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Drug-metabolizing enzyme (DME)
- Target
- DME
- Molecular classification
- Enzyme, Oxidoreductase (for some, e.g., cytochrome P450 family), Transferase (e.g., UDP-glucuronosyltransferase, sulfotransferase), Hydrolase (e.g., esterases)
01
Overview
Drug-metabolizing enzymes are a collection of primarily hepatic enzymes that chemically modify drugs and xenobiotics through a series of reactions classified as Phase I (e.g., oxidation, reduction, hydrolysis via cytochrome P450, flavin monooxygenases, esterases) and Phase II (conjugation via UDP-glucuronosyltransferase, sulfotransferase, acetyltransferase). These enzymes determine the rate and mechanism of drug elimination, impact patient response through genetic variability, and constitute key determinants in drug-drug interactions, efficacy, and toxicity. Their activity plays essential roles in both therapeutic success and risks, influencing treatment outcomes and supporting personalized medicine approaches.
- Other names
- Drug metabolism enzymeXenobiotic metabolizing enzymeDMEPhase I enzymePhase II enzyme
02
Mechanism of action
Drug oxidation (CYP450-dependent) Drug reduction Hydrolysis of esters/amides Drug conjugation (e.g., glucuronidation, sulfation, acetylation) Inhibition/Induction by co-administered drugs, affecting metabolism rates
03
Biological functions
Biotransformation (oxidation, reduction, hydrolysis, conjugation)DetoxificationDrug metabolismMetabolic activation (sometimes converting prodrugs or environmental carcinogens into active forms)Maintenance of homeostasis for endogenous compounds
04
Disease associations
Cancer (activation or detoxification of carcinogens)Drug toxicity/adverse drug reactionsMultidrug resistancePharmacogenetic syndromes (due to enzyme polymorphisms)Other, e.g., influence on cardiovascular/neurological drug response
05
Safety considerations
Drug-drug interactions due to enzyme inhibition or inductionToxicity from accumulation or metabolic activation of drugsGenetic polymorphisms causing variable drug response (poor, intermediate, extensive, ultra-rapid metabolizers)Risk of carcinogenesis due to activation of procarcinogens
06
Interacting drugs
Statins
8 more in the full profile.
07
Biomarkers
CYP2D6 genotype (used for patient selection, dosing for many psychoactives and opioids)CYP2C19 genotype (used for clopidogrel efficacy)CYP2C9 genotype (used for warfarin dosing)Specific DME activity measurements (phenotyping for metabolic status)
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