2016-Metabolic control analysis.pdfVIP

Eur. J. Biochem. 191,413-420 1990 0FEBS 1990 Metabolic control analysis Sensitivity of control coefficients to elasticities J. Rankin SMALL and David A. FELL School of Biological and Molecular Sciences, Oxford Polytechnic, Oxford, England Received December 22, 1989 - EJB 89 1522 This paper illustrates a method to calculate the sensitivities of control coefficients to the elasticities which determine their values and it is shown that these sensitivities are systemic properties. We show, both theoretically and with a practical example, how they can be used to investigate: a the relative importance of a particular elasticity in the determination of the value of a control coefficient; b the effect of experimental error on the values of the control coefficients and c the construction of confidence limits around the values of the control coefficients. Many biochemists now believe that the study of metabolic reaction, I represents any external effectors and s.s. signifies control should be such that quantitative, as opposed to quali- that this elasticity is defined at the steady-state values of all tative, interpretations can be made. To facilitate such studies, other variables. a theory, now known as metabolic control analysis, was de- A number of relationships that link the values of the con- veloped by Kacser and Burns [I] and Heinrich and Rapoport trol coefficients to the values of the elasticities have been [2j for a recent review see [3j . The theory, including sub- derived [l, 2, 5-81; these relationships allow the determi- sequent extensions [4 -81, involves the definition of two types nation of the control coefficients in terms of the individual of coefficients. elasticities of the system. A simple matrix algorithm to obtain a The control coefficients. These coefficients are proper- the flux control coefficients in such a way was demonstrated ties of the intact metabolic