Metabolism of Toxicants

One of the most important determinants of xenobiotic persistence in the body and subsequent toxicity to the organism is the extent to which they can be metabolized and excreted. Several families of metabolic enzymes are involved in xenobiotic metabolism. Phase I enzymes, which typically add a polar reactive group to the xenobiotic, include the cytochrome P450 monooxygenases (CYPs), flavin containing monooxygenases (FMOs), alcohol and aldehyde dehydrogenases, amine oxidases, cyclooxygenases, reductases, and hydrolases. Phase II enzymes, which often utilize phase I metabolites as substrates, include a variety of conjugating enzymes such as glucuronidases, sulfotransferases, methyltransferases, glutathione transferases and acetyl transferases. Examples of the metabolic transformations each of these enzyme groups performs on classical substrates are provided along with a brief summary of the current state of knowledge about the family of enzymes described.