Cytochrome P450 oxidations in the generation of reactive electrophiles: epoxidation and related reactions

Much of the interest in the cytochrome P450 (P450) enzymes has been because of oxidation of chemicals to reactive products. The epoxides (oxiranes) have been a major topic of interest with olefins and aryl compounds. Epoxides vary considerably in their reactivity, with t1/2 varying from 1 s to several hours. The stability and reactivity influences not only the overall damage to biological systems but also the site of injury. Transformations of some xenobiotic chemicals may involve products other than epoxides. Chemicals considered here include olefins, aromatic hydrocarbons, heterocycles, vinyl halides, ethyl carbamate, vinyl nitrosamines, and aflatoxin B1. These compounds either are unsaturated or are transformed to unsaturated products. The epoxides and other products provide a view of the landscape of P450-generated reactive products and the myriad of chemistry involved in the metabolism of drugs and protoxicants. Understanding the chemical nature of reactive products is necessary to develop rational strategies for intervention.