In subsequent phase II reactions, these activated xenobiotic metabolites are conjugated with charged species such as glutathione (GSH), sulfate, glycine, or glucuronic acid. Sites on drugs where conjugation reactions occur include carboxy (-COOH), hydroxy (-OH), amino (NH), and thiol (-SH) groups. Products of conjugation reactions have increased  molecular weight and tend to be less active than their substrates, unlike Phase I reactions which often produce active metabolites. The addition of large anionic groups (such as GSH) detoxifies reactive electrophiles and produces more polar metabolites that cannot diffuse across membranes, and may, therefore, be actively transported.
These reactions are catalysed by a large group of broad-specificity transferases, which in combination can metabolise almost any hydrophobic compound that contains nucleophilic or electrophilic groups. One of the most important classes of this group is that of the glutathione S-transferases (GSTs).