A mathematical model representing the extraneuronal O-methylating system of the perfused rat heart

1. A mathematical model was developed to mimic the function of the extraneuronal O-methylating system of the rat heart. Its essential features are: a saturable uptake process (uptake 2), a saturable, intracompartmental enzyme (COMT), the ability of the catecholamine to penetrate the membrane of the model compartment by a diffusional flux obeying first-order kinetics, and the ability of the metabolite to leave the compartment by an efflux obeying first-order kinetics. 2. Of the six kinetic constants of the model compartment five are known from experiments with hearts perfused with 3H-isoprenaline (Kmuptake, Vmaxuptake, Vmaxenzyme, k for amine, k for metabolite); only one constant is unknown (Kmenzyme) for the intact heart cells. 3. Results calculated with the help of the mathematical model were compared with results obtained from rat hearts perfused with 3H-isoprenaline. Although full congruency of results cannot be expected, there was satisfactory agreement between the two sets of results. Apparently, the mathematical model is able to simulate the function of the O-methylating system of the rat heart. 4. Comparison of the two sets of results leads to a definition of the function of the O-methylating system of the perfused rat heart. if all cells of the rat heart participate in the O-methylating system, the Km of the COMT of intact heart cells must be very low (i.e., somewhere between 2 and 5 microM isoprenaline). However, if the O-methylating system comprises only a small fraction of all cells, the COMT of the intact heart cells may well have a correspondingly higher Km.