The Mutual Co-Action of two Regulatory Mechanisms
Realizing Optimal Autoregulation of Metabolism
G. DETcHEv, and A. MOSKONA t
With 1 Figure
Abstract
Autoregulation of metabolism is considered by applying certain elements of
an extended thermodynamics of regulated irreversible processes. Since the application of the existing thermodynamics of irreversible processes is invalid for
several reasons~· chemical reactions are running far from their equilibrium;
ONSAGER'S relations do not hold true because of the existence of feedbacks;
minimum entropy production does not occur-a system of equations has been
derived based upon BELUIAN'S dynamic programming and PONTRIJAGIN'S
maximum principle, which overcomes these difficulties.
The existing experimental data concerning control of cell metabolism
unambiguously suggest the existence of two regulatory mechanisms-the
one acting swiftly and based on an allosteric modification of the enzyme
pool activity, and the other going into action more slowly and based on
control of the svnthesis of the respective enzymes.
The investigation of the first regulatory mechanism dates back to the
discovery by !\:OVIC K and SZILARD [5], that tryptophan inhibits the synthesis
of its own precursor. It is of special interest to us that usually the activity
of the first enzyme in a given chain is inhibited in this way, either by the
end-product [6] or b\' some more or less distant precursors or even intermediates; inhibition is exerted also by end-products of simultaneously
proceeding side pathways, the so called cross inhibition [4].
The second regulaton' mechanism is most thoroughly studied in the
p-galactosidase system of E. coli. By means of tracer methods it is now
proved that the increase in enzyme activity is actually due to a de-novo
synthesis of the enzyme. The question is raised about how the two regulatory mechanisms are correlated. The experiments of GORINI [3], who had
found the effect of arginine on E. coli, show that the allosteric inhibition
is much more sensitive to changes in arginine concentration than is repression. For this reason DAVIS [1 J terms the first regulation "fine" and the
second one "rough" adjustment (or tuning in).
13*
Realizing Optimal Autoregulation of Metabolism
G. DETcHEv, and A. MOSKONA t
With 1 Figure
Abstract
Autoregulation of metabolism is considered by applying certain elements of
an extended thermodynamics of regulated irreversible processes. Since the application of the existing thermodynamics of irreversible processes is invalid for
several reasons~· chemical reactions are running far from their equilibrium;
ONSAGER'S relations do not hold true because of the existence of feedbacks;
minimum entropy production does not occur-a system of equations has been
derived based upon BELUIAN'S dynamic programming and PONTRIJAGIN'S
maximum principle, which overcomes these difficulties.
The existing experimental data concerning control of cell metabolism
unambiguously suggest the existence of two regulatory mechanisms-the
one acting swiftly and based on an allosteric modification of the enzyme
pool activity, and the other going into action more slowly and based on
control of the svnthesis of the respective enzymes.
The investigation of the first regulatory mechanism dates back to the
discovery by !\:OVIC K and SZILARD [5], that tryptophan inhibits the synthesis
of its own precursor. It is of special interest to us that usually the activity
of the first enzyme in a given chain is inhibited in this way, either by the
end-product [6] or b\' some more or less distant precursors or even intermediates; inhibition is exerted also by end-products of simultaneously
proceeding side pathways, the so called cross inhibition [4].
The second regulaton' mechanism is most thoroughly studied in the
p-galactosidase system of E. coli. By means of tracer methods it is now
proved that the increase in enzyme activity is actually due to a de-novo
synthesis of the enzyme. The question is raised about how the two regulatory mechanisms are correlated. The experiments of GORINI [3], who had
found the effect of arginine on E. coli, show that the allosteric inhibition
is much more sensitive to changes in arginine concentration than is repression. For this reason DAVIS [1 J terms the first regulation "fine" and the
second one "rough" adjustment (or tuning in).
13*