Drug metabolism and enzyme induction

Abstract

The prediction of metabolism-dependent toxicity is a cutting-edge topic in toxicology (Bolt and Hengstler, 2008). The shape of dose-response curves and toxic profiles are strongly dependent on activating or detoxifying metabolism. Most xenobiotic metabolizing enzymes include large numbers of isoenzymes with distinct substrate specificities. This diversity started to evolve 200 to 400 million years ago when reptiles and amphibians moved from sea to land and began to eat plants. The resulting co-evolution led to the establishment of phytotoxins which gave plants protection against herbivores, and herbivores responded with new detoxifying enzymes. A highlight in our partner journal is the initiation of a new series of review articles discussing nomenclature of isoenzyme families, genetic organization, polymorphisms, substrate specificities, clinical relevance and a role in carcinogenesis (Mates et al., 2008; Florl and Schulz, 2008; Strassburg et al., 2008; Beyersmann and Hartwig, 2008; Pelkonen et al., 2008; Verstraeten et al., 2008; Adam and Laufs, 2008). To give our readers an overview we summarize the key messages of articles on drug metabolism (Table 1A) and enzyme induction (Table 1B).