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Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation by JÜRGEN SCHMIDER; DAVID J. GREENBLATT; JEROLD S. HARMATZ; RICHARD I. SHADER is a Medicine article available to read on EtoBox.

What is Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation about?

1To determine kinetic parameters (__V__~max~, __K__~__m__~) for cytochrome P450 (CYP) mediated metabolic pathways, nonlinear least squares regression is commonly used to fit a model equation (e.g., Michaelis Menten [MM]) to sets of data points (reaction velocity vs substrate concentration). This method can also be utilized to determine the parameters for more complex mechanisms involving allosteric or multi‐enzyme systems. Akaike's Information Criterion (AIC), or an estimation of improvement of fit as successive parameters are introduced in the model (F‐test), can be used to determine whether application of more complex models is helpful. To evaluate these approaches, we have examined the complex enzyme kinetics of amitriptyline (AMI) N‐demethylation __in vitro__ by human liver microsomes. 2For a 15‐point nortriptyline (NT) formation rate vs substrate (AMI) concentration curve, a two enzyme model, consisting of one enzyme with MM kinetics (__V__~max~=1.2 nmol min^−1^ mg^−1^, __K__~__m__~=24 μm) together with a sigmoidal component (described by an equation equivalent to the Hill equation for cooperative substrate binding; __V__~max~=2.1 nmol min^−1^ mg^−1^, __K__′=70 μm; Hill expone

Who reads Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation?

Author

JÜRGEN SCHMIDER; DAVID J. GREENBLATT; JEROLD S. HARMATZ; RICHARD I. SHADER

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley; Research Square (ISSN 0306-5251)

Published

1996

Language

EN

Field

Medicine (Health Sciences)