination of systemic responses to small changes in metabolites or enzymes have demonstrated their utility for analyzing metabolic pathways. The different methodologies based on these ideas allow for modeling and analyzing biochemical pathways focusing on the coordinate behavior of the whole system. However, one must become familiar with the difference in nomenclature and methodology to relate the models and results obtained by applying these techniques and to appreciate their potential for answering fundamental questions about biochemical systems. In the following three papers we show how this can be facilitated by comparing the nomenclature, methodology, and results of the two leading techniques in this area, metabolic control analysis and biochemical systems theory, using a model of the fermentation pathway in Saccharomyces cerevisiae as a reference system. In the present paper we review the nomenclature, technical concepts, and related experimental measurements while creating a practical dictionary for the reference system that makes the relatedness of the two approaches more apparent. In the second paper, subtitled Steady-State Analysis, we show that both approaches give the same picture for many systemic responses of the reference system. In the third paper of this series, subtitled Model Validation and Dynamic Behavior, we show that the quality of the model can be assessed by studying the sensitivity to changes in the system parameters. We hope to illustrate the usefulness of these tools in providing an interpretation of the experimental measurements in a specific metabolic pathway.
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Mathematical biosciences, Jun 1, 1989
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Mathematical biosciences, Nov 1, 1995
Mathematical tools that involve the determination of systemic responses to small changes in metab... more Mathematical tools that involve the determination of systemic responses to small changes in metabolites or enzymes have demonstrated their utility for analyzing metabolic pathways. The different methodologies based on these ideas allow for modeling and analyzing biochemical pathways focusing on the coordinate behavior of the whole system. However, one must become familiar with the difference in nomenclature and methodology to relate the models and results obtained by applying these techniques and to appreciate their potential for answering fundamental questions about biochemical systems. In the following three papers we show how this can be facilitated by comparing the nomenclature, methodology, and results of the two leading techniques in this area, metabolic control analysis and biochemical systems theory, using a model of the fermentation pathway in Saccharomyces cerevisiae as a reference system. In the present paper we review the nomenclature, technical concepts, and related experimental measurements while creating a practical dictionary for the reference system that makes the relatedness of the two approaches more apparent. In the second paper, subtitled Steady-State Analysis, we show that both approaches give the same picture for many systemic responses of the reference system. In the third paper of this series, subtitled Model Validation and Dynamic Behavior, we show that the quality of the model can be assessed by studying the sensitivity to changes in the system parameters. We hope to illustrate the usefulness of these tools in providing an interpretation of the experimental measurements in a specific metabolic pathway.
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Trends in Biochemical Sciences, 1987
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Mathematical biosciences, Nov 1, 1995
Mathematical tools that involve the determination of systemic responses to small changes in metab... more Mathematical tools that involve the determination of systemic responses to small changes in metabolites or enzymes have demonstrated their utility for analyzing metabolic pathways. The different methodologies based on these ideas allow for modeling and analyzing biochemical pathways focusing on the coordinate behavior of the whole system. However, one must become familiar with the difference in nomenclature and methodology to relate the models and results obtained by applying these techniques and to appreciate their potential for answering fundamental questions about biochemical systems. In the following three papers we show how this can be facilitated by comparing the nomenclature, methodology, and results of the two leading techniques in this area, metabolic control analysis and biochemical systems theory, using a model of the fermentation pathway in Saccharomyces cerevisiae as a reference system. In the present paper we review the nomenclature, technical concepts, and related experimental measurements while creating a practical dictionary for the reference system that makes the relatedness of the two approaches more apparent. In the second paper, subtitled Steady-State Analysis, we show that both approaches give the same picture for many systemic responses of the reference system. In the third paper of this series, subtitled Model Validation and Dynamic Behavior, we show that the quality of the model can be assessed by studying the sensitivity to changes in the system parameters. We hope to illustrate the usefulness of these tools in providing an interpretation of the experimental measurements in a specific metabolic pathway.
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Mathematical biosciences, Jun 1, 1989
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Mathematical and Computer Modelling, Feb 1, 2000
ABSTRACT
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Frontiers in Plant Science
Many highly valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical in... more Many highly valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries belong to the terpenoid family. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using two alternative pathways: a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. As such, developing plants for use as a platform to use IPP/DMAPP and produce high value terpenoids is an important biotechnological goal. Still, IPP/DMAPP are the precursors to many plant developmental hormones. This creates severe challenges in redirecting IPP/DMAPP towards production of non-cognate plant metabolites. A potential solution to this problem is increasing the IPP/DMAPP production flux in planta. Here, we aimed at discovering, understanding, and predicting the effects of increasing IPP/DMAPP production in plants through modelling. We used sy...
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Frontiers in Plant Science, Sep 2, 2022
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PeerJ, 2021
Phosphorelays are signal transduction circuits that sense environmental changes and adjust cellul... more Phosphorelays are signal transduction circuits that sense environmental changes and adjust cellular metabolism. Five different circuit architectures account for 99% of all phosphorelay operons annotated in over 9,000 fully sequenced genomes. Here we asked what biological design principles, if any, could explain selection among those architectures in nature. We began by studying kinetically well characterized phosphorelays (Spo0 of Bacillus subtilis and Sln1 of Saccharomyces cerevisiae). We find that natural circuit architecture maximizes information transmission in both cases. We use mathematical models to compare information transmission among the architectures for a realistic range of concentration and parameter values. Mapping experimentally determined phosphorelay protein concentrations onto that range reveals that the native architecture maximizes information transmission in sixteen out of seventeen analyzed phosphorelays. These results suggest that maximization of information ...
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Papers by Albert Sorribas