  Classical descriptions of enzyme kinetics ignore the physical nature of the
intracellular environment. Main implicit assumptions behind such approaches are
that reactions occur in compartment volumes which are large enough so that
molecular discreteness can be ignored and that molecular transport occurs via
diffusion. Starting from a master equation description of enzyme reaction
kinetics and assuming metabolic steady-state conditions, we derive novel
mesoscopic rate equations which take into account (i) the intrinsic molecular
noise due to the low copy number of molecules in intracellular compartments
(ii) the physical nature of the substrate transport process, i.e. diffusion or
vesicle-mediated transport. These equations replace the conventional
macroscopic and deterministic equations in the context of intracellular
kinetics. The latter are recovered in the limit of infinite compartment
volumes. We find that deviations from the predictions of classical kinetics are
pronounced (hundreds of percent in the estimate for the reaction velocity) for
enzyme reactions occurring in compartments which are smaller than approximately
200nm, for the case of substrate transport to the compartment being mediated
principally by vesicle or granule transport and in the presence of competitive
enzyme inhibitors. This has implications for the common approach of modelling
large intracellular reaction networks using ordinary differential equations and
also for the calculation of the effective dosage of competitive inhibitor
drugs.
