A simplified approach to derive Cleland model for enzymatic reactions

Abstract

Metabolic modeling can suggest which is the key enzyme activity that needs to be controlled or its activity enhanced for the required production of a metabolite in a pathway. It also helps to find possible drug targets (enzymes to be inhibited). In metabolic modeling, knowing the kinetics of the enzymes involved in a pathway is mandatory. Most enzymatic reactions involve multi-substrates and follow an ordered sequential or ping-pong mechanism. The kinetic parameters involved in the model are obtained by fitting experimental data using a model based on the mechanism. The Cleland model has been used for some years. The grouping of parameters, such as dissociation constant and Michaelis-Menten constant, makes the strategy meaningful and hence the Cleland model is still in use. Although other alternate methods, e. g., the King-Altman method, are available, derivation by determinants can be used to derive a rate expression for the sequential or ping-pong mechanism, they are tedious. Hence, a meaningful modification is suggested in this communication for deriving the enzyme mechanism which is based on Thilakavathi et al. (Biotech Lett 28:1889-1894, 2006) to obtain the Cleland model in an easier way. © 2013 Springer Science+Business Media Dordrecht.