Biology Reference
In-Depth Information
Using the above equations for kinases and phosphatases in the consecutive steps
in a signalling cascade, Heinrich et al. ( 2002 ) showed that signal amplification is
possible particularly when the level of activation of the pathway ( x i in the above
equation) is small. The signal amplification is demonstrated in Fig. 3.5a for the
signalling cascade shown in Fig. 3.4 . Signal dampening can also be achieved by
such cascades (Fig. 3.5b ). These equations again show, but now in a model-specific
way, that kinases and phosphatases are equally important in determining amplifica-
tion and indeed signal level.
3.9 Examples
3.9.1 Galactose Signalling and Co-response on Galactose
Metabolic Flux in Saccharomyces cerevisiae
Figure 3.6 presents an example where control analysis of signal transduction and
gene expression may lead. Much of this terrain is still unexplored.
3.9.2 Regulatory Strength in Central Nitrogen Metabolism
and Signal Transduction in Escherichia coli
An in silico replica has been constructed for the complete central ammonium
assimilation network of E. coli (Bruggeman et al. 2005 ). Ammonium assimilation
is regulated by a variety of mechanisms, including interactions with metabolites
(substrates, products, effectors), binding and release of regulatory proteins, and
activities of modifier enzymes that covalently modify crucial proteins/enzymes.
This latter part corresponds to signal transduction and a two-component regulatory
system is involved. However, there are more regulatory links in the network, all of
which, even the metabolic links, transduce signal. Using the replica model, the
regulation of the two ammonium assimilating pathways, i.e. glutamine synthetase-
glutamate synthase (GS-GOGAT) and glutamate dehydrogenase (GDH), was dis-
sected quantitatively. Steady states and transient states of the entire network were
examined, but special attention was given to GS, which is by far the most strongly
regulated enzyme in the network. The wild-type and mutants lacking one of the
important regulatory enzymes/proteins (GS, GOGAT, GDH, ATase, and UTase)
were investigated in silico. Overall, the results of the kinetic model indicated that GS
flux was tuned down at 1 mM ammonium, but that the extent of the decrease
depended on the carbon and nitrogen status. Focusing on the transient short-term
effects on GS activity upon a 0.05-1 mM ammonium upshift, the relative, average
contribution of signal flux through the various direct regulators of GS (ADP, ATP,
glutamine, glutamate, adenylylation state) could be calculated in terms of regulatory
strengths. On a second timescale, signal flow through ADP was most regulating,
Search WWH ::




Custom Search