Fig. 5. Proposed model for apparent non-competitive inhibition of P450 3A4 oxidation activities by the substrate cholesterol (
Segel, 1975;
Shinkyo and Guengerich, 2011): E, P450 3A4; I, cholesterol; S, substrate; EI, P450 3A4-cholesterol complex; EI´, P450 3A4-cholesterol complex catalyzing cholesterol 4β-hydroxylation; ES, P450 3A4-substrate complex; ESI, P450 3A4-substrate-cholesterol complex. Reprinted from J. Biol. Chem., Vol. 286, Shinkyo, R. and Guengerich, F. P., Inhibition of human cytochrome P450 3A4 by cholesterol, pages 18426-18433 (
Shinkyo and Guengerich, 2011), Copyright (2011), with permission from Elsevier.
