Systems approach to the study of drug transport across membranes using suspension cultures of mammalian cells V. Simultaneous passive transport and biosynthesis

Abstract

A physical model is described for the simultaneous enzymatic bioconversion of a nonelectrolyte solute and the passive transport of both the solute and product of the enzymatic reaction out of cells in culture suspension. The plasma membrane is assumed to be the rate-determining transport barrier. This model provides the basis for the experimental design and analysis of the Michaelis-Menten kinetic parameters of simple enzymatic reactions in situ, the phenomenological transport parameters and other factors. The primary set of differential equations describing the quasisteady state rate of change in the concentration of the solute and product within the cell due to enzyme reaction and transport are given. These are nonlinear and must be solved by numerical methods. However, analytical mathematical expressions have been derived for various cases in the limit when the rate of enzymatic reaction is first or zero order.