conjugation

Conjugation is the body's way of 'wrapping' a drug so it can be thrown out. Imagine sticking a heavy, water-loving handle onto a slippery molecule: suddenly it is bulky and polar enough that the kidneys or bile can grab it and remove it.

In pharmacology, conjugation is the central type of phase II metabolism. An enzyme links the drug — or a phase I metabolite — to a naturally occurring endogenous molecule such as glucuronic acid, sulfate, glutathione, an acetyl group, a methyl group, or an amino acid. Each pathway uses its own transferase enzyme and a high-energy donor cofactor.

Conjugates are usually much more water-soluble and pharmacologically inactive, making conjugation a reliable route to elimination. Still, the supply of cofactors can be limited, so conjugation pathways can be saturated, and a small number of conjugates retain activity or, like reactive acyl glucuronides, can occasionally cause harm.