Biology Reference
In-Depth Information
(i.e. certain magnitudes of [S]) and not for others (as is observed, e.g., Ihekwaba
et al., 2004; Nelson et al., 2004), and their nature can depend even qualitatively
on multiple enzymes in the system (e.g. Ihekwaba et al., 2005). Testing whether
the theory indeed explains oscillations that occur in a living cell will first have
to determine what the state of the system is, in a quantitative sense (i.e. how
high S is, and not just whether there is some S or not), then to ask whether for
that state the theory predicts oscillations, and then to test whether under those
conditions oscillations are indeed observed experimentally. The implication is
not only that theory and experiments need to be quantitative but also that they
need to pertain to the conditions of the living state, i.e. they need to be performed
under conditions as close as possible to those that are considered to pertain
in vivo
, preferably in the living organism itself.
An actual example is the following. If one observes synchronous glycolytic
oscillations in intact yeast cells (Davey et al., 1996; Richard et al., 1993),
and one proposes that the stimulation of the enzyme phosphofructokinase by
AMP is 'responsible', one can test this hypothesis by mutating the enzyme
and removing that stimulation. However, any alteration that alters the system
such that its state is no longer in the oscillatory domain, will do away with the
oscillations. In fact the proposed mutation of phosphofructokinase could well do
away with the oscillations by simply shifting the system to a different operating
point even if this product stimulation were responsible for the oscillations. A
proper test of the hypothesis thus removes the AMP effect whilst simultaneously
modulating the system so as to keep it at its operational state. Better, one
removes the AMP effect gradually and asks if the frequency or amplitude of
the oscillations changes (Reijenga et al., 2005b). In nonlinear systems, even
qualitative statements therefore need quantitative tests (Ihekwaba et al., 2005).
How important is this issue? Well, the rate and equilibrium equations for
most biological processes are nonlinear or at least nonproportional (Hill, 1977;
Westerhoff & van Dam, 1987). Moreover, many of the biological processes
that are important for function exhibit properties that one would not see in
individual molecules and that therefore require nonlinear interactions between
those molecules. These processes include differentiation, development, the cell
cycle, robust signal transduction and most transport processes. Their theories
can only be tested if they are quantitative, and strictly only by quantitative
experimentation that is performed inside the living cell.
2.3. Frustrated aspiration of biochemistry and molecular biology
to
biology
Another type of limitation to biochemistry and molecular biology is that they
do not by themselves produce the overlying science, i.e. biology. In principle,
