Xenobiotic Detoxification

Key points

• • Detoxification (biotransformation) happens mainly in the liver and converts fat-soluble foreign compounds into more water-soluble forms that the kidney can excrete.
• • Phase I reactions add or expose a reactive chemical group, usually by oxidation carried out by the cytochrome P450 enzyme family in the smooth endoplasmic reticulum.
• • Phase II reactions then attach a water-soluble molecule (conjugation), such as glucuronic acid, sulfate, glutathione or an amino acid, making the product easy to excrete.
• • Phase I can sometimes create a product that is more reactive or toxic than the original, which is then made safe by phase II conjugation.
• • Glucuronidation, the addition of glucuronic acid, is a major phase II route and is used for bilirubin as well as for many foreign compounds.
• • Because many compounds share the cytochrome P450 enzymes, one substance can speed up or slow down the breakdown of another, the basis of many drug interactions.