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MCA |
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With the control coefficients we try to answer the question of "by how
much does each step of a pathway control a system variable?". However
it is also very important to quantify the effects of substances foreign
to the pathway on its variables.
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Internal and External Effectors |
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The enzymes of a metabolic system can be affected by two types of
biochemical substances: those that are produced in the system itself (the
internal effectors), and those that are added to the system from an
external source (external effectors). Substances of the latter type can
be, for example, drugs added to the system or hormones produced by other cells
of the same organism. The internal effectors are variables of the system and,
therefore, are not primary causes, but rather effects. Their role in the
control of the system is that of being the "conveyor belts" of the machinery,
which is taken into account by the connectivity relations, described in the
previous section. On the other hand, the external
effectors are causes, rather than effects (as they are under control of agents
external to the system), therefore it is useful to quantify their effect on the
system.
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The Partitioned Response Coefficients |
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The primary effect of an external effector on a metabolic pathway is to
affect (enhance or reduce) the rate of some of the enzymes. Such an effect is
quantified by the enzyme elasticity coefficients. But
as these rates change, so will the system variables of the pathway: the
flux(es) and internal metabolite concentrations. How the latter change with
changes in rates of the enzymes is quantified by the flux- and concentration- control coefficients. Thus the effect of the external
effector (X) on a pathway variable (A) is:
 (9)
where the effector X affects the enzyme k only. More
generally external metabolites affect more than one enzyme of the pathway,
and so the change in the system variable is the sum of the effects through
all the enzymes whith which the effector interacts. This is know as the
partinioned response coefficient
(Kacser & Burns 1973)
and is given by:
 (10)
where the summation is over all affected enzymes.
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Group |
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