Testosterone, CYP3A4 interactions

Figure 22 Examples of enzyme kinetic plots used for determination of Km and Vmax for a normal and an allosteric enzyme Direct plot [(substrate) vs. initial rate of product formation] and various transformations of the direct plot (i.e., Eadie-Hofstee, Lineweaver-Burk, and/or Hill plots) are depicted for an enzyme exhibiting traditional Michaelis-Menten kinetics (coumarin 7-hydroxylation by CYP2A6) and one exhibiting allosteric substrate activation (testosterone 6(3-hydroxylation by CYP3A4/5). The latter exhibits an S-shaped direct plot and a hook -shaped Eadie-Hofstee plot such plots are frequently observed with CYP3A4 substrates. Km and Vmax are Michaelis-Menten kinetic constants for enzymes. K is a constant that incorporates the interaction with the two (or more) binding sites but that is not equal to the substrate concentration that results in half-maximal velocity, and the symbol n (the Hill coefficient) theoretically refers to the number of binding sites. See the sec. III.C.3 for additional details.

Galetin A, Clarke SE, Houston JB. Multisite kinetic analysis of interactions between prototypical CYP3A4 subgroup substrates midazolam, testosterone and nifedipine. Drug Metab Dispos 2003 31 1108-1116. 

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