Kinetics of General Enzyme Modifier Mechanism of Botts-Morales

with the model nomenclature of Prof. Baici

Ref.: Antonio Baici, Kinetics of Enzyme-Modifier Interactions, Springer-Verlag, Vienna

All users of EZ-Fit-Ki are advised to download the latest updated version of Software. The latest version includes revisions and 'bug' fixes. Users with an active license can download and activate the software with their current activation code.

EZ-Fit-Ki performs nonlinear regression curve-fitting of data to the Botts-Morales General Modifier enzyme kinetic inhibition mechanisms selected from in internal library of 10 linear and hyperbolic models as defined in Prof. Baici's book (2) .

EZ-Fit-Ki is priced to make it affordable to professionals and students alike. But don't let the low price mislead you. EZ-Fit-Ki is robust and powerful using some of the most sophisticated regression algorithms, including Quadratic Programming, Conjugate Gradient , and Nelder-Mead Simplex methods. Why pay hundreds and yearly license fees when you can have curve-fitting software for a fraction of the cost. Best of all, there are no time limit restrictions or number of uses.

With just a couple of clicks of the mouse, EZ-Fit-Ki simplifies curve fitting your data to enzyme inhibition models. Select one or more equations from an internal library of 10 models, and EZ-Fit-Ki does the rest by fitting the curve to your data set, displaying the statistical results, model parameters, the best fit curve, and the residuals. Plots displayed include Rate vs [S], Residuals of curve-fit, Kmapp vs [I], and MC50 vs [S].

The EZ-Fit-Ki results of your curve-fit includes the fitted parameters, their standard errors , confidence limits, correlation matrix, gradients, and corrected Akaike value. The plots displayed include Rate vs [S], Residuals of curve-fit, Kmapp vs [I], and MC50 vs [S].

Reaction scheme of General Modifier (Botts-Morales) Mechanism

[E]: enzyme, [ES]: enzyme-substrate complex, [ESI]: enzyme-substrate-inhibitor complex, [S]: substrate, [I]: inhibitor, [P]: product of reaction, Km: substrate dissociation constant, Ki: inhibitor binding dissociation constant, and 'a' and 'b' are dimensionless parameters that define the type of the inhibition mechanism.

The library of enzyme inhibition models is based on the rapid-equilibrium assumption and describes the basic mechanisms for the all common reversible inhibition mechanisms. Please note that the quasi-equilibrium assumption for the mechanism under investigation may not always apply. Therefore, the user is advised to check for tight-binding inhibition before using any model equation in this software. At saturating inhibitor concentrations the enzyme activity is either fully or partially inhibited depending on the value of parameter 'b'. The inhibition response can be either linear (b = 0) or partial (0 < b < 1). If b = 1 then both [ES] and [ESI] are equally catalytically active. In contrast, when b = 0 then only the [ES] complex forms product. The factor 'a' represents the difference in binding affinities between the substrate binding to the [EI] complex and the inhibitor binding to the [ES] complex. When a = 1 the binding is equal, but when a = 0, inhibitor only binds to the free enzyme. Differing values of 'a' and 'b' can be used to obtain the common types of inhibition models. Linear and hyperbolic competitive, uncompetitive, noncompetitive, or mixed type inhibition can generally be distinguished by the values of parameters 'a' and 'b'. When more than one model produces similar best curve-fits, it is advised to follow the principle of parsimony and select the mechanism that is the simplest of the competing mechanisms.

Reference:

1- Botts J, Morales M (1953) "Analytical description of the effects of modifiers and of enzyme multivalency upon the steady state catalyzed reaction rate", Trans Faraday Soc 49: 696-707.

2- Antonio Baici (2015) ''Kinetics of Enzyme-Modifier Interactions'', © Springer-Verlag Vienna.

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