Abstract
The metabolism of xenobiotics is thought to occur in two phases: phase I (preconjugation) and phase II (conjugation) (Williams, 1960). The present study is concerned with various aspects of phase I metabolism and this aspect, therefore, will be given particular attention. The commonest phase I reactions in xenobiotic metabolism are oxidative, and may be visualised as hydroxylations (Gillette, I966); see Figure 1.1. The system bringing about hydroxylation has been termed a mixed function oxidase (Mason, 1957), since in the course of the reaction one oxygen atom of molecular oxygen is incorporated into the substrate and the other is used to form water. In the majority of cases, the above reactions occur in the liver endoplasmic reticulum by means of a haemoprotein (CO binding pigment) termed cytochrome P450 (Coon et al, 1973; Estabrook, 1973). Cytochrome P450 has a tetrapyrrole prosthetic group containing ionic iron (termed protohaem) either in the ferrous (Fe++) or ferric (Fe+++) state, while the four nitrogen atoms of the tetrapyrrole are considered to bind to the iron. This complex is believed to be associated with microsomal lipoprotein.