conjugation

Conjugation in drug metabolism means the body grabs one of its own everyday molecules and chemically welds it onto a drug, like tying a heavy water-soluble anchor to something it wants to drag out. The point is to make the drug bulkier and far more soluble in water so it can be excreted.

Technically, conjugation reactions are the heart of phase II metabolism. An enzyme transfers an endogenous group — glucuronic acid, sulfate, glutathione, an acetyl group, an amino acid such as glycine, or a methyl group — from an activated cofactor onto a reactive site on the drug. Because cofactor supplies are finite, conjugation pathways can become saturated at high drug doses, changing how a drug behaves as the dose rises.

Conjugation usually terminates a drug's action by adding polarity and abolishing target binding, sending the product toward urinary or biliary excretion. It is generally a detoxifying step, but it is not universally benign: glutathione conjugation is the body's main defense against reactive electrophiles, whereas certain reactive conjugates can themselves contribute to toxicity.