scholarly journals Homo-Oligomerisation in Signal Transduction: Dynamics, Homeostasis, Ultrasensitivity, Bistability

2019 ◽  
Author(s):  
Daniel Koch
Keyword(s):  
Signal Transduction ◽  
Enzyme Regulation ◽  
Monomer Concentration ◽  
Mass Action ◽  
Rate Equations ◽  
Complex Dynamic ◽  
Mass Action Kinetics ◽  
Post Translational Modifications ◽  
Potential Signal ◽  
Reaction Routes

AbstractHomo-oligomerisation of proteins is a ubiquitous phenomenon whose exact role remains unclear in many cases. To identify novel functions, this paper provides an exploration of general dynamical mathematical models of homo-oligomerisation. Simulation and analysis of these models show that homo-oligomerisation on its own allows for a remarkable variety of complex dynamic and steady-state regulatory behaviour such as transient overshoots or homeostatic control of monomer concentration. If post-translational modifications are considered, however, conventional mass-action kinetics leads to thermodynamic inconsistencies due to asymmetric combinatorial expansion of reaction routes. Introducing a conservation principle to balance rate equations re-establishes thermodynamic consistency. Using such balanced models it is shown that oligomerisation can lead to bistability by enabling pseudo-multisite modification and kinetic pseudo-cooperativity via multi-enzyme regulation, thereby constituting a novel motif for bistable modification reactions. Due to these potential signal processing capabilities, homo-oligomerisation could play far more versatile roles in signal transduction than previously appreciated.

Thermodynamics and foundations of mass-action kinetics

2005 ◽  
Vol 30 (1-2) ◽  
pp. 3-113 ◽  
Author(s):  
Miloslav Pekař
Keyword(s):  
Chemical Kinetics ◽  
Reaction Rate ◽  
Chemical Potential ◽  
Kinetic Equations ◽  
Reaction Rates ◽  
Equilibrium States ◽  
Mass Action ◽  
Rate Equations ◽  
Mass Action Kinetics ◽  
Non Equilibrium

A critical overview is given of phenomenological thermodynamic approaches to reaction rate equations of the type based on the law of mass-action. The review covers treatments based on classical equilibrium and irreversible (linear) thermodynamics, extended irreversible, rational and continuum thermodynamics. Special attention is devoted to affinity, the applications of activities in chemical kinetics and the importance of chemical potential. The review shows that chemical kinetics survives as the touchstone of these various thermody-namic theories. The traditional mass-action law is neither demonstrated nor proved and very often is only introduced post hoc into the framework of a particular thermodynamic theory, except for the case of rational thermodynamics. Most published “thermodynamic'’ kinetic equations are too complicated to find application in practical kinetics and have merely theoretical value. Solely rational thermodynamics can provide, in the specific case of a fluid reacting mixture, tractable rate equations which directly propose a possible reaction mechanism consistent with mass conservation and thermodynamics. It further shows that affinity alone cannot determine the reaction rate and should be supplemented by a quantity provisionally called constitutive affinity. Future research should focus on reaction rates in non-isotropic or non-homogeneous mixtures, the applicability of traditional (equilibrium) expressions relating chemical potential to activity in non-equilibrium states, and on using activities and activity coefficients determined under equilibrium in non-equilibrium states.

scholarly journals Non-Equilibrium Thermodynamics View on Kinetics of Autocatalytic Reactions—Two Illustrative Examples

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 585
Author(s):  
Miloslav Pekař
Keyword(s):  
Second Law Of Thermodynamics ◽  
Mass Action ◽  
Rate Equations ◽  
Equilibrium Thermodynamics ◽  
Mass Action Kinetics ◽  
Autocatalytic Reactions ◽  
Chemical Potentials ◽  
Entropic Inequality ◽  
Reaction Stoichiometry ◽  
Non Equilibrium

Autocatalytic reactions are in certain contrast with the linear algebra of reaction stoichiometry, on which rate equations respecting the permanence of atoms are constructed. These mathematical models of chemical reactions are called conservative. Using a non-equilibrium thermodynamics-based theory of chemical kinetics, it is shown how to introduce autocatalytic step into such (conservative) rate equation properly. Further, rate equations based on chemical potentials or affinities are derived, and conditions for the consistency of rate equations with the entropic inequality (the second law of thermodynamics) are illustrated. The theory illustrated here can be viewed as a tool for verifying and generalizing traditional mass-action kinetics by means of modern non-equilibrium thermodynamics, which is able to deal also with such rather problematic cases.

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

scholarly journals Training an asymmetric signal perceptron through reinforcement in an artificial chemistry

2014 ◽  
Vol 11 (93) ◽  
pp. 20131100 ◽  
Author(s):  
Peter Banda ◽  
Christof Teuscher ◽  
Darko Stefanovic
Keyword(s):  
State Of The Art ◽  
Chemical Species ◽  
Mass Action ◽  
Mass Action Kinetics ◽  
Dna Strand Displacement ◽  
Autonomous Adaptation ◽  
Biochemical Systems ◽  
Dna Strand ◽  
Logic Functions ◽  
Application Specific

State-of-the-art biochemical systems for medical applications and chemical computing are application-specific and cannot be reprogrammed or trained once fabricated. The implementation of adaptive biochemical systems that would offer flexibility through programmability and autonomous adaptation faces major challenges because of the large number of required chemical species as well as the timing-sensitive feedback loops required for learning. In this paper, we begin addressing these challenges with a novel chemical perceptron that can solve all 14 linearly separable logic functions. The system performs asymmetric chemical arithmetic, learns through reinforcement and supports both Michaelis–Menten as well as mass-action kinetics. To enable cascading of the chemical perceptrons, we introduce thresholds that amplify the outputs. The simplicity of our model makes an actual wet implementation, in particular by DNA-strand displacement, possible.

scholarly journals How is the effectiveness of immune surveillance impacted by the spatial distribution of spreading infections?

2015 ◽  
Vol 370 (1675) ◽  
pp. 20140289 ◽  
Author(s):  
Ulrich D. Kadolsky ◽  
Andrew J. Yates
Keyword(s):  
Spatial Distribution ◽  
Immune Surveillance ◽  
Critical Density ◽  
Search Time ◽  
Handling Time ◽  
Mass Action ◽  
Mass Action Kinetics ◽  
Expected Time ◽  
Target Ratio ◽  
Infected Cells

What effect does the spatial distribution of infected cells have on the efficiency of their removal by immune cells, such as cytotoxic T lymphocytes (CTL)? If infected cells spread in clusters, CTL may initially be slow to locate them but subsequently kill more rapidly than in diffuse infections. We address this question using stochastic, spatially explicit models of CTL interacting with different patterns of infection. Rather than the effector : target ratio, we show that the relevant quantity is the ratio of a CTL's expected time to locate its next target (search time) to the average time it spends conjugated with a target that it is killing (handling time). For inefficient (slow) CTL, when the search time is always limiting, the critical density of CTL (that required to control 50% of infections, C * ) is independent of the spatial distribution and derives from simple mass-action kinetics. For more efficient CTL such that handling time becomes limiting, mass-action underestimates C * , and the more clustered an infection the greater is C * . If CTL migrate chemotactically towards targets the converse holds— C * falls, and clustered infections are controlled most efficiently. Real infections are likely to spread patchily; this combined with even weak chemotaxis means that sterilizing immunity may be achieved with substantially lower numbers of CTL than standard models predict.

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