Feedback: Fundamental relationship or frame or mind?

Riggs, Douglas S.

doi:10.1016/0065-2571(67)90026-x

Cited by 5 publications

(3 citation statements)

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“…If the rate of the unidirectional demand rcaction catalysed by E4 is a hyperbolic function of S,, then e: will vary between 0 (saturated) and I (unsaturated). This follows from the equation (33) where K,, is the Michaelis constant of the demand reaction for S3. We can now ask how insensitive the demand block must be to changes in S3, i.e.…”

Section: Internal Regulation In a Model Metabolic Systemmentioning

confidence: 99%

“…This follows from the equation (33) where K,, is the Michaelis constant of the demand reaction for S3. We can now ask how insensitive the demand block must be to changes in S3, i.e.…”

Section: Internal Regulation In a Model Metabolic Systemmentioning

confidence: 99%

“…However, our current perception of the design of metabolic systems is that this response in the steady-state fluxes and concentrations to a change in an external regulator is itself internally regulated by being coordinated around key metabolite(s) internal to the system. These metabolites, which we shall call internal regulators, stand in a feedback relationship [33] with the enzyme rates of the system, i.e. a circular causal relationship in which the steady-state concentrations of these key metabolites and the enzyme rates are interdependent.…”

Section: Definitionsmentioning

confidence: 99%

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Quantitative assessment of regulation in metabolic systems

Hofmeyr

Cornish‐Bowden²

1991

European Journal of Biochemistry

130

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We show how metabolic regulation as commonly understood in biochemistry can be described in terms of metabolic control analysis. The steady-state values of the variables of metabolic systems (fluxes and concentrations) are determined by a set of parameters. Some of these parameters are concentrations that are set by the environment of the system; they can act as external regulators by communicating changes in the environment to the metabolic system. How effectively a system is regulated depends both on the degree to which the activity of the regulatory enzyme with which a regulator interacts directly can be altered by the regulator (its regulability) and on the ability of the regulatory enzyme to transmit the changes to the rest of the system (its regulatory capacity). The regulatory response of a system also depends on its internal organisation around key variable metabolites that act as internal regulators. The regulatory performance of the system can be judged in terms of how sensitively the fluxes respond to the external stimulus and to what degree homeostasis in the concentrations of the internal regulators is maintained. We show how, on the level of both external and internal regulation, regulability can be quantified in terms of an elasticity coefficient and regulatory capacity in terms of a control coefficient. Metabolic regulation can therefore be described in terms of metabolic control analysis. The combined response relationship of control analysis relates regulability and regulatory capacity and allows quantification of the regulatory importance of the various interactions of regulators with enzymes in the system. On this basis we propose a quantitative terminology and analysis of metabolic regulation that shows what we should measure experimentally and how we should interpret the results. Analysis and numerical simulation of a simple model system serves to demonstrate our treatment.Since the discovery of the phenomenon of end-product inhibition in cellular metabolism 11, 21 and the formulation of the first definite ideas on metabolic regulation [3], a vast amount of research has yielded many intricate ways in which enzyme activity and concentration can be changed : cooperative and allosteric effects 14-61, covalent modification cascades [7], genetic mechanisms of induction and repression [S], to mention a few. The terms 'regulation' and 'control' have been applied indiscriminately to all of these phenomena, even to man-made manipulations, so much so that they have almost become devoid of any specific, and therefore useful, meaning. Being terms that are also used, often uncritically, in everyday life, they are admittedly difficult to define qualitatively, and even more so quantitatively, in a specific context such as metabolism, although notable exceptions exist [9 -111. Quantitative definition of control and regulation implies the use of a suitable mathematical framework. Such a framework, called metabolic control analysis, has been under development during the last two decades [12, 131. In this p...

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Section: Internal Regulation In a Model Metabolic Systemmentioning

confidence: 99%

“…This follows from the equation (33) where K,, is the Michaelis constant of the demand reaction for S3. We can now ask how insensitive the demand block must be to changes in S3, i.e.…”

Section: Internal Regulation In a Model Metabolic Systemmentioning

confidence: 99%

Section: Definitionsmentioning

confidence: 99%

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