The kinetics of facilitated diffusion followed by enzymatic conversion of the substrate

The uptake of a substrate that is transported into the cell by facilitated diffusion and subsequently converted in a series of enzymatic reactions, measured as a function of the external concentration, does not usually show the rectangular hyperbolic function characteristic of Michaelis-Menten kinetics. Instead, a seemingly biphasic curve is observed, consisting of Michaelis-Menten kinetics at low concentrations and no further uptake at higher levels. By combining the equations for facilitated diffusion and an enzymatic reaction, we have derived an equation that describes the overall rate of uptake and metabolism of a substrate that is transported across the plasma membrane by facilitated diffusion. Modelling based on this equation simulated the kinetics found experimentally, as long as the kinetic parameters of the carrier were chosen to render it asymmetric. The overall rate was influenced by the kinetics of both reactions over a wide range of concentrations, confirming the principles of the 'Control Analysis' theory in an independent manner.