Hepatic microsomal drug-metabolizing enzymes (DMEs)

Hepatic microsomal drug-metabolizing enzymes are a diverse group of proteins located within the smooth endoplasmic reticulum of hepatocytes that facilitate the biotransformation of drugs and other xenobiotics. This system primarily includes the Cytochrome P450 (CYP) superfamily, flavin-containing monooxygenases (FMOs), and UDP-glucuronosyltransferases (UGTs) (Zanger & Schwab, 2013). These enzymes play a dual role: they detoxify lipophilic compounds by increasing their water solubility for excretion and, in some cases, activate prodrugs into their pharmacologically active forms (Guengerich, 2008). While they are not typically the intended therapeutic targets of drugs, their activity is a critical determinant of drug clearance, half-life, and overall bioavailability (FDA, 2020). Modulation of these enzymes through induction or inhibition is a major source of drug-drug interactions, which can lead to therapeutic failure or toxicity (StatPearls, 2023). Furthermore, genetic polymorphisms in these enzymes are a primary cause of inter-individual variability in drug response, making them central to the field of pharmacogenomics.

Other names

Drug-metabolizing enzymes in liver microsomesMicrosomal drug-metabolizing enzymesHepatic microsomal enzymesMixed-function oxidasesPhase I and II enzymesLiver microsomes

Metabolic conversion of lipophilic drugs into polar metabolites for excretion; activation of prodrugs; inhibition or induction of enzyme activity leading to altered drug exposure.