Conjugation, a key component of phase II biotransformation reactions, is a vital process in drug detoxification. It involves transferring endogenous substances like glucuronic acid, sulfate, and glycine to drugs or their metabolites formed in phase I reactions. These conjugation reactions, often catalyzed by specific enzymes, transform potentially harmful metabolites into inactive, water-soluble forms easily excreted in urine or bile. By enhancing polarity and eliminating pharmacological activity, conjugation effectively ends drug action and facilitates safe excretion. Phase I reactions often prepare molecules for this process by introducing functional groups, making conjugation a crucial step in comprehensive drug metabolism.
Conjugation reactions are highly specific, occurring between distinct functional groups on the drug or metabolite and the conjugating agent. These agents, such as glucuronic acid and sulfate, are abundant in the body, making them readily available for these reactions. The capacity for conjugation varies among different drugs and functional groups, with some drugs being more prone to conjugation than others. The formation of conjugates through phase II reactions significantly increases their molecular weight, boosting their water solubility and facilitating their excretion. Conjugates are typically expelled from the body through renal excretion via urine or biliary excretion via bile.
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