Demin O. V.
A.N.Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119899, Vorobjovy Gory, Moscow, Russia,; M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
One of the main aims of modern biological science is to understand regulatory
mechanisms which determine response of any biological system to any perturbation
of external condition. To cope with the task we can apply to the system
either experimental examination or mathematical modeling approach. Each
way has own advantages and disadvantages in dependence on the system under
consideration. The case is that if we consider the system which was intensively
studied before and, consequently, its stoichiometry is well known and kinetics
of partial reactions is quantitatively characterized, then development
of mathematical model of the system allows us to describe (and sometimes
to predict) response of the system to the perturbation of external parameters.
Here, we consider two complex biological systems and show the way in following
which mathematical modeling helps us to understand regulatory properties
of each system. The method of quantification of the regulatory properties
- Metabolic Control Analysis (MCA), was developed in [1-4]. In the framework
of MCA control and elasticity coefficients were determined to describe
system and local (each separate reaction) regulatory properties, respectively.
Applying mathematical modeling and MCA approaches to the following biological
systems:
1) mitochondria respiring on succinate;
2) pathway of signal transduction initiated with epidermal growth factor
(EGF).
We found that
1) to minimize superoxide production and maximize oxygen consumption
in mitochondria there are only two possible ways: to increase concentration
of ATP/ADP translocator or to decrease concentration of succinate ubiquinone
reductase;
2) experimentally observed pronounced maximum in the time course of
tyrosine phosphorylation of EGF receptor and in activation of some its
target protein can be accounted for without any assumptions, requiring
receptor mediated activation of specific tyrosine phosphotase.
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