23.14 Metabolic Regulation
335
Table 23.1 Some examples of metabolic coding
Condition
Symbol
Domain
Glucose deficiency
cAMP
Starvation response
N-deficiency
ppGpp
Stringent response
Redox level
NADH
DNA transcription
StartFraction d bold upper X Over d t EndFraction equals bold upper N bold v commadX
dt = Nv ,
(23.22)
where the “stoicheiometry matrix” bold upper NN specifies how each process depends on the
metabolites. Metabolic control theory (MCT) is concerned with solutions to Eq.
(23.22) and their properties. The dynamical system is generally too complicated for
explicit solutions to be attempted, 43 and numerical solutions are of little use unless
one knows more of the parameters (enzyme rate coefficients) and can measure more of
the variables than are generally available at present. Hence, much current discussion
about metabolism centres on qualitative features. Some are especially noteworthy: It
is well known, from numerous documented examples, that large changes in enzyme
concentration may cause negligible changes in flux through pathways of which they
are a part. Metabolic networks are truly many-component systems, as discussed in
Chap. 12, and, hence, the concept of feedback, so valuable in dealing with systems
of just two components, is of little value in understanding metabolic networks.
Problem. Writebold upper XX andbold vv in Eq. (23.22) as column matrices andbold upper NN as anm times rm × r matrix.
Construct, solve, and discuss an explicit example with only two or three metabolites
and processes.
23.14.2
The Metabolic Code
It is apparent that certain molecules mediating intracellular function (e.g., cAMP)
are ubiquitous in the cell (see Table 23.1). Tomkins (1975) has pointed out that these
molecules are essentially symbols encoding environmental conditions. The domain
of these symbols is defined as the metabolic responses controlled by them. Note that
the symbols are metabolically labile and are not chemically related to molecules
promoting their accumulation. The concept applies to both within and without cells.
Cells affected by a symbol may secrete a hormone, which circulates (e.g., via the
blood) to another cell, where the hormone signal is decoded—often back into the
same symbol.
43 But see Wolkenhauer et al. (2005).