Herrgård, Markus J., Swainston, Neil, Dobson, Paul, Dunn, Warwick B., Arga, K. Yalçin, Arvas, Mikko, ...
Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several...
Review TRENDS in Microbiology Vol.15 No.1 The nature of systems biology (2008)
Frank J. Bruggeman, Hans V. Westerhoff
The advent of functional genomics has enabled the molecular biosciences to come a long way towards characterizing the molecular constituents of life. Yet, the challenge for biology overall is to...
Herrgård, Markus J, Swainston, Neil, Dobson, Paul, Dunn, Warwick B, Arga, K Yalçin, Arvas, Mikko, ...
Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several...
Networks: A New Summation Law (2007)
M. A. Peletier, H. V. Westerhoff, B. N. Kholodenko, Mark A. Peletier, Hans V. Westerhoff, Boris N. Kholodenko
Control of spatially heterogeneous and time-varying cellular reaction networks: a new summation law
phosphotransferase system and the effect (2007)
Christof Francke, Hans V. Westerhoff, Joke G. Blom, Mark A. Peletier
control of the bacterial phosphoenolpyruvate:glucose
C. Francke, P. W. Postma, H. V. Westerhoff, J. G. Blom, M. A. Peletier, Christof Francke, ...
Why the phosphotransferase system of Escherichia coli escapes the diffusion limitation of signal transduction, transport and metabolism that confronts mammalian cells
Biochemistry Private Bag X1 (2007)
De Boelelaan A, Catholijn M. Jonker, Jacky L. Snoep, Hans V. Westerhoff
Existing chemical models of bacteria are complicated, due to the thousands of interacting chemical reactions within the cell. To gain models are needed. In this paper an intentional dynamic modelling...
Jorrit J. Hornberg, Frank J. Bruggeman, Bernd Binder, Christian R. Geest, Jan Lankelma, Reinhart Heinrich, ...
Principles behind the multifarious control of signal transduction
Peletier, Mark A., Westerhoff, Hans V., Kholodenko, Boris N.
A hallmark of a plethora of intracellular signaling pathways is the spatial separation of activation and deactivation processes that potentially results in precipitous gradients of activated...
Putting Intentions into Cell Biochemistry: An Artificial Intelligence Perspective (2002)
Catholijn M. Jonker, Jan Treur, Hans V. Westerhoff
The living cell exists by virtue ofthousands ofnonlinearly interacting processes. This complexity greatly impedes its understanding. The standard approach to the calculation ofthe behaviour ofthe...
Christof Francke, Hans V. Westerhoff, Mark A. Peletier
ABSTRACT We calculated the implications of diffusion for the phosphoenolpyruvate:glucose phosphotransferase system (glucose-PTS) of Escherichia coli in silicon cells of various magnitudes. For a cell...
Embodied Intentional Dynamics of Bacterial Behaviour (2001)
Catholijn M. Jonker, Jacky L. Snoep, Hans V. Westerhoff
Existing (embodied) chemical models of bacteria are rather complex, due to the thousands of interacting chemical reactions within the cell. To gain a higher level of understanding, more transparent...
Van Rotterdam, Bart J., Westerhoff, Hans V., Visschers, Ronald W., Jones, Michael R., Hellingwerf, Klaas J., Crielaard, Wim
The mechanism, thermodynamics and kinetics of light-induced cyclic electron transfer have been studied in a model energy-transducing system consisting of solubilized Rhodobacter sphaeroides reaction...
Bas Teusink, Jasper A. Diderich, Hans V. Westerhoff, Karel Van Dam, C. Walsh
In Saccharomyces cerevisiae cells exhibiting high-affinity glucose transport, the glucose consumption rate at extracellular concentrations above 10 mM was only half of the zero trans-influx rate. To...
Westerhoff, Hans V., Lolkema, Juke S., Otto, Roel, Hellingwerf, Klaas J.
Microbial growth is analyzed in terms of mosaic and phenomenological non-equilibrium thermodynamics. It turns out that already existing parameters devised to measure bacterial growth, such as YATP,...
Compartmentation protects trypanosomes from the dangerous design of glycolysis
Bakker, Barbara M., Mensonides, Femke I. C., Teusink, Bas, Van Hoek, Pim, Michels, Paul A. M., Westerhoff, Hans V.
Unlike in other organisms, in trypanosomes and other Kinetoplastida the larger part of glycolysis takes place in a specialized organelle, called the glycosome. At present it is impossible to remove...
Contribution of glucose transport to the control of the glycolytic flux in Trypanosoma brucei
Bakker, Barbara M., Walsh, Michael C., Ter Kuile, Benno H., Mensonides, Femke I. C., Michels, Paul A. M., Opperdoes, Fred R., ...
The rate of glucose transport across the plasma membrane of the bloodstream form of Trypanosoma brucei was modulated by titration of the hexose transporter with the inhibitor phloretin, and the...
Van Heeswijk, Wally C., Wen, Daying, Clancy, Paula, Jaggi, Rene, Ollis, David L., Westerhoff, Hans V., ...
The PII protein is Escherichia coli's cognate transducer of the nitrogen signal to the NRII (NtrB)/NRI (NtrC) two-component system and to adenylyltransferase. Through these two routes, PII regulates...
Implications of macromolecular crowding for signal transduction and metabolite channeling
Rohwer, Johann M., Postma, Pieter W., Kholodenko, Boris N., Westerhoff, Hans V.
The effect of different total enzyme concentrations on the flux through the bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) in vitro was determined by measuring...
Nitric Oxide Is a Signal for NNR-Mediated Transcription Activation in Paracoccus denitrificans
Houben, Edith, Reijnders, Willem N. M., Spiro, Stephen, Westerhoff, Hans V., Saunders, Neil
By using the ′lacZ gene, the activities of the nirI, nirS, and norC promoters were assayed in the wild type and in NNR-deficient mutants of Paracoccus denitrificans grown under various growth...
Ward, Donald E., Van Der Weijden, Coen C., Van Der Merwe, Marthinus J., Westerhoff, Hans V., Claiborne, Al, Snoep, Jacky L.
Recently the bkd gene cluster from Enterococcus faecalis was sequenced, and it was shown that the gene products constitute a pathway for the catabolism of branched-chain α-keto acids. We have now...
Saunders, Neil F. W., Hornberg, Jorrit J., Reijnders, Willem N. M., Westerhoff, Hans V., De Vries, Simon
The nos (nitrous oxide reductase) operon of Paracoccus denitrificans contains a nosX gene homologous to those found in the nos operons of other denitrifiers. NosX is also homologous to NirX, which is...
Otten, Marijke F., Van Der Oost, John, Reijnders, Willem N. M., Westerhoff, Hans V., Ludwig, Bernd
Paracoccus denitrificans strains with mutations in the genes encoding the cytochrome c550, c552, or c1 and in combinations of these genes were constructed, and their growth characteristics were...
Autoamplification of a Two-Component Regulatory System Results in “Learning” Behavior
Hoffer, Sally M., Westerhoff, Hans V., Hellingwerf, Klaas J., Postma, Pieter W., Tommassen, Jan
We have tested the hypothesis that the autoamplification of two-component regulatory systems results in “learning” behavior, i.e., that bacteria respond faster or more extensively to a signal...
Teusink, Bas, Diderich, Jasper A., Westerhoff, Hans V., Van Dam, Karel, Walsh, Michael C.
In Saccharomyces cerevisiae cells exhibiting high-affinity glucose transport, the glucose consumption rate at extracellular concentrations above 10 mM was only half of the zero trans-influx rate. To...
Ortega, Fernando, Acerenza, Luis, Westerhoff, Hans V., Mas, Francesc, Cascante, Marta
Covalent modification cycles are ubiquitous. Theoretical studies have suggested that they serve to increase sensitivity. However, this suggestion has not been corroborated experimentally in vivo....
Untangling the wires: A strategy to trace functional interactions in signaling and gene networks
Kholodenko, Boris N., Kiyatkin, Anatoly, Bruggeman, Frank J., Sontag, Eduardo, Westerhoff, Hans V., Hoek, Jan B.
Emerging technologies have enabled the acquisition of large genomics and proteomics data sets. However, current methodologies for analysis do not permit interpretation of the data in ways that...
Beaumont, Hubertus J. E., Hommes, Norman G., Sayavedra-Soto, Luis A., Arp, Daniel J., Arciero, David M., Hooper, Alan B., ...
A gene that encodes a periplasmic copper-type nitrite reductase (NirK) was identified in Nitrosomonas europaea. Disruption of this gene resulted in the disappearance of Nir activity in cell extracts....
The Glycolytic Flux in Escherichia coli Is Controlled by the Demand for ATP
Koebmann, Brian J., Westerhoff, Hans V., Snoep, Jacky L., Nilsson, Dan, Jensen, Peter R.
The nature of the control of glycolytic flux is one of the central, as-yet-uncharacterized issues in cellular metabolism. We developed a molecular genetic tool that specifically induces ATP...
Thermodynamic efficiency of microbial growth is low but optimal for maximal growth rate
Westerhoff, Hans V., Hellingwerf, Klaas J., Van Dam, Karel
Thermodynamic efficiency of microbial growth on substrates that are more oxidized than biomass approaches 24%. This is the theoretical value for a linear energy converter optimized for maximal output...
Nitrosomonas europaea Expresses a Nitric Oxide Reductase during Nitrification
Beaumont, Hubertus J. E., Van Schooten, Bas, Lens, Sylvia I., Westerhoff, Hans V.
In this paper, we report the identification of a norCBQD gene cluster that encodes a functional nitric oxide reductase (Nor) in Nitrosomonas europaea. Disruption of the norB gene resulted in a...
Beaumont, Hubertus J. E., Lens, Sylvia I., Westerhoff, Hans V.
Nitrite reductase (NirK) of Nitrosomonas europaea confers tolerance to nitrite (NO2−). The nirK gene is clustered with three genes of unknown physiological function: ncgABC. At present, this...
Lin, Bin, Braster, Martin, Van Breukelen, Boris M., Van Verseveld, Henk W., Westerhoff, Hans V., Röling, Wilfred F. M.
Relationships between community composition of the iron-reducing Geobacteraceae, pollution levels, and the occurrence of biodegradation were established for an iron-reducing aquifer polluted with...
Control analysis for autonomously oscillating biochemical networks.
Reijenga, Karin A, Westerhoff, Hans V, Kholodenko, Boris N, Snoep, Jacky L
It has hitherto not been possible to analyze the control of oscillatory dynamic cellular processes in other than qualitative ways. The control coefficients, used in metabolic control analyses of...
Why the Phosphotransferase System of Escherichia coli Escapes Diffusion Limitation
Francke, Christof, Postma, Pieter W., Westerhoff, Hans V., Blom, Joke G., Peletier, Mark A.
We calculated the implications of diffusion for the phosphoenolpyruvate:glucose phosphotransferase system (glucose-PTS) of Escherichia coli in silicon cells of various magnitudes. For a cell of...
Brady, Nathan R., Elmore, Steven P., Krab, Klaas, Courtoy, Pierre J., Hue, Louis, ...
Reactive oxygen species (ROS) can trigger a transient burst of mitochondrial ROS production via ROS activation of the mitochondrial permeability transition pore (MPTP), a phenomenon termed...
Rossell, Sergio, Van Der Weijden, Coen C., Lindenbergh, Alexander, Van Tuijl, Arjen, Francke, Christof, Bakker, Barbara M., ...
An important question is to what extent metabolic fluxes are regulated by gene expression or by metabolic regulation. There are two distinct aspects to this question: (i) the local regulation of the...
Compartmentation protects trypanosomes from the dangerous design of glycolysis
Bakker, Barbara M., Mensonides, Femke I. C., Teusink, Bas, Van Hoek, Pim, Michels, Paul A. M., Westerhoff, Hans V.
Unlike in other organisms, in trypanosomes and other Kinetoplastida the larger part of glycolysis takes place in a specialized organelle, called the glycosome. At present it is impossible to remove...
Contribution of glucose transport to the control of the glycolytic flux in Trypanosoma brucei
Bakker, Barbara M., Walsh, Michael C., Ter Kuile, Benno H., Mensonides, Femke I. C., Michels, Paul A. M., Opperdoes, Fred R., ...
The rate of glucose transport across the plasma membrane of the bloodstream form of Trypanosoma brucei was modulated by titration of the hexose transporter with the inhibitor phloretin, and the...
Van Heeswijk, Wally C., Wen, Daying, Clancy, Paula, Jaggi, Rene, Ollis, David L., Westerhoff, Hans V., ...
The PII protein is Escherichia coli's cognate transducer of the nitrogen signal to the NRII (NtrB)/NRI (NtrC) two-component system and to adenylyltransferase. Through these two routes, PII regulates...
Implications of macromolecular crowding for signal transduction and metabolite channeling
Rohwer, Johann M., Postma, Pieter W., Kholodenko, Boris N., Westerhoff, Hans V.
The effect of different total enzyme concentrations on the flux through the bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) in vitro was determined by measuring...
Nitric Oxide Is a Signal for NNR-Mediated Transcription Activation in Paracoccus denitrificans
Houben, Edith, Reijnders, Willem N. M., Spiro, Stephen, Westerhoff, Hans V., Saunders, Neil
By using the ′lacZ gene, the activities of the nirI, nirS, and norC promoters were assayed in the wild type and in NNR-deficient mutants of Paracoccus denitrificans grown under various growth...
Ward, Donald E., Van Der Weijden, Coen C., Van Der Merwe, Marthinus J., Westerhoff, Hans V., Claiborne, Al, Snoep, Jacky L.
Recently the bkd gene cluster from Enterococcus faecalis was sequenced, and it was shown that the gene products constitute a pathway for the catabolism of branched-chain α-keto acids. We have now...
Saunders, Neil F. W., Hornberg, Jorrit J., Reijnders, Willem N. M., Westerhoff, Hans V., De Vries, Simon
The nos (nitrous oxide reductase) operon of Paracoccus denitrificans contains a nosX gene homologous to those found in the nos operons of other denitrifiers. NosX is also homologous to NirX, which is...
Otten, Marijke F., Van Der Oost, John, Reijnders, Willem N. M., Westerhoff, Hans V., Ludwig, Bernd
Paracoccus denitrificans strains with mutations in the genes encoding the cytochrome c550, c552, or c1 and in combinations of these genes were constructed, and their growth characteristics were...
Autoamplification of a Two-Component Regulatory System Results in “Learning” Behavior
Hoffer, Sally M., Westerhoff, Hans V., Hellingwerf, Klaas J., Postma, Pieter W., Tommassen, Jan
We have tested the hypothesis that the autoamplification of two-component regulatory systems results in “learning” behavior, i.e., that bacteria respond faster or more extensively to a signal...
Teusink, Bas, Diderich, Jasper A., Westerhoff, Hans V., Van Dam, Karel, Walsh, Michael C.
In Saccharomyces cerevisiae cells exhibiting high-affinity glucose transport, the glucose consumption rate at extracellular concentrations above 10 mM was only half of the zero trans-influx rate. To...
Ortega, Fernando, Acerenza, Luis, Westerhoff, Hans V., Mas, Francesc, Cascante, Marta
Covalent modification cycles are ubiquitous. Theoretical studies have suggested that they serve to increase sensitivity. However, this suggestion has not been corroborated experimentally in vivo....
Untangling the wires: A strategy to trace functional interactions in signaling and gene networks
Kholodenko, Boris N., Kiyatkin, Anatoly, Bruggeman, Frank J., Sontag, Eduardo, Westerhoff, Hans V., Hoek, Jan B.
Emerging technologies have enabled the acquisition of large genomics and proteomics data sets. However, current methodologies for analysis do not permit interpretation of the data in ways that...
Beaumont, Hubertus J. E., Hommes, Norman G., Sayavedra-Soto, Luis A., Arp, Daniel J., Arciero, David M., Hooper, Alan B., ...
A gene that encodes a periplasmic copper-type nitrite reductase (NirK) was identified in Nitrosomonas europaea. Disruption of this gene resulted in the disappearance of Nir activity in cell extracts....
The Glycolytic Flux in Escherichia coli Is Controlled by the Demand for ATP
Koebmann, Brian J., Westerhoff, Hans V., Snoep, Jacky L., Nilsson, Dan, Jensen, Peter R.
The nature of the control of glycolytic flux is one of the central, as-yet-uncharacterized issues in cellular metabolism. We developed a molecular genetic tool that specifically induces ATP...
Thermodynamic efficiency of microbial growth is low but optimal for maximal growth rate
Westerhoff, Hans V., Hellingwerf, Klaas J., Van Dam, Karel
Thermodynamic efficiency of microbial growth on substrates that are more oxidized than biomass approaches 24%. This is the theoretical value for a linear energy converter optimized for maximal output...
Nitrosomonas europaea Expresses a Nitric Oxide Reductase during Nitrification
Beaumont, Hubertus J. E., Van Schooten, Bas, Lens, Sylvia I., Westerhoff, Hans V.
In this paper, we report the identification of a norCBQD gene cluster that encodes a functional nitric oxide reductase (Nor) in Nitrosomonas europaea. Disruption of the norB gene resulted in a...
Beaumont, Hubertus J. E., Lens, Sylvia I., Westerhoff, Hans V.
Nitrite reductase (NirK) of Nitrosomonas europaea confers tolerance to nitrite (NO2−). The nirK gene is clustered with three genes of unknown physiological function: ncgABC. At present, this...
Lin, Bin, Braster, Martin, Van Breukelen, Boris M., Van Verseveld, Henk W., Westerhoff, Hans V., Röling, Wilfred F. M.
Relationships between community composition of the iron-reducing Geobacteraceae, pollution levels, and the occurrence of biodegradation were established for an iron-reducing aquifer polluted with...
Control analysis for autonomously oscillating biochemical networks.
Reijenga, Karin A, Westerhoff, Hans V, Kholodenko, Boris N, Snoep, Jacky L
It has hitherto not been possible to analyze the control of oscillatory dynamic cellular processes in other than qualitative ways. The control coefficients, used in metabolic control analyses of...
Why the Phosphotransferase System of Escherichia coli Escapes Diffusion Limitation
Francke, Christof, Postma, Pieter W., Westerhoff, Hans V., Blom, Joke G., Peletier, Mark A.
We calculated the implications of diffusion for the phosphoenolpyruvate:glucose phosphotransferase system (glucose-PTS) of Escherichia coli in silicon cells of various magnitudes. For a cell of...
Brady, Nathan R., Elmore, Steven P., Krab, Klaas, Courtoy, Pierre J., Hue, Louis, ...
Reactive oxygen species (ROS) can trigger a transient burst of mitochondrial ROS production via ROS activation of the mitochondrial permeability transition pore (MPTP), a phenomenon termed...
Rossell, Sergio, Van Der Weijden, Coen C., Lindenbergh, Alexander, Van Tuijl, Arjen, Francke, Christof, Bakker, Barbara M., ...
An important question is to what extent metabolic fluxes are regulated by gene expression or by metabolic regulation. There are two distinct aspects to this question: (i) the local regulation of the...
Lloyd-Smith, James O., Getz, Wayne M., Westerhoff, Hans V.
We explore the transmission process for sexually transmitted diseases (STDs). We derive the classical frequency-dependent incidence mechanistically from a pair-formation model, using an approximation...
Daran-Lapujade, Pascale, Rossell, Sergio, Van Gulik, Walter M., Luttik, Marijke A. H., Slijper, Monique, ...
Metabolic fluxes may be regulated “hierarchically,” e.g., by changes of gene expression that adjust enzyme capacities (Vmax) and/or “metabolically” by interactions of enzymes with substrates,...
Recurrent design patterns in the feedback regulation of the mammalian signalling network
Legewie, Stefan, Herzel, Hanspeter, Westerhoff, Hans V, Blüthgen, Nils
Biochemical networks are characterized by recurrent patterns and motifs, but the design principles underlying the dynamics of the mammalian intracellular signalling network remain unclear. We...
Attractive Models: How to Make the Silicon Cell Relevant and Dynamic
Westerhoff, Hans V., Bruggeman, Frank, Hofmeyr, Jan-Hendrik S., Snoep, Jacky L.
Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes
Haanstra, Jurgen R., Van Tuijl, Arjen, Kessler, Peter, Reijnders, Willem, Michels, Paul A. M., Westerhoff, Hans V., ...
ATP generation by both glycolysis and glycerol catabolism is autocatalytic, because the first kinases of these pathways are fuelled by ATP produced downstream. Previous modeling studies predicted...
Monkhorst, Kim, De Hoon, Bas, Jonkers, Iris, Mulugeta Achame, Eskeatnaf, Monkhorst, Wouter, Hoogerbrugge, Jos, ...
Noise Management by Molecular Networks
Bruggeman, Frank J., Blüthgen, Nils, Westerhoff, Hans V.
Fluctuations in the copy number of key regulatory macromolecules (“noise”) may cause physiological heterogeneity in populations of (isogenic) cells. The kinetics of processes and their wiring in...