Responses of Metabolic Systems to Large Changes in Enzyme Activities

Abstract

It is now possible in many organisms to use molecular biological tools to overexpress a gene coding for an enzyme. This overexpression can result in very large changes in enzyme activity. The effects of this overexpression on the metabolic system in which this enzyme acts are difficult to predict. Metabolic Control Analysis¹ may give us some indication of the likely effect (small or large), via the control coefficient of that enzyme to a particular flux or metabolite, but due to the infinitesimal nature of these coefficients, i.e.,

$$ C_{E_i^o}^{{J^o}} = {\left( {{{\partial J} \over {\partial {E_i}}}} \right)^o}.{{E_i^o} \over {{J^o}}}, $$

(1)

where ${\left( {{{\partial J} \over {\partial {E_i}}}} \right)^o}$ is the slope of the J versus E relationship at (J ^o, E _i ^o), extrapolation to large changes is unlikely to be quantitatively accurate.