title: Enzyme kinetics and metabolic control. A method to test and quantify the effect of enzymic properties on metabolic variables.
abstract: It is usual to study the sensitivity of metabolic variables to small (infinitesimal) changes in the magnitudes of individual parameters such as an enzyme concentration. Here, the effect that a simultaneous change in all the enzyme concentrations by the same factor alpha (Co-ordinate-Control Operation, CCO) has on the variables of time-dependent metabolic systems is investigated. This factor alpha can have any arbitrary large value. First, we assume, for each enzyme measured in isolation, the validity of the steady-state approximation and the proportionality between reaction rate and enzyme concentration. Under these assumptions, any time-invariant variable may behave like a metabolite concentration, i.e. S alpha = Sr (S-type), or like a flux, i.e. J alpha = alpha Jr (J-type). The subscripts r and alpha correspond to the values of the variable before and after the CCO respectively. Similarly, time-dependent variables may behave according to S alpha (t/alpha) = Sr (t) (S-type) or to J alpha (t/alpha) = alpha J r (t) (J-type). A method is given to test these relationships in experimental systems, and to quantify deviations from the predicted behaviour. A positive test for deviations proves the violation of some of the assumptions made. However, the breakdown of the assumptions in an enzyme-catalysed reaction, studied in isolation, may or may not affect significantly the behaviour of the system when the component reaction is embedded in the metabolic network.
authors.affiliation: Department of Genetics, University of Edinburgh, U.K.
authors.forename: L
authors.initials: L
authors.lastname: Acerenza
authors.forename: H
authors.initials: H
authors.lastname: Kacser
mesh_terms: D000704:Analysis of Variance; D004798:Enzymes / Q000378:metabolism*; D007700:Kinetics; D008432:Mathematical Computing; D008722:Methods; D008954:Models, Biological; D013997:Time Factors
chemical_list: D004798:Enzymes