chapter  9
26 Pages

Effect of Cytokines on Drug-Metabolizing Enzymes

ByMichael J. Myers, Joseph C. Kawalek

The microsomal mixed-function oxidase system is the major oxidative pathway used for the metabolism of most xenobiotics and many endogenous compounds. As such, it plays a crucial role in the inactivation or detoxification of the various lipophilic compounds such as drugs and steroids. It is also responsible for the activation of environmental toxicants and carcinogens. The terminal oxidase of this system is called cytochrome P450 (P450) (1). This hemoprotein is actually a group of isozymic proteins, all of which function by binding a lipophilic substrate and molecular oxygen resulting in the insertion of a hydroxyl group into the substrate. The various P450 hemoproteins have been organized on the basis of their DNA sequences into gene families (2,3). To a certain extent, this system groups the various cytochrome P450 enzymes into clusters that have similar, but not necessarily the same, substrate specificities.236