in Wiley InterScience (www.interscience.wiley.com).We develop a new dimensionless representation of the time-dependent mass balances for the Michaelis-Menten (MM) reaction mechanism; we identify several dimensionless parameters that control the fundamental nature of the solution; and we solve the scaled equations with a combined regular and singular perturbation expansion. Unlike several approximate solutions to the MM problem offered previously in the literature, each of which is valid only for some limited range of conditions, the new solution converges accurately for any combination of initial substrate concentration, initial enzyme concentration, and kinetic rate constants. We discuss the physical significance and interdependence of the dimensionless parameters that emerge from our scaling analysis; we use these parameters to categorize previous approximations for the MM problem and to delimit their accuracy; and we verify the accuracy of our solution via comparisons to an exact numerical solution and various approximations offered previously by others. 2008 American Institute of Chemical Engineers AIChE J, 54: [1344][1345][1346][1347][1348][1349][1350][1351][1352][1353][1354][1355][1356][1357] 2008 Keywords: mathematical modeling, reaction kinetics, bioengineering Introduction Homogeneous, enzyme-catalyzed reactions nearly always occur via a two-step process known as the ''MichaelisMenten'' (MM) mechanism. [1][2][3] In the first elementary reaction, the enzyme E attaches reversibly to the substrate molecule S to form a complex C, i.e.and in the second elementary reaction, the bound enzyme converts the substrate irreversibly to product P and releases it, which returns the enzyme to solution, i.e.,The parameters k 1 [units mol/vol-time], k 21 [time
21], and k 2 [time 21 ] are the kinetic rate constants for each elementary reaction as shown. 4 One frequently seeks to measure these rate constants (or combinations thereof) as accurately as possible for various enzyme/substrate combinations to compare their performance or for use in simulations of complex, multi-step, multi-component biochemical processes. 5,6 Four ordinary differential equations are required to describe the time-dependent concentrations E(t), S(t), C(t), and P(t) in a reactor where an MM reaction is occurring:From this point forward we use combined kinetics parameters that are preferred by the biochemistry community:Correspondence concerning this article should be addressed to A. B. Anton at aba6@cornell.edu. ; K D ¼ k À1 =k 1 is the dissociation equilibrium constant of the enzyme-substrate complex; andÞ=k 1 is the MM constant. 4 Each of these has units of concentration [mol/vol] and can range between zero and infinity for different enzymesubstrate combinations. They quantify in some sense the relative tendency of enzyme and substrate to distribute among initial, intermediate, and final states during the reaction. Typically, the reaction is carried out in a closed batch reactor charged with an initial concentration of enzyme (E T ) and subs...