Biotransformation of BPA via epoxidation catalyzed by Cytochrome P450

Abstract

Metabolites formed during the biotransformation mediated by CYP450 may turn toxic. Investigations upon the mechanism involved in the formation of such toxic byproducts are important in analyzing their potential threat and also in elucidating the pathway for their removal. Bisphenols belong to the class of omnipresent phytochemicals. Eventually this leads to their higher exposure to humans. Therefore, preventions for the toxicity in BPA (2, 2-bis (4-hydroxyphenyl propane) has been of utmost priority. However, the mechanisms involved in their biotransformation are still a domain of topical interest.Since, epoxides are not commonly found in nature and are usually produced due to interaction of alkenes or olefins from CYP450. In the present article, efforts have been made to investigate the toxicity and mechanism involved in the formation of epoxide intermediate of bisphenol catalyzed through CYP450. Theoretical methods are utilized to investigate the mechanism, involved energetics, electronic reorganizations, structural information, barrier heights and DFT descriptors of the reactant & product, during the course of the reaction to elucidate the formation of epoxide product. The reaction mechanism was found to be stepwise and prefers low spin surface in the epoxidation process. Also, the epoxide metabolite formed after epoxidation was found to be more toxic than the parent compound.