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Phase II drug metabolizing enzyme

Molecular classification
Enzyme, Transferase, Other (composite functional group, not a single molecular entity)
01

Overview

Phase II drug metabolizing enzymes comprise a group of broad-specificity conjugating enzymes, mainly transferases, that add polar endogenous groups (such as glucuronic acid, sulfate, acetyl, methyl, and glutathione) to drugs, xenobiotics, or endogenous toxic compounds, rendering them more hydrophilic and readily excretable. The primary families include UDP-glucuronosyltransferases, sulfotransferases, N-acetyltransferases, glutathione S-transferases, and methyltransferases. These enzymes are essential for the detoxification and clearance of both endogenous and exogenous substrates. Genetic polymorphisms in several phase II enzymes (e.g., NAT2, GSTs) can significantly influence individual responses to drugs and susceptibility to some diseases, such as certain cancers and drug toxicities. "Phase II enzyme" is not a single molecular target or protein, but rather an umbrella term for many specific enzymes with related—though distinct—functions[1][2][3][5][4][6].

Other names
Phase II enzymesconjugation enzymesphase II DMEsdrug conjugating enzymestransferases (includes distinct enzyme families: UDP-glucuronosyltransferase, sulfotransferase, N-acetyltransferase, glutathione S-transferase, methyltransferase)
02

Mechanism of action

Conjugation/inactivation (through glucuronidation, sulfation, acetylation, methylation, glutathione conjugation); Polymorphic metabolism (variability due to genetics leading to increased/decreased drug levels)

03

Biological functions

Drug metabolismMetabolic detoxificationXenobiotic conjugationBiotransformation of endogenous compounds
04

Disease associations

CancerInherited metabolic disordersDrug hypersensitivity/toxicityOther
05

Safety considerations

Adverse drug reactions due to polymorphisms (e.g., slow acetylators at risk for toxicity)Drug inefficacy or increased toxicity from altered metabolismInter-individual and inter-ethnic variation in enzyme activity
06

Interacting drugs

Isoniazid (target of N-acetyltransferases)

6 more in the full profile.

07

Biomarkers

NAT2 acetylator phenotype (for isoniazid, hydralazine sensitivity)GSTM1 and GSTT1 gene deletion (susceptibility to detoxification issues, some cancers)

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