@article{SteuerGrossSelbigetal.2006,
  author    = {Steuer, Ralf and Gross, Thilo and Selbig, Joachim and Blasius, Bernd},
  title     = {Structural kinetic modeling of metabolic networks},
  series = {Proceedings of the National Academy of Sciences of the United States of America},
  volume    = {103},
  journal   = {Proceedings of the National Academy of Sciences of the United States of America},
  number    = {32},
  publisher = {National Academy of Sciences},
  address   = {Washington},
  issn      = {0027-8424},
  doi       = {10.1073/pnas.0600013103},
  pages     = {11868 -- 11873},
  year      = {2006},
  abstract  = {To develop and investigate detailed mathematical models of metabolic processes is one of the primary challenges in systems biology. However, despite considerable advance in the topological analysis of metabolic networks, kinetic modeling is still often severely hampered by inadequate knowledge of the enzyme-kinetic rate laws and their associated parameter values. Here we propose a method that aims to give a quantitative account of the dynamical capabilities of a metabolic system, without requiring any explicit information about the functional form of the rate equations. Our approach is based on constructing a local linear model at each point in parameter space, such that each element of the model is either directly experimentally accessible or amenable to a straightforward biochemical interpretation. This ensemble of local linear models, encompassing all possible explicit kinetic models, then allows for a statistical exploration of the comprehensive parameter space. The method is exemplified on two paradigmatic metabolic systems: the glycolytic pathway of yeast and a realistic-scale representation of the photosynthetic Calvin cycle.},
  language  = {en}
}
@article{KartalMahlowSkupinetal.2011,
  author    = {Kartal, Oender and Mahlow, Sebastian and Skupin, Alexander and Ebenhoeh, Oliver},
  title     = {Carbohydrate-active enzymes exemplify entropic principles in metabolism},
  series = {Molecular systems biology},
  volume    = {7},
  journal   = {Molecular systems biology},
  number    = {10},
  publisher = {Nature Publ. Group},
  address   = {New York},
  issn      = {1744-4292},
  doi       = {10.1038/msb.2011.76},
  pages     = {11},
  year      = {2011},
  abstract  = {Glycans comprise ubiquitous and essential biopolymers, which usually occur as highly diverse mixtures. The myriad different structures are generated by a limited number of carbohydrate-active enzymes (CAZymes), which are unusual in that they catalyze multiple reactions by being relatively unspecific with respect to substrate size. Existing experimental and theoretical descriptions of CAZyme-mediated reaction systems neither comprehensively explain observed action patterns nor suggest biological functions of polydisperse pools in metabolism. Here, we overcome these limitations with a novel theoretical description of this important class of biological systems in which the mixing entropy of polydisperse pools emerges as an important system variable. In vitro assays of three CAZymes essential for central carbon metabolism confirm the power of our approach to predict equilibrium distributions and non-equilibrium dynamics. A computational study of the turnover of the soluble heteroglycan pool exemplifies how entropy-driven reactions establish a metabolic buffer in vivo that attenuates fluctuations in carbohydrate availability. We argue that this interplay between energy- and entropy-driven processes represents an important regulatory design principle of metabolic systems.},
  language  = {en}
}
@article{AraujoNunesNesiNikoloskietal.2012,
  author    = {Araujo, Wagner L. and Nunes-Nesi, Adriano and Nikoloski, Zoran and Sweetlove, Lee J. and Fernie, Alisdair R.},
  title     = {Metabolic control and regulation of the tricarboxylic acid cycle in photosynthetic and heterotrophic plant tissues},
  series = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology},
  volume    = {35},
  journal   = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology},
  number    = {1},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0140-7791},
  doi       = {10.1111/j.1365-3040.2011.02332.x},
  pages     = {1 -- 21},
  year      = {2012},
  abstract  = {The tricarboxylic acid (TCA) cycle is a crucial component of respiratory metabolism in both photosynthetic and heterotrophic plant organs. All of the major genes of the tomato TCA cycle have been cloned recently, allowing the generation of a suite of transgenic plants in which the majority of the enzymes in the pathway are progressively decreased. Investigations of these plants have provided an almost complete view of the distribution of control in this important pathway. Our studies suggest that citrate synthase, aconitase, isocitrate dehydrogenase, succinyl CoA ligase, succinate dehydrogenase, fumarase and malate dehydrogenase have control coefficients flux for respiration of -0.4, 0.964, -0.123, 0.0008, 0.289, 0.601 and 1.76, respectively; while 2-oxoglutarate dehydrogenase is estimated to have a control coefficient of 0.786 in potato tubers. These results thus indicate that the control of this pathway is distributed among malate dehydrogenase, aconitase, fumarase, succinate dehydrogenase and 2-oxoglutarate dehydrogenase. The unusual distribution of control estimated here is consistent with specific non-cyclic flux mode and cytosolic bypasses that operate in illuminated leaves. These observations are discussed in the context of known regulatory properties of the enzymes and some illustrative examples of how the pathway responds to environmental change are given.},
  language  = {en}
}