Use and abuse of the quasi-steady-state approximation

The transient kinetic behaviour of an open single enzyme, single substrate reaction is examined. The reaction follows the Van Slyke–Cullen mechanism, a spacial case of the Michaelis–Menten reaction. The analysis is performed both with and without applying the quasi-steady-state approximation. The analysis of the full system shows conditions for biochemical pathway coupling, which yield sustained oscillatory behaviour in the enzyme reaction. The reduced model does not demonstrate this behaviour. The results have important implications in the analysis of open biochemical reactions and the modelling of metabolic systems

Enzyme kinetics far from the standard quasi-steady-state and equilibrium approximations

Analytic approximations of the time-evolution of the single enzyme-substrate reaction are valid for all but a small region of parameter space in the positive initial enzyme-initial substrate concentration plane. We find velocity equations for the substrate decomposition and product formation with the aid of the total quasi-steady-state approximation and an aggregation technique for cases where neither the more normally employed standard nor reverse quasi-steady-state approximations are valid. Applications to determining reaction kinetic parameters are discussed

A century of enzyme kinetics. Should we believe in the Km and vmax estimates?

The application of the quasi-steady-state approximation (QSSA) in biochemical kinetics allows the reduction of a complex biochemical system with an initial fast transient into a simpler system. The simplified system yields insights into the behavior of the biochemical reaction, and analytical approximations can be obtained to determine its kinetic parameters. However, this process can lead to inaccuracies due to the inappropriate application of the QSSA. Here we present a number of approximate solutions and determine in which regions of the initial enzyme and substrate concentration parameter space they are valid. In particular, this illustrates that experimentalists must be careful to use the correct approximation appropriate to the initial conditions within the parameter space

Bulletin of Mathematical Biology - facts, figures and comparisons

The Society for Mathematical Biology (SMB) owns the Bulletin of Mathematical Biology (BMB). This is an international journal devoted to the interface of mathematics and biology. At the 2003 SMB annual meeting in Dundee the Society asked the editor of the BMB to produce an analysis of impact factor, subject matter of papers, submission rates etc. Other members of the society were interested in the handling times of articles and wanted comparisons with other (appropriate) journals. In this article we present a brief history of the journal and report on how the journal impact factor has grown substantially in the last few years. We also present an analysis of subject areas of published papers over the past two years. We finally present data on times from receipt of paper to acceptance, acceptance to print (and to online publication) and compare these data with some other journals

Limit cycles in the presence of convection, a first order analysis

We consider a diffusion model with limit cycle reaction functions. In an unbounded domain, diffusion spreads pattern outwards from the source. Convection adds instability to the reaction-diffusion system. We see the result of the instability in a readiness to create pattern. In the case of strong convection, we consider that the first-order approximation may be valid for some aspects of the solution behaviour. We employ the method of Riemann invariants and rescaling to transform the reduced system into one invariant under parameter change. We carry out numerical experiments to test our analysis. We find that most aspects of the solution do not comply with this, but we find one significant characteristic which is approximately first order. We consider the correspondence of the Partial Differential Equation with the Ordinary Differential Equation along rays from the initiation point in the transformed system. This yields an understanding of the behaviour

Turing pattern outside of the Turing domain

There are two simple solutions to reaction-diffusion systems with limit-cycle reaction kinetics, producing oscillatory behaviour. The reaction parameter $\mu$ gives rise to a ‘space-invariant’ solution, and $\mu$ versus the ratio of the diffusion coefficients gives rise to a ‘time-invariant’ solution. We consider the case where both solution types may be possible. This leads to a refinement of the Turing model of pattern formation. We add convection to the system and investigate its effect. More complex solutions arise that appear to combine the two simple solutions. The convective system sheds light on the underlying behaviour of the diffusive system

Multiscale modeling in biology

The 1966 science-fction film Fantastic Voyage captured the public imagination with a clever idea: what fantastic things might we see and do if we could minaturize ourselves and travel through the bloodstream as corpuscles do? (This being Hollywood, the answer was that we'd save a fellow scientist from evildoers.

A mathematical investigation of a clock and wavefront model for somitogenesis

Abstract Somites are transient blocks of cells that form sequentially along the antero-posterior axis of vertebrate embryos. They give rise to the vertebrae, ribs and other associated features of the trunk. In this work we develop and analyse a mathematical formulation of a version of the Clock and Wavefront model for somite formation, where the clock controls when the boundaries of the somites form and the wavefront determines where they form. Our analysis indicates that this interaction between a segmentation clock and a wavefront can explain the periodic pattern of somites observed in normal embryos. We can also show that a simplification of the model provides a mechanism for predicting the anomalies resulting from perturbation of the wavefront

Formation of vertebral precursors: Past models and future predictions

Disruption of normal vertebral development results from abnormal formation and segmentation of the vertebral precursors, called somites. Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. We review the most popular models of somite formation: Cooke and Zeeman's clock and wavefront model, Meinhardt's reaction-diffusion model and the cell cycle model of Stern and co-workers, and discuss the consistency of each in the light of recent experimental findings concerning FGF-8 signalling in the presomitic mesoderm (PSM). We present an extension of the cell cycle model to take account of this new experimental evidence, which shows the existence of a determination front whose position in the PSM is controlled by FGF-8 signalling, and which controls the ability of cells to become competent to segment. We conclude that it is, at this stage, perhaps erroneous to favour one of these models over the others