Enzyme kinetics modeling

CASE STUDY ENZYME KINETIC MODELS FOR RESOLUTION OF RACEMIC IBUPROFEN ESTERS IN A MEMBRANE REACTOR... 

This system displays a two-enzyme kinetic model in which bioconversion is controlled by the interaction between the two reactions and the mass transfer. This situation offers a more realistic model for the conditions occurring in vivo, in which some pathways of intermediary metabolism consist of linear sequences of reactions. These pathways take place in highly organized compartments. 

This mechanism is important for compounds that lack sufficient lipid solubility to move rapidly across the membrane by simple diffusion. A membrane-associated protein is usually involved, specificity, competitive inhibition, and the saturation phenomenon and their kinetics are best described by Michaelis-Menton enzyme kinetic models. Membrane penetration by this mechanism is more rapid than simple diffusion and, in the case of active transport, may proceed beyond the point where concentrations are equal on both... 

London, U.K.), and the data are plotted on an Eadie-Hofstee plot (see Fig. 22). It should be noted that, at times, nonlinear regression lines represent the data points on an Eadie-Hofstee plots very poorly because the data reflect the contribution from two kinetically distinct enzymes whereas the computer software attempts to fit all data to an equation appropriate for a single enzyme. A relatively high standard error associated with the estimate of Km suggests that the nonlinear regression did not fit the data very well, and it is possible that a two enzyme model or perhaps an atypical enzyme kinetics model needs to be selected. When Km values are estimated by extrapolating data beyond the concentration range... 

In this chapter I first summarize the theoretical methods developed in my group for enzyme kinetics modeling, which include both electronic and nuclear quantum effects. Then the methods are illustrated through applications to three energy systems, namely, alanine racemase, nitroalkane oxidase and dihydrofolate reductase. 

In this chapter, quantum mechanical methods developed for enzyme kinetics modeling in our group have been presented, including the treatment of the potential energy surface for reactive system and the incorporation of nuclear quantum effects in dynamics simulations. Two aspects are emphasized ... 

The treatment of enzyme kinetics in this book is radically different from the traditional way in which this topic is usually covered. In this book, I have tried to stress the understanding of how models are arrived at, what their Umitations are, and how they can be used in a practical fashion to analyze enzyme kinetic data. With the advent of computers, linear transformations of models have become unnecessary—this book does away with Unear transformations of enzyme kinetic models, stressing the use of nonUnear regression techniques. Linear transformations are not required to carry out analysis of enzyme kinetic data. In this book, I develop new ways of analyzing kinetic data, particularly in the study of pH effects on catalytic activity and multisubstrate enzymes. Since a large proportion of traditional enzyme kinetics used to deal with linearization of data, removing these has both decreased the amount of information that must be acquired and allowed for the development of a deeper understanding of the models used. This, in turn, will increase the efficacy of their use. 

Tmhlar DG, Gao J, Alhambra C, Garcia-Viloca M, Corchado J, Sanchez ML, Villa J (2002) The incorporation of quantum effects in enzyme kinetics modeling. Acc Chem Res 35 341... 

Villa, Acc. Chem. Res., 35, 341 (2002). The Incorporation of Quantum Effects in Enzyme Kinetics Modeling. 

Duggleby, R. G., Morrison, J. F. (1978). Progress curve analysis in enzyme kinetics model discrimination and parameter estimation. Biochim. Biophys. Acta 526, 398 09. 

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