Modern theories of metabolic control and their applications

  title={Modern theories of metabolic control and their applications},
  author={Hans V. Westerhoff and Albert K. Groen and Ronald J. A. Wanders},
  journal={Bioscience Reports},
Existing, qualitative notions with respect to the way in which enzyme properties control metabolism are discussed in the light of the control analysis developed by H. Kacser and J. A. Burns ((1973) in: Rate Control of Biological Processes, Davies DD, ed., Cambridge University Press, pp. 63–104) and R. Heinrich and T. A. Rapoport ((1974) Eur. 3. Biochem.42, 89–95), and recent experimental data. Points at which the existing notions should be adjusted are: (i) Metabolic control is shared by… 
Thermodynamics of the control of metabolism
Application of this extended control analysis of metabolic systems in terms of Gibbs free energies and free-energy elasticity coefficients to some biochemical reactions, including proton translocation, demonstrates that problems arising in the control analysis because of conservation can be circumvented.
Metabolic control and its analysis
Algebraic solutions have been used to determine the factors responsible for the degree of amplification of flux control coefficients by substrate cycles and to show that it is possible to derive expressions for the elasticities of a group of enzymes.
Modern Control Theories: a Consumers’ Test
Control analysis has been applied to some extent by workers outside the group of the originators of the theories, and it is suggested that control analysis is easier to understand for the mathematically untrained.
Signalling control strength.
Prospects for advancing the understanding of complex biochemical systems
The application of mathematical theories to understanding the behaviour of complex biochemical systems is reviewed. Key aspects of behaviour are identified as the flux through particular pathways in
Matrix method for determining steps most rate-limiting to metabolic fluxes in biotechnological processes. 1987.
The metabolic control theory developed by Kacser, Burns, Heinrich, and Rapoport is briefly outlined, extended, and transformed so as optimally to address some biotechnological questions. The
Control of Oxidative Phosphorylation in Yeast Mitochondria: The Role of Phosphate Carrier and pH
The problem of the control of oxidative phosphorylations has been the object of a great deal of discussion over the last few years and it has been shown that the control exerted by the adenine nucleotide translocator depends not only on the respiration rate, but also on the complexity of the metabolic network and on the model of ATP utilization.


Control of mitochondrial respiration
Quantification of the contribution of various steps to the control of mitochondrial respiration.
Inference titration studies were carried out in order to quantify the amount of control (control strength) exerted by different steps in oxidative phosphorylation on the rate of mitochondrial oxygen uptake.
Metabolic regulation and mathematical models.
Control of the flux in the arginine pathway of Neurospora crassa. Modulations of enzyme activity and concentration.
It is shown that control of the flux is shared among all the enzymes of the pathway, and the concept of a 'rate-limiting step' is found to be inadequate and is replaced by a quantitative measure, the Sensitivity Coefficient, which takes account of all the interactions.