ESTIMATION OF STEADY-STATE FLUX RATES IN METABOLIC SYSTEMS BY COMPUTER-SIMULATIONS OF RADIOACTIVE-TRACER EXPERIMENTS

The dynamics of radioactive tracers in metabolic systems can be mathem atically modelled by coupled systems of differential equations for bot h the concentrations and the specific radioactivitie of the metabolite s involved. Computer simulations, i. e. direct fitting of numerical so lutions of these equations to observed time-courses of metabolites and specific radioactivities, enables one to estimate unknown kinetic par ameters of the system. The theoretical fundamentals of this approach a nd the main steps towards the quantitative assessment of flux rates in stationary metabolic systems are outlined. An application of the meth od to the purine nucleotide metabolism of Ehrlich ascites tumor cells is given based on a simplified model of this pathway. The obtained ste ady-state flux rates indicate a marked increase in the metabolism of t he adenine nucleotides during the proliferating phase in comparison to the resting phase of tumor growth.