Dynamic Optimal Control of Homeostasis: An Integrative System Approach for Modeling of the Central Nitrogen Metabolism in Saccharomyces cerevisiae

Riel, van Naw Natal; Giuseppin, Mlf; Verrips, C. Theo

doi:10.1006/mben.1999.0137

Cited by 19 publications

(15 citation statements)

References 28 publications

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“…In the future the complexity will even increase, when biosciences will concentrate not just on the molecules but also on their intracellular localization as a function of time after a certain event. To understand the interrelation of molecules quantitatively it is necessary to develop structural and/or cybernetic models that describe even subtle di¡erences in regulatory and metabolic processes [91,123]. Such models are a prerequisite for understanding diseases related to malfunctions of the metabolism of humans, to understand better the bene¢cial in£uence of certain components of foods on human health and reprogramming metabolisms of organisms to increase their industrial utility.…”

Section: A Model Describing Ncr Regulation On Transcriptionmentioning

confidence: 99%

The role of ammonia metabolism in nitrogen catabolite repression in Saccharomyces cerevisiae

Schure¹

2000

FEMS Microbiology Reviews

123

159

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Saccharomyces cerevisiae is able to use a wide variety of nitrogen sources for growth. Not all nitrogen sources support growth equally well. In order to select the best out of a large diversity of available nitrogen sources, the yeast has developed molecular mechanisms. These mechanisms consist of a sensing mechanism and a regulatory mechanism which includes induction of needed systems, and repression of systems that are not beneficial. The first step in use of most nitrogen sources is its uptake via more or less specific permeases. Hence the first level of regulation is encountered at this level. The next step is the degradation of the nitrogen source to useful building blocks via the nitrogen metabolic pathways. These pathways can be divided into routes that lead to the degradation of the nitrogen source to ammonia and glutamate, and routes that lead to the synthesis of nitrogen containing compounds in which glutamate and glutamine are used as nitrogen donor. Glutamine is synthesized out of ammonia and glutamate. The expression of the specific degradation routes is also regulated depending on the availability of a particular nitrogen source. Ammonia plays a central role as intermediate between degradative and biosynthetic pathways. It not only functions as a metabolite in metabolic reactions but is also involved in regulation of metabolic pathways at several levels. This review describes the central role of ammonia in nitrogen metabolism. This role is illustrated at the level of enzyme activity, translation and transcription.

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Section: A Model Describing Ncr Regulation On Transcriptionmentioning

confidence: 99%

The role of ammonia metabolism in nitrogen catabolite repression in Saccharomyces cerevisiae

Schure¹

2000

FEMS Microbiology Reviews

123

159

View full text Add to dashboard Cite

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“…To date, there have been relatively few studies on dynamic optimization of metabolic pathways (as observed in Torres and Voit, 2002, p. 165). In Varner and Ramkrishna (1999), the authors develop a theoretical framework where cells are regarded as optimal resource allocators following cybernetic principles, while extensions of the FBA principle to include dynamic behavior have been reported in a number of works (van Riel et al, 2000;Mahadevan et al, 2002;Uygun et al, 2006). Dynamic enzyme optimization for the activation of biosynthetic pathways has been considered recently in Klipp et al (2002) and Zaslaver et al (2004).…”

Section: Introductionmentioning

confidence: 99%

Sequential Activation of Metabolic Pathways: a Dynamic Optimization Approach

et al. 2009

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The regulation of cellular metabolism facilitates robust cellular operation in the face of changing external conditions. The cellular response to this varying environment may include the activation or inactivation of appropriate metabolic pathways. Experimental and numerical observations of sequential timing in pathway activation have been reported in the literature. It has been argued that such patterns can be rationalized by means of an underlying optimal metabolic design. In this paper we pose a dynamic optimization problem that accounts for time-resource minimization in pathway activation under constrained total enzyme abundance. The optimized variables are time-dependent enzyme concentrations that drive the pathway to a steady state characterized by a prescribed metabolic flux. The problem formulation addresses unbranched pathways with irreversible kinetics. Neither specific reaction kinetics nor fixed pathway length are assumed.In the optimal solution, each enzyme follows a switching profile between zero and maximum concentration, following a temporal sequence that matches the pathway topology. This result provides an analytic justification of the sequential activation previously described in the literature. In contrast with the existent numerical approaches, the activation sequence is proven to be optimal for a generic class of monomolecular kinetics. This class includes, but is not limited to, Mass Action, Michaelis-Menten, Hill, and some Power-law models. This suggests that sequential enzyme expression may be a common feature of metabolic regulation, as it is a robust property of optimal pathway activation.

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“…Mathematical models of central nitrogen metabolism have recently been constructed [13,14], based on previous data [15^17] from nitrogen-limited continuous cultures. In a mechanistic model [13] metabolic control was implemented as Michaelis^Menten enzyme kinetics.…”

Section: Introductionmentioning

confidence: 99%

The glutamate synthase (GOGAT) of plays an important role in central nitrogen metabolism

Guillamón

Vanriel

Giuseppin³

et al. 2001

FEMS Yeast Research

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Dynamic Optimal Control of Homeostasis: An Integrative System Approach for Modeling of the Central Nitrogen Metabolism in Saccharomyces cerevisiae

Cited by 19 publications

References 28 publications

The role of ammonia metabolism in nitrogen catabolite repression in Saccharomyces cerevisiae

The role of ammonia metabolism in nitrogen catabolite repression in Saccharomyces cerevisiae

Sequential Activation of Metabolic Pathways: a Dynamic Optimization Approach

The glutamate synthase (GOGAT) of plays an important role in central nitrogen metabolism

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