2,225 research outputs found
The role of backward reactions in a stochastic model of catalytic reaction networks
We investigate the role of backward reactions in a stochastic model of catalytic reaction network, with specific regard to the influence on the emergence of autocatalytic sets (ACSs), which are supposed to be one of the pre-requisites in the transition between non-living to living matter.
In particular, we analyse the impact that a variation in the kinetic rates of forward and backward reactions may have on the overall dynamics.
Significant effects are indeed observed, provided that the intensity of backward reactions is sufficiently high. In spite of an invariant activity of the system in terms of production of new species, as backward reactions are intensified, the emergence of ACSs becomes more likely and an increase in their number, as well as in the proportion of species belonging to them, is observed. Furthermore, ACSs appear to be more robust to fluctuations than in the usual settings with no backward reaction.
This outcome may rely not only on the higher average connectivity of the reaction graph, but also on the distinguishing property of backward reactions of recreating the substrates of the corresponding forward reactions
On RAF Sets and Autocatalytic Cycles in Random Reaction Networks
The emergence of autocatalytic sets of molecules seems to have played an
important role in the origin of life context. Although the possibility to
reproduce this emergence in laboratory has received considerable attention,
this is still far from being achieved. In order to unravel some key properties
enabling the emergence of structures potentially able to sustain their own
existence and growth, in this work we investigate the probability to observe
them in ensembles of random catalytic reaction networks characterized by
different structural properties. From the point of view of network topology, an
autocatalytic set have been defined either in term of strongly connected
components (SCCs) or as reflexively autocatalytic and food-generated sets
(RAFs). We observe that the average level of catalysis differently affects the
probability to observe a SCC or a RAF, highlighting the existence of a region
where the former can be observed, whereas the latter cannot. This parameter
also affects the composition of the RAF, which can be further characterized
into linear structures, autocatalysis or SCCs. Interestingly, we show that the
different network topology (uniform as opposed to power-law catalysis systems)
does not have a significantly divergent impact on SCCs and RAFs appearance,
whereas the proportion between cleavages and condensations seems instead to
play a role. A major factor that limits the probability of RAF appearance and
that may explain some of the difficulties encountered in laboratory seems to be
the presence of molecules which can accumulate without being substrate or
catalyst of any reaction.Comment: pp 113-12
Decomposing Noise in Biochemical Signaling Systems Highlights the Role of Protein Degradation
AbstractStochasticity is an essential aspect of biochemical processes at the cellular level. We now know that living cells take advantage of stochasticity in some cases and counteract stochastic effects in others. Here we propose a method that allows us to calculate contributions of individual reactions to the total variability of a system’s output. We demonstrate that reactions differ significantly in their relative impact on the total noise and we illustrate the importance of protein degradation on the overall variability for a range of molecular processes and signaling systems. With our flexible and generally applicable noise decomposition method, we are able to shed new, to our knowledge, light on the sources and propagation of noise in biochemical reaction networks; in particular, we are able to show how regulated protein degradation can be employed to reduce the noise in biochemical systems
Discreteness-Induced Slow Relaxation in Reversible Catalytic Reaction Networks
Slowing down of the relaxation of the fluctuations around equilibrium is
investigated both by stochastic simulations and by analysis of Master equation
of reversible reaction networks consisting of resources and the corresponding
products that work as catalysts. As the number of molecules is decreased,
the relaxation time to equilibrium is prolonged due to the deficiency of
catalysts, as demonstrated by the amplification compared to that by the
continuum limit. This amplification ratio of the relaxation time is represented
by a scaling function as , and it becomes prominent as
becomes less than a critical value , where is the inverse
temperature and is the energy gap between a product and a resource
Thermodynamically Consistent Coarse Graining of Biocatalysts beyond Michaelis--Menten
Starting from the detailed catalytic mechanism of a biocatalyst we provide a
coarse-graining procedure which, by construction, is thermodynamically
consistent. This procedure provides stoichiometries, reaction fluxes (rate
laws), and reaction forces (Gibbs energies of reaction) for the coarse-grained
level. It can treat active transporters and molecular machines, and thus
extends the applicability of ideas that originated in enzyme kinetics. Our
results lay the foundations for systematic studies of the thermodynamics of
large-scale biochemical reaction networks. Moreover, we identify the conditions
under which a relation between one-way fluxes and forces holds at the
coarse-grained level as it holds at the detailed level. In doing so, we clarify
the speculations and broad claims made in the literature about such a general
flux--force relation. As a further consequence we show that, in contrast to
common belief, the second law of thermodynamics does not require the currents
and the forces of biochemical reaction networks to be always aligned.Comment: 14 pages, 5 figure
A stochastic model of catalytic reaction networks in protocells
Protocells are supposed to have played a key role in the self-organizing
processes leading to the emergence of life. Existing models either (i) describe
protocell architecture and dynamics, given the existence of sets of
collectively self-replicating molecules for granted, or (ii) describe the
emergence of the aforementioned sets from an ensemble of random molecules in a
simple experimental setting (e.g. a closed system or a steady-state flow
reactor) that does not properly describe a protocell. In this paper we present
a model that goes beyond these limitations by describing the dynamics of sets
of replicating molecules within a lipid vesicle. We adopt the simplest possible
protocell architecture, by considering a semi-permeable membrane that selects
the molecular types that are allowed to enter or exit the protocell and by
assuming that the reactions take place in the aqueous phase in the internal
compartment. As a first approximation, we ignore the protocell growth and
division dynamics. The behavior of catalytic reaction networks is then
simulated by means of a stochastic model that accounts for the creation and the
extinction of species and reactions. While this is not yet an exhaustive
protocell model, it already provides clues regarding some processes that are
relevant for understanding the conditions that can enable a population of
protocells to undergo evolution and selection.Comment: 20 pages, 5 figure
Metabolic Futile Cycles and Their Functions: A Systems Analysis of Energy and Control
It has long been hypothesized that futile cycles in cellular metabolism are
involved in the regulation of biochemical pathways. Following the work of
Newsholme and Crabtree, we develop a quantitative theory for this idea based on
open-system thermodynamics and metabolic control analysis. It is shown that the
{\it stoichiometric sensitivity} of an intermediary metabolite concentration
with respect to changes in steady-state flux is governed by the effective
equilibrium constant of the intermediate formation, and the equilibrium can be
regulated by a futile cycle. The direction of the shift in the effective
equilibrium constant depends on the direction of operation of the futile cycle.
High stoichiometric sensitivity corresponds to ultrasensitivity of an
intermediate concentration to net flow through a pathway; low stoichiometric
sensitivity corresponds to super-robustness of concentration with respect to
changes in flux. Both cases potentially play important roles in metabolic
regulation. Futile cycles actively shift the effective equilibrium by expending
energy; the magnitude of changes in effective equilibria and sensitivities is a
function of the amount of energy used by a futile cycle. This proposed
mechanism for control by futile cycles works remarkably similarly to kinetic
proofreading in biosynthesis. The sensitivity of the system is also intimately
related to the rate of concentration fluctuations of intermediate metabolites.
The possibly different roles of the two major mechanisms for cellular
biochemical regulation, namely reversible chemical modifications via futile
cycles and shifting equilibrium by macromolecular binding, are discussed.Comment: 11 pages, 5 figure
BlenX-based compositional modeling of complex reaction mechanisms
Molecular interactions are wired in a fascinating way resulting in complex
behavior of biological systems. Theoretical modeling provides a useful
framework for understanding the dynamics and the function of such networks. The
complexity of the biological networks calls for conceptual tools that manage
the combinatorial explosion of the set of possible interactions. A suitable
conceptual tool to attack complexity is compositionality, already successfully
used in the process algebra field to model computer systems. We rely on the
BlenX programming language, originated by the beta-binders process calculus, to
specify and simulate high-level descriptions of biological circuits. The
Gillespie's stochastic framework of BlenX requires the decomposition of
phenomenological functions into basic elementary reactions. Systematic
unpacking of complex reaction mechanisms into BlenX templates is shown in this
study. The estimation/derivation of missing parameters and the challenges
emerging from compositional model building in stochastic process algebras are
discussed. A biological example on circadian clock is presented as a case study
of BlenX compositionality
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