Drug Metabolism: Other Phase I Enzymes

To this date, most of the scientific literature related to drug metabolism has focused on the characterization of cytochrome P450-mediated processes, with the other phase I drug metabolizing enzymes largely overlooked. However, an increasing volume of recent studies have highlighted the important contribution of non-P450 human drug-metabolizing enzymes in converting drugs/pro-drugs into either more hydrophilic compounds, non-toxic excretable metabolites or activated drugs. Based on these new data, this chapter presents the current state of the art of other Phase I drug metabolizing enzymes by reviewing a selected group of these enzymes. Special attention is devoted to flavin-containing monooxygenases (FMOs), for which new interesting data have become available concerning their structural features, their overall catalytic mechanism, as well as the effect of polymorphisms on their activity. In addition to FMOs, four other phase I drug metabolizing enzymes are also briefly reviewed including aldehyde oxidases, aldehyde dehydrogenases, alcohol dehydrogenases and carboxylesterases. For each of these enzymes the catalytic mechanism is presented together with information on their specific role in drug metabolism and the available kinetic data for the metabolism of drugs. The resulting content of this chapter aims at becoming a source of relevant information as well as elaboration of data for these highly relevant enzymes.