Conjugation

Conjugation refers to the phase II metabolic process of (enzymatic) addition of a large, usually water-soluble group onto an appropriate functional group (e.g. hydroxyl) on a drug or a phase I metabolite. The group (often a sugar or sulphate) is transferred from a large, high-energy carrier molecule by a conjugating enzyme. The conjugate is then eliminated either in the urine or is secreted in bile (usually for conjugates with molecular weights over 400 g/mol) and eliminated in the faeces.

Conjugation is usually designed to convert a lipophilic drug that is difficult to eliminate into a more hydrophilic metabolite that is easier to eliminate. This is true for sugar conjugation (glucuronidation) and sulphate conjugation (sulphation) but less so for N-acetylation, where conjugates may be less water-soluble than the parent drug. Conjugation with glutathione is a detoxification process that renders harmful electrophilic species such as the acetaminophen metabolite, NAPQI, non-toxic. If conjugation is carried out on a parent drug, then the conjugation process would contribute to the hepatic clearance for that drug.