Xenobiotics are molecules that are not produced in vivo, but rather, are introduced into the body from the environment and subsequently metabolized by the body. Routes of introduction to the body include inhalation (e.g. aromatic hydrocarbons in cigarette smoke), intravenous (e.g. various anesthetics), transdermal and, for most pharmaceutical agents, ingestion. The metabolism of xenobiotics in our environment is an important field of investigation. However, to minimize risk and optimize therapeutic benefits, it is critical that the metabolism of candidate pharmaceutical agents be elucidated, including identification and properties of key metabolites.
The metabolism of xenobiotic substances may be divided into two phases.
Phase I Reactions: Addition or unmasking of a functional polar group. This typically results in a relatively small increase in hydrophilicity and may cause metabolic activation. These include enzymes such as cytochrome P450, flavin-containing monooxygenases, alcohol dehydrogenase, hydrolases, epoxide hydrolase, and carboxyl esterases.
Phase II Reactions: Conjugation with a small hydrophilic endogenous substance - often, but not always, to a functional group provided by a Phase I reaction - thereby significantly increasing hydrophilicity and facilitating excretion. These enzymes and molecules consist of glutathione s-transferases, glutathione, sulfate, and glucuronic acid.
OBR provides a variety assay kits, antibodies, and purified proteins for studying Phase I and Phase II reactions.