89,213 research outputs found
Chemical Basis of Metabolic Network Organization
Although the metabolic networks of the three domains of life consist of different constituents and metabolic pathways, they exhibit the same scale-free organization. This phenomenon has been hypothetically explained by preferential attachment principle that the new-recruited metabolites attach preferentially to those that are already well connected. However, since metabolites are usually small molecules and metabolic processes are basically chemical reactions, we speculate that the metabolic network organization may have a chemical basis. In this paper, chemoinformatic analyses on metabolic networks of Kyoto Encyclopedia of Genes and Genomes (KEGG), Escherichia coli and Saccharomyces cerevisiae were performed. It was found that there exist qualitative and quantitative correlations between network topology and chemical properties of metabolites. The metabolites with larger degrees of connectivity (hubs) are of relatively stronger polarity. This suggests that metabolic networks are chemically organized to a certain extent, which was further elucidated in terms of high concentrations required by metabolic hubs to drive a variety of reactions. This finding not only provides a chemical explanation to the preferential attachment principle for metabolic network expansion, but also has important implications for metabolic network design and metabolite concentration prediction
Towards a Model of Life and Cognition
What should be the ontology of the world such that life and cognition are possible? In this essay, I undertake to outline an alternative ontological foundation which makes biological and cognitive phenomena possible. The foundation is built by defining a model, which is presented in the form of a description of a hypothetical but a logically possible world with a defined ontological base.
Biology rests today on quite a few not so well connected foundations: molecular biology based on the genetic dogma; evolutionary biology based on neo-Darwinian model; ecology based on systems view; developmental biology by morphogenetic models; connectionist models for neurophysiology and cognitive biology; pervasive teleonomic
explanations for the goal-directed behavior across the discipline; etc. Can there be an underlying connecting theme or a model which could make these seemingly disparate domains interconnected? I shall atempt to answer this question.
By following the semantic view of scientific theories, I tend to believe that the models employed by the present physical sciences are not rich enough to capture biological (and some of the non-biological) systems. A richer theory that could capture biological reality could also capture physical and chemical phenomena as limiting cases, but
not vice versa
Protein folding and the robustness of cells
The intricate intracellular infrastructure of all known life forms is based on proteins. The folded shape of a protein determines both the protein’s function and the set of molecules it will bind to. This tight coupling between a protein’s function and its interconnections in the molecular interaction network has consequences for the molecular course of evolution. It is also counter to human engineering approaches. Here we report on a simulation study investigating the impact of random errors in an abstract metabolic network of 500 enzymes. Tight coupling between function and interconnectivity of nodes is compared to the case where these two properties are independent. Our results show that the model system under consideration is more robust if function and interconnection are intertwined. These findings are discussed in the context of nanosystems engineering
Irreversible thermodynamics of open chemical networks I: Emergent cycles and broken conservation laws
In this and a companion paper we outline a general framework for the
thermodynamic description of open chemical reaction networks, with special
regard to metabolic networks regulating cellular physiology and biochemical
functions. We first introduce closed networks "in a box", whose thermodynamics
is subjected to strict physical constraints: the mass-action law, elementarity
of processes, and detailed balance. We further digress on the role of solvents
and on the seemingly unacknowledged property of network independence of free
energy landscapes. We then open the system by assuming that the concentrations
of certain substrate species (the chemostats) are fixed, whether because
promptly regulated by the environment via contact with reservoirs, or because
nearly constant in a time window. As a result, the system is driven out of
equilibrium. A rich algebraic and topological structure ensues in the network
of internal species: Emergent irreversible cycles are associated to
nonvanishing affinities, whose symmetries are dictated by the breakage of
conservation laws. These central results are resumed in the relation between the number of fundamental affinities , that of broken
conservation laws and the number of chemostats . We decompose the
steady state entropy production rate in terms of fundamental fluxes and
affinities in the spirit of Schnakenberg's theory of network thermodynamics,
paving the way for the forthcoming treatment of the linear regime, of
efficiency and tight coupling, of free energy transduction and of thermodynamic
constraints for network reconstruction.Comment: 18 page
Field-control, phase-transitions, and life's emergence
Instances of critical-like characteristics in living systems at each
organizational level as well as the spontaneous emergence of computation
(Langton), indicate the relevance of self-organized criticality (SOC). But
extrapolating complex bio-systems to life's origins, brings up a paradox: how
could simple organics--lacking the 'soft matter' response properties of today's
bio-molecules--have dissipated energy from primordial reactions in a controlled
manner for their 'ordering'? Nevertheless, a causal link of life's macroscopic
irreversible dynamics to the microscopic reversible laws of statistical
mechanics is indicated via the 'functional-takeover' of a soft magnetic
scaffold by organics (c.f. Cairns-Smith's 'crystal-scaffold'). A
field-controlled structure offers a mechanism for bootstrapping--bottom-up
assembly with top-down control: its super-paramagnetic components obey
reversible dynamics, but its dissipation of H-field energy for aggregation
breaks time-reversal symmetry. The responsive adjustments of the controlled
(host) mineral system to environmental changes would bring about mutual
coupling between random organic sets supported by it; here the generation of
long-range correlations within organic (guest) networks could include SOC-like
mechanisms. And, such cooperative adjustments enable the selection of the
functional configuration by altering the inorganic network's capacity to assist
a spontaneous process. A non-equilibrium dynamics could now drive the
kinetically-oriented system towards a series of phase-transitions with
appropriate organic replacements 'taking-over' its functions.Comment: 54 pages, pdf fil
The solution space of metabolic networks: producibility, robustness and fluctuations
Flux analysis is a class of constraint-based approaches to the study of
biochemical reaction networks: they are based on determining the reaction flux
configurations compatible with given stoichiometric and thermodynamic
constraints. One of its main areas of application is the study of cellular
metabolic networks. We briefly and selectively review the main approaches to
this problem and then, building on recent work, we provide a characterization
of the productive capabilities of the metabolic network of the bacterium E.coli
in a specified growth medium in terms of the producible biochemical species.
While a robust and physiologically meaningful production profile clearly
emerges (including biomass components, biomass products, waste etc.), the
underlying constraints still allow for significant fluctuations even in key
metabolites like ATP and, as a consequence, apparently lay the ground for very
different growth scenarios.Comment: 10 pages, prepared for the Proceedings of the International Workshop
on Statistical-Mechanical Informatics, March 7-10, 2010, Kyoto, Japa
Complex networks theory for analyzing metabolic networks
One of the main tasks of post-genomic informatics is to systematically
investigate all molecules and their interactions within a living cell so as to
understand how these molecules and the interactions between them relate to the
function of the organism, while networks are appropriate abstract description
of all kinds of interactions. In the past few years, great achievement has been
made in developing theory of complex networks for revealing the organizing
principles that govern the formation and evolution of various complex
biological, technological and social networks. This paper reviews the
accomplishments in constructing genome-based metabolic networks and describes
how the theory of complex networks is applied to analyze metabolic networks.Comment: 13 pages, 2 figure
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