In phase II reactions, parent drugs or phase I metabolites, bearing suitable functional groups, react with endogenous molecules to produce more hydrophilic drug conjugates. The two main conjugation reactions, sulfation and glucuronidation, often generate biologically inactive metabolites. However, in the case of certain prodrugs, active metabolites may be formed. Glucuronidation occurs at the luminal side of the endoplasmic reticulum. The reaction involves an activated high-energy endogenous cofactor, from which glucuronic acid gets transferred to the reactive functional group on the substrate in the presence of UDP-glucuronyl transferase. The metabolites produced have high molecular weights and are therefore excreted in bile. Sulfation occurs in the cytosol. The reaction involves the formation of an active endogenous cofactor, phosphoadenosyl phosphosulfate, which transfers a sulfate group to the reactive handle on the substrate in the presence of the sulfotransferase enzyme.