Recent Studies on the Structure and Function of Multisubstrate Flavin-Containing Monooxygenases

Interest in the oxidation of xenobiotics catalyzed by flavin-containing monooxygenases has expanded dramatically over the past decade. Studies on their exceptional substrate range, wide tissue distribution, and the existence of multiple forms are perhaps the major developments that have stimulated recent work on these enzymes. In addition, the reports by Smith and his associates on the polymorphism of the N-oxygenation of trimethylamine (1) and nicotine (2) in humans apparently due to a genetic defect in one or more of the flavin-containing monooxygenases has fueled further interest in the role of these enzymes in the metabolism of xenobiotics. This review focuses primarily on recent work on the number of isoforms (based largely on differences in primary structures deduced from cDNAs) present in major organs of entry, possible methods for estimating substrate specificity and activity of different isoforms in crude tissue preparations, and methods for manipUlating hepatic concentration (activity) of flavin-containing monooxygenases with dietary xenobiotics. The latter work, while still in very early stages, will undoubtedly have a significant impact on this area of drug metabolism by providing a convenient model for assessing the effect of changes in the concentration of these enzymes on the metabolism of a specific