ABSTRACT
For an organism to eliminate a lipophilic, chemically inert xenobiotic, it is usually first necessary to oxidize it to a more polar form. In addition, many biosynthetic pathways that produce steroid hormones, prostaglandins, leukotrienes. involve oxidative steps. Oxidation can occur by addition of oxygen, removal of hydrogen atoms, or simply removal of electrons. This chapter begins with a discussion of the oxidative enzymes with examples of specific oxidations that each enzyme meditates. Out of all the metabolic enzymes involved in the oxidation of drugs, the cytochrome P450s are by far the most common and the most important. The P450s are moderately sized proteins having molecular weights that fall within the range of 48 to 53 kDa. The fact that so many substrates for CYP2D6 have the common structural feature of being organic bases is probably the reason that the particular cytochrome P450 was among the first human P450s whose active site was explored using the computer technique of homology modeling.
