Premium
Differential inhibition of aflatoxin B1 oxidation by gestodene action on human liver microsomes
Author(s) -
Kim Bok Ryang,
Oh Hyun Sook,
Kim DongHyun
Publication year - 1997
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549700204651
Subject(s) - gestodene , hydroxylation , microsome , chemistry , cytochrome p450 , aflatoxin , epoxide , biochemistry , stereochemistry , metabolism , enzyme , population , food science , demography , sociology , family planning , research methodology , catalysis
Human cytochrome P450 (P450) 3A is known to be involved in the formation of both aflatoxin B1‐exo‐8,9‐epoxide (exo‐epoxidation) and aflatoxin Q1 (3α‐hydroxylation). Gestodene, a known inactivator of P450 3A4, inhibited the formation of AFB1 metabolites in a variety of ways depending on the incubation condition. Preincubation of gestodene with human liver microsomes prior to the addition of AFB1 inhibited both exo‐epoxidation and 3α‐hydroxylation whereas simultaneous incubation of gestodene with AFB1 only inhibited 3α‐hydroxylation. These results suggest that two independent substrate binding sites exist in P450 3A4, and AFB1 binds to both of the binding sites. Gestodene selectively binds to one of the binding sites leading to the formation of AFQ1, whereas it does not affect the formation of exo‐epoxide via the other binding site.