12 research outputs found
Singularly Perturbed Monotone Systems and an Application to Double Phosphorylation Cycles
The theory of monotone dynamical systems has been found very useful in the
modeling of some gene, protein, and signaling networks. In monotone systems,
every net feedback loop is positive. On the other hand, negative feedback loops
are important features of many systems, since they are required for adaptation
and precision. This paper shows that, provided that these negative loops act at
a comparatively fast time scale, the main dynamical property of (strongly)
monotone systems, convergence to steady states, is still valid. An application
is worked out to a double-phosphorylation ``futile cycle'' motif which plays a
central role in eukaryotic cell signaling.Comment: 21 pages, 3 figures, corrected typos, references remove
Supplementary Material for: Green Inclusions in Neutrophils and Monocytes Are an Indicator of Acute Liver Injury and High Mortality
<p>No Abstract</p><p><br></p
Quasi steady-state approximations in complex intracellular signal transduction networks - a word of caution
Enzyme reactions play a pivotal role in intracellular signal transduction. Many enzymes are known to possess Michaelis\u2013Menten (MM) kinetics and the MM approximation is often used when modeling enzyme reactions. However, it is known that the MM approximation is only valid at low enzyme concentrations, a condition not fulfilled in many in vivo situations. Recently the total quasi steady-state approximation (tQSSA) has been developed for enzymes with MM kinetics. This new approximation is valid not only whenever the MM approximation is, but moreover in a greatly extended parameter range. Starting from a single reaction and arriving at the mitogen activated protein kinase (MAPK) cascade, we give several examples of biologically realistic scenarios where the MM approximation leads to quantitatively as well as qualitatively wrong conclusions, and show that the tQSSA improves the accuracy of the simulations greatly