Drug Metabolism in Drug Design and Development Basic Concepts and Practice
portion of the profile that occurs at higher substrate concentrations. In this case, CLintis the ratio ofVmax2/Km2but since the ...
researchers have incorrectly fit these types of data by either ignoring (and thus, omitting) the data points after the apex in w ...
phenomenon is thought to occur due to simultaneous binding of both substrate and effector molecule within the enzyme active site ...
heteroactivation, as well as additional parameters that shed light into the changes that have occurred in the enzyme kinetics. v ...
activity remains, even at saturating concentrations of the inhibitor, and thus partial inhibition is observed. This partial inhi ...
both substrate and inhibitor are competing for the enzyme active site and their binding is mutually exclusive. When the inhibito ...
enzyme–inhibitor complex that can subsequently dissociate to form an enzyme–substrate complex that can undergo catalysis to prod ...
inhibition to occur, one would have to imagine a situation in which the inhibitor affected the catalytic properties of the enzym ...
4.7.6 Summary of Effects of Various Inhibition Types of Kinetic Parameters A summary of the effects onKmandVmaxresulting from th ...
for a quick estimation of the inhibition parameters but also to help determine the type of inhibition that is occurring. Sometim ...
4.9 Mechanism-Based Enzyme Inactivation Kinetics Mechanism-based enzyme inactivation kinetics refers to the irreversible inhibit ...
suicide inactivation, enzyme-activated irreversible inhibition and other terms. An excellent primer on mechanism-based enzyme in ...
of the criteria here as they are covered extensively in the above reference. In addition, the reader is encouraged to consult th ...
References Cornish-Bowden A. A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non- ...
Shou M, Grogan J, Mancewicz JA, Krausz KW, Gonzalez FJ, Gelboin HV, Korzekwa KR. Activation of CYP3A4: Evidence for the simultan ...
5 Metabolism-Mediated Drug–Drug Interactions HONGJIANZHANG,MICHAELW. SINZ,ANDA. DAVIDRODRIGUES 5.1 INTRODUCTION Serious drug–dru ...
on the cytochrome P450 (CYP) family of enzymes, many of the same concepts more or less apply equally to other enzymes (e.g., non ...
TABLE 5.1 Types of inhibition (when catalysis conforms to Michaelis–Menten kinetics) a. Reversible Mode of inhibitor binding Kin ...
dialysis of the incubate, a suitable (1 : 1) stoichiometry of radioactively labeled inactivator to active site, and a demonstrab ...
degrees of success (Table 5.2). General assumptions underpinning in vivo predictions usingin vitrodata include (1) liver is the ...
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