Biomedical Engineering Reference
In-Depth Information
ways has immense pharmaceutical applications. For example, in a human patho-
genic condition caused by a special metabolic pathway of a pathogenic organ-
ism, the enzyme with the highest control coefficient would be a natural choice
for inhibition.
4.
Some useful definitions
:
Control coefficient
describes the dependency of
flux or metabolite concentration on the property of the enzyme that mediates the
reaction.
Elasticity coefficient
or
elasticity
is a measure of the catalytic property
of an enzyme (in terms of reaction rate) in response to varying concentrations of
the metabolites participating or influencing the reaction.
Pathway flux
is the rate
at which input substances are processed into their subsequent forms.
Me-
tabolomics
is a quantitative estimation of all known and unknown metabolites in
a system under specific physiological conditions.
Metabolite target analysis
describes the correlation between a genetic mutation and its corresponding en-
zyme.
Metabolic profiling
accounts for the role of known metabolites in selected
biochemical pathways.
Metabolic fingerprinting
is the classification of metabo-
lites based on their origin and biological weight.
To build a metabolic model, the concentration of substances, the rate con-
stant and reaction mechanism, as well as the strength of such impacting factors
as pH, temperature, co-factors, and ions are considered. The steady overall state
in the model can be considered as a composite of smaller steady-state conditions
(quasi-steady state) embedded in a larger dynamic system that is open and well
connected to the environment. Application of the steady-state principle helps
uncover unstable states that result in oscillations. For maintenance of the steady
state, the product inhibition loop may be employed in a wide variety of physio-
logical conditions.
Biochemical reactions can be described in two ways, depending on the con-
centration of participating substances. At lower concentrations they are repre-
sented as stochastic events that occur when particles collide at certain
probabilities. A heuristic solution to randomness is provided by mathematically
sound approaches that trace the evolution of an event over a period of time. At
higher concentrations biochemical reactions are represented as deterministic
events best described by ordinary differential equations. If the spatial element
needs to be used during modeling, partial differential equations are employed.
3.8. Software Tools
A mathematically accurate and computationally robust tool is required to
translate life into numbers. Systems Biology Markup Language is a modeling
and simulation language driven by a group of researchers from Caltech (http://
www.sbml.org). The aim is to enable a diverse set of tools to talk to each other
by building cross-platform compatible models. Some of the tools include:
