phase II metabolism

If phase I bolts a handle onto a drug, phase II uses that handle to attach a large, water-loving tag — like sticking a postage label on a parcel so the body can mail it out. These conjugation reactions are the body's main way of turning lipophilic compounds into highly water-soluble ones that the kidneys or bile can readily excrete.

In a phase II reaction, an enzyme transfers a bulky polar group from an activated donor onto the drug. Common conjugations include glucuronidation (adding glucuronic acid via UGT enzymes), sulfation, glutathione conjugation, acetylation, and methylation. The added group sharply increases water solubility and usually abolishes pharmacological activity, marking the molecule for elimination.

Phase II generally yields safer, more polar, inactive products, which is why it is often called the detoxification phase. There are honest exceptions, though: glutathione conjugation specifically mops up reactive electrophiles before they harm cells, while a few acyl glucuronides are themselves chemically reactive. Phase II can also occur without any preceding phase I step if the drug already carries a suitable functional group.