2001 Volume 24 Issue 9 Pages 1064-1067
The metabolism of bisphenol A (BPA) was determined for 11 forms of human hepatic cytochromes P450 (CYPs) expressed in the yeast Saccharomyces cerevisiae and for human steroidogenic CYP17 expressed in Escherichia coli. Additionally, the effect of BPA on the progesterone 17α-hydroxylase activity of CYP17 was investigated. CYP2C18 catalyzed BPA metabolism most efficiently, followed by CYP2C19 and CYP2C9. CYP2C9 and CYP2C18 exhibited the highest affinity (Km=3.9 μM) for BPA metabolism. The Vmax of CYP2C18 (8.10 nmol · min-1 · nmol CYP-1) was 5 times higher than that of CYP2C9. Although the Vmax of CYP2C19 was 1.5 times higher than that of CYP2C18, the affinity of CYP2C19 was 12 times lower than that of CYP2C9 and CYP2C18. Therefore the intrinsic elearance (Vmax/Km) of CYP2C18 was more than 5 times higher than that of CYP2C9 and CYP2C19. On the other hand, BPA exhibited a competitive-type inhibition of the progesterone 17α-hydroxylase activity of CYP17 with a Ki value of 71 μM, whereas no metabolism of BPA by CYP17 was detected. These results suggest that BPA is mainly metabolized by the CYP2C subfamily in human liver, and that BPA inhibits human steroidogenic CYP17 activities.