Phase II detoxification enzyme

Phase II detoxification enzymes are a diverse group of transferases responsible for catalyzing conjugating reactions that attach hydrophilic groups—such as glucuronic acid, sulfate, acetyl groups, methyl groups or glutathione—to reactive metabolites produced during phase I metabolism. This process increases solubility and facilitates excretion via urine or bile while reducing toxicity. Major families include UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), N-acetyltransferases (NATs), glutathione S-transferases (GSTs), and various methyltransferases. These enzymes play critical roles in protecting cells from damage caused by xenobiotics—including drugs—and endogenous waste products but also influence individual responses to medications based on genetic variation.[2][3] Overexpression can contribute to therapy resistance in cancer; deficiencies increase susceptibility to toxic effects from certain exposures.[1]

Other names

Phase II metabolic enzymeConjugation enzymeDrug-metabolizing transferase (includes specific types like UGTs, GSTs)Biotransformation enzyme (Phase II)

Drugs targeting these enzymes may act as substrates for conjugation reactions—rendering them more water-soluble for excretion—or as inhibitors/inducers affecting the rate of metabolism. Some dietary components can induce expression via activation of transcription factors such as Nrf2; others may inhibit activity directly or through competitive substrate binding[1][6].