328

2005

Question 7.10

As mentioned in the textbook section, there is a nice article on this by Heinrich et al.

(2002). It describes the properties of phosphatases and kinases, in particular signal ampli­

tude, signal frequency, signal duration (phosphatase must switch off fast enough for both)

and of signal amplitude and signal height (kinase must amplify strongly enough) in signal

cascades. Interestingly, this allows one to develop a mathematical theory that defines the

regulation of the signaling cascade as a function of a finite number of key parameters.

These models can then be used for linear kinase-phosphatase cascades, but also take into

account feedback interactions, crosstalk to other pathways, the cytoskeletal framework

and G proteins.

This mathematical description then shows even more clearly that phosphatases are

more important in their effects on signal rate and duration, whereas signal amplitude is

primarily controlled by kinases. Simple pathway models show good signal amplification

(tasks here directly before) only at the expense of speed.

However, more complicated, realistic pathway models can also achieve high amplifica­

tion and signal rate. For this, a stable, switched-off state of the cascade is important.

Moreover, different agonists can trigger either transient or continuous signals in the same

signaling pathway. The accumulated knowledge of such a model can also be used for the

design of signaling cascades.

Question 7.11

The signal must first be strong enough for this, i.e. the metabolic flux through this meta­

bolic pathway must be high enough. This is regulated by pacemaker enzymes that control

the metabolic flux particularly strongly, i.e. have a particularly high metabolic control

coefficient (see also the contributions by David Fell (2005), metabolic control analysis;

20  Solutions to the Exercises