PHAR 315 Lecture Notes - Lecture 6: Flavones, Uncompetitive Inhibitor, Cyp3A4
23 Feb 2016
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Some in-vitro kinetics do not follow the classic hyperbola described by the m-m equations (see last page) Of particular importance are: autoactivation: results in an initial lag in the rate-[substrate] profile = sigmoidal kinetics, autoinhibition: characterized by a convex curve due to vmax not being maintained at high substrate concentrations = substrate inhibition kinetics. The problem with m-m is that it assumes that substrate-enzymes interactions occur at only one site per enzyme, and that each site acts independently: we know that for sure cyp3a4 does not act this way! Using equations to describe sigmoidal and substrate inhibition kinetics: The sigmoidal rate plot (a) is described using the hill model: S50 = [substrate] resulting in of vmax (analogous to km of m-m kinetics) n = the hill coefficient. When a is translated to a clearance plot (e) the curve can be described:
