A study of the temperature dependence of bienzyme systems and enzymatic chains

It is known that most enzyme-facilitated reactions are highly temperature dependent processes. In general, the temperature coefficient, Q10, of a simple reaction reaches 2.0-3.0. Nevertheless, some enzyme-controlled processes have much lower Q10 (about 1.0), which implies that the process is almost temperature independent, even if individual reactions involved in the process are themselves highly temperature dependent. In this work, we investigate a possible mechanism for this apparent temperature compensation: simple mathematical models are used to study how varying types of enzyme reactions are affected by temperature. We show that some bienzyme-controlled processes may be almost temperature independent if the modules involved in the reaction have similar temperature dependencies, even if individually, these modules are strongly temperature dependent. Further, we show that in non-reversible enzyme chains the stationary concentrations of metabolites are dependent only on the relationship between the temperature dependencies of the first and last modules, whilst in reversible reactions, there is a dependence on every module. Our findings suggest a mechanism by which the metabolic processes taking place within living organisms may be regulated, despite strong variation in temperature

A study of the temperature dependence of bienzyme systems and enzymatic chains

It is known that most enzyme-facilitated reactions are highly temperature dependent processes. In general, the temperature coefficient, Q 10 , of a simple reaction reaches 2.0 -3.0. Nevertheless, some enzyme-controlled processes have much lower Q 10 (about 1.0), which implies that the process is almost temperature independent, even if individual reactions involved in the process are themselves highly temperature dependent. In this work, we investigate a possible mechanism for this apparent temperature compensation: simple mathematical models are used to study how varying types of enzyme reactions are affected by temperature. We show that some bienzyme-controlled processes may be almost temperature independent if the modules involved in the reaction have similar temperature dependencies, even if individually, these modules are strongly temperature dependent. Further, we show that in non-reversible enzyme chains the stationary concentrations of metabolites are dependent only on the relationship between the temperature dependencies of the first and last modules, whilst in reversible reactions, there is a dependence on every module. Our findings suggest a mechanism by which the metabolic processes taking place within living organisms may be regulated, despite strong variation in temperature

Computational modelling elucidates the mechanism of ciliary regulation in health and disease

<p>Abstract</p> <p>Background</p> <p>Ciliary dysfunction leads to a number of human pathologies, including primary ciliary dyskinesia, nephronophthisis, situs inversus pathology or infertility. The mechanism of cilia beating regulation is complex and despite extensive experimental characterization remains poorly understood. We develop a detailed systems model for calcium, membrane potential and cyclic nucleotide-dependent ciliary motility regulation.</p> <p>Results</p> <p>The model describes the intimate relationship between calcium and potassium ionic concentrations inside and outside of cilia with membrane voltage and, for the first time, describes a novel type of ciliary excitability which plays the major role in ciliary movement regulation. Our model describes a mechanism that allows ciliary excitation to be robust over a wide physiological range of extracellular ionic concentrations. The model predicts the existence of several dynamic modes of ciliary regulation, such as the generation of intraciliary Ca²⁺spike with amplitude proportional to the degree of membrane depolarization, the ability to maintain stable oscillations, monostable multivibrator regimes, all of which are initiated by variability in ionic concentrations that translate into altered membrane voltage.</p> <p>Conclusions</p> <p>Computational investigation of the model offers several new insights into the underlying molecular mechanisms of ciliary pathologies. According to our analysis, the reported dynamic regulatory modes can be a physiological reaction to alterations in the extracellular environment. However, modification of the dynamic modes, as a result of genetic mutations or environmental conditions, can cause a life threatening pathology.</p

A Systems Model for Immune Cell Interactions Unravels the Mechanism of Inflammation in Human Skin

Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes

Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels

Cyclic adenosine monophosphate and cyclic guanosine monophosphate are universal intracellular messengers whose concentrations are regulated by molecular networks comprised of different isoforms of the synthases adenylate cyclase or guanylate cyclase and the phosphodiesterases which degrade these compounds. In this paper, we employ a systems biology approach to develop mathematical models of these networks that, for the first time, take into account the different biochemical properties of the isoforms involved. To investigate the mechanisms underlying the joint regulation of cAMP and cGMP, we apply our models to analyse the regulation of cilia beat frequency in Paramecium by Ca(2+). Based on our analysis of these models, we propose that the diversity of isoform combinations that occurs in living cells provides an explanation for the huge variety of intracellular processes that are dependent on these networks. The inclusion of both G-protein receptor and Ca(2+)-dependent regulation of AC in our models allows us to propose a new explanation for the switching properties of G-protein subunits involved in nucleotide regulation. Analysis of the models suggests that, depending on whether the G-protein subunit is bound to AC, Ca(2+) can either activate or inhibit AC in a concentration-dependent manner. The resulting analysis provides an explanation for previous experimental results that showed that alterations in Ca(2+) concentrations can either increase or decrease cilia beat frequency over particular Ca(2+) concentration ranges